Leukemia Committee Agenda 2003/Leukemia.pdf · Dr. Schiffer Proposed Studies S0106 A Phase III Study of the Addition of Gemtuzumab Ozogamicin (Mylotarg™) During Induction Therapy

LEUKEMIA COMMITTEE

Chair: Frederick R. Appelbaum, M.D. Vice Chair: David R. Head, M.D.

Statisticians: Kenneth J. Kopecky, Ph.D.

Holly Gundacker, M.S.

Data Coordinator: Laura Kingsbury, M.R.T. Protocol Coordinator: Larissa Rios, B.A.

Pathology: David R. Head, M.D.

Cytogenetics Liaison: Marilyn L. Slovak, Ph.D.

Nurse: Rose B. Ermete, R.N., O.C.N.

Clinical Research Associates:

Emilia G. Cantu, B.A. Connie Sparks, C.R.A. Gaye L. Winakur, C.C.R.A.

APRIL 10 - 13, 2003 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 1

CONTENTS Leukemia Committee Agenda..................................................................................... 3

Initial Registrations to Therapeutic Studies................................................................. 5

Patient Registration by Study and Arm ....................................................................... 6

S9007 Biologic Intergroup .......................................................................................... 7

S9910 Biologic............................................................................................................ 9

S0010 Phase II........................................................................................................... 11

S0020 Phase II........................................................................................................... 14

S0106 Phase III ......................................................................................................... 17

S0112 Phase II........................................................................................................... 19

S0117 Phase II........................................................................................................... 23

S0125 Phase II........................................................................................................... 24

C9710 Phase III Intergroup ....................................................................................... 25

E2997 Phase III Intergroup ....................................................................................... 27

2 LEUKEMIA SOUTHWEST ONCOLOGY GROUP APRIL 10 - 13, 2003

Leukemia Committee Agenda

Introductory Remarks

Current Status of the Leukemia Committee Dr. Appelbaum

Status of AML/MDS Studies

Active and Closed Studies

C9710 Phase III Randomized Study of Concurrent Tretinoin and Che-motherapy with or without Arsenic Trioxide (As2O3) (NSC #706363) as Initial Consolidation Therapy Followed by Mainte-nance Therapy with Intermittent Tretinoin Versus Intermittent Tretinoin Plus Mercaptopurine and Methotrexate for Patients with Untreated Acute Promyelocytic Leukemia.

Dr. Coutre

S0112 A Phase II Study of Daunomycin and Ara-C, Both Given by Continuous IV Infusion for Previously Untreated Non-M3 Acute Myeloid Leukemia (AML) in Patients of Age 56 or Older.

Dr. Chauncey

S0020 A Phase II Study of Anti-Thymocyte Globulin and Cyclosporine for Patients with Myelodysplastic Syndrome (MDS). Dr. Schiffer

Proposed Studies

S0106 A Phase III Study of the Addition of Gemtuzumab Ozogamicin (Mylotarg™) During Induction Therapy and Post-Consolidation Therapy Versus Standard Induction and Consolidation Therapy with Daunomycin and Cytosine Arabinoside for Patients Under Age 56 with de novo Acute Myeloid Leukemia (AML)

Dr. Petersdorf

S0117 A Phase II Study of Gemtuzumab Ozogamicin (MylotargTM) and Standard Dose Ara-C for Patients with Relapsed Acute Myeloid Leukemia (AML).

Dr. Godwin

S0125 A Phase II Study of Chimerism-Mediated Immunotherapy (CMI) Using Nonmyeloablative Allogeneic Transplantation in Older Patients with Acute Myeloid Leukemia (AML) in First Complete Remission.

Dr. McSweeney

S0301 A Phase II Study of Induction with Daunorubicin, Cytoarabine, and Cyclosporine, all by Continuous IV, for Previously Un-treated Non-M3 Acute Myeloid Leukemia (AML) in Patients of Age 56 or Older.

Dr. Chauncey

Status of CML Studies

Proposed Studies

S0325 Frontline CML with Gleevec. Dr. Drucker


Status of ALL Studies


S0010 A Phase II Trial of 506U78 (IND 52611) in Patients with Re-lapsed or Refractory Non T-Cell Acute Lymphoblastic Leukemia (ALL).

Dr. Coutre

Proposed Studies

S0321 Phase II Trial of T-Cell Relapsed ALL with Depsipeptide Dr. Godwin

C10001 A Phase II Trial of Sequential Chemotherapy, Imatinib Mesylate (Gleevec, STI571) (NSC #716051, IND #61135), and Transplan-tation for Adults with Newly Diagnosed Ph+ Acute Lymphoblas-tic Leukemia by the CALGB and SWOG.

Drs. Appelbaum and Radich

A Phase II Study of Two Remission Induction and Consolidation Regimens for Newly Diagnosed Adult Acute Lymphoblastic Leukemia..

Dr. Forman

Status of CLL Studies


E2997 Phase III Randomized Trial of Fludarabine and Cyclophospa-mide Versus Fludarabine for Previously Untreated Chronic Lymphocytic Leukemia.

Dr. Hussein

Proposed Studies

S0326 Phase II Trial of Relapsed CLL with Revimid. Dr. Hussein

Status of Other Studies


S9007 Cytogenetic Studies in Leukemia Patients. Dr. Slovak

S9910 Leukemia Centralized Reference Laboratories and Tissue Re-positories, Ancillary.

Dr. Willman


Initial Registrations to Therapeutic Studies by 12 Month Intervals

LEUKEMIA COMMITTEE

0

50

100

150

200

250

300

Time of registration

JAN 1997DEC 1997

145

41

87

4

JAN 1998DEC 1998

100

32

87

1

JAN 1999DEC 1999

32

11

27

JAN 2000DEC 2000

21

7

30

JAN 2001DEC 2001

188

34

JAN 2002DEC 2002

34

10

27

MEMBER AFFILIATES CCOP NON-SWOG


Patient Registration by Study and Arm LEUKEMIA COMMITTEE

July-Dec

2002 Jan-June 2002 July-Dec

2001 All Patients

S9007 Cytogenetic Studies in Leukemia Patients

Cytogenetics Sample 33 38 35 2,117 S9910 Leukemia Central Lab/Tissue Repository

Specimen Submission 31 35 32 169 S0010 Non-T-ALL, Rel/Refr., 506U78 506U78 2 4 4 16 S0020 MDS, ATG + Cyclosporine

ATG + Cyclosporine 7 3 4 14 S0112 AML, DNR/Ara-C cont infusion

DNR/Ara-C 17 22 11 50 C19801 T-ALL/LBL, Rel/Refr., 506U78 * 506U78 0 0 4 11 C9710 APL, ATRA +/- Arsenic Trioxide *

Induction/Consolidation 3 4 7 34 Induction/Consolidation w/Arsenic 3 5 6 29 6 9 13 63 E2997 CLL, FAMP+CTX vs FAMP alone *

Cyclophosphamide + Fludarabine 0 0 0 0 Fludarabine 1 0 0 1 1 0 0 1 E2998 AML, Remission, Flt3L vs Obs. *

Flt3L 0 0 1 2 Observation 0 0 0 1 0 0 1 3

* For non-SWOG coordinated studies only SWOG registrations are shown.


S9007 Biologic Intergroup Coordinating Group: SWOG

Cytogenetic Studies in Leukemia Patients

Intergroup Participants: SWOG, ECOG

Study Coordinators: M Slovak, E Paietta (ECOG)

Statisticians: H Gundacker, K Kopecky

Data Coordinator: L Kingsbury

Date Activated: 7/15/1991

Objectives To estimate the frequencies and prognostic sig-nificance of cytogenetic abnormalities in marrow or blood cells of leukemia patients prior to treat-ment on Southwest Oncology Group protocols and at various times in the course of their treat-ment.

To estimate correlations between the presence of cytogenetic features and of clinical, pathophysi-ological, cellular, or molecular characteristics in these patients.

To provide quality control for all SWOG cytoge-netic data.

Patient Population Patients must be registered to any SWOG leuke-mia protocol approved after January 1, 1990, in-cluding ECOG patients registered to S9300.

Summary Statement As of December 31, 2002, a total of 2,117 pa-tients were registered on this study. ECOG par-ticipated in this study from August 15, 1995 through April 8, 1998.


S9007/BIOLOGIC

Registration by Institution

Registrations ending December 31, 2002

Institutions Total Reg Institutions

Total Reg

Wichita CCOP 133 Cincinnati MC, U of 21 LSU-Shreveport 83 Columbia River CC OP

Oklahoma, Univ of 21

Loyola University 80 21 Ohio State U 76 Breslin Cancer Ctr/Henry Ford Hosp 20 Puget Sound 76 Montana CCOP 20 Columbus CCOP 63 St Francis/Stormont/Kansas, U of 20 City of Hope Med CtrWayne State Univ

62 Kaiser Foundatn Hosp/Davis, U of CA 19 59 Riverside Methodist/Ohio State U 17

Cleveland Clinic OH 52 Grand Rapids CCOP 15 Davis, U of CA 50 Michigan, U of 15 St Louis Universi tyHenry Ford Hosp

49 BAMC/WHMC 14 47 Kentucky, U of 14

Kansas City CC P OSt Louis CCOP

46 Oregon Hlth Sci Univ 14 43 Carilion Medical Ctr/Temple University 13

San Antonio, U of TX 41 ECOG 13 Arkansas, U of 36 Providence Hosp 13 Upstate Carolina 33 Sutter Hlth Wester /Davis, U of CA n

Temple University 13

Utah, U of 33 13 Arizona, U of 32 Allegheny CCOP 12 Atlanta Reg CCOP 32 Michael Reese Hosp/Oklahoma, Univ of 12 Dayton CCOP 31 Northwest CCOP 12 New Mexico, U of 30 Tulane Univ/San Antonio, U of TX 11 Central IL CCOP 29 Akron Gen Med Ctr/Cleveland Clinic OH 10 Colorado, U of 29 Aultman Hospital/Ohio State U 10 So Calif, U of 27 Hawaii CCOP, Univ of 10 South Alabama CCOP 25 Salem Hospital/Oregon Hlth Sci Univ 9 Stanford University/City of Hope Med Ctr 25 Texas Tech Univ/San Antonio, U of TX 9 Scott & White/TX A&M 24 Hawaii, U of 8 Mississippi, Univ of 23 Santa Rosa Mem Hosp/Davis, U of CA 8 Boston Univ Med Ctr 22 Thompson Ca Surv Ctr/San Antonio, U of TX 8 LSU-New Orleans CCOP 22 All Other Institutions 267 Virginia Mason CCOP 22 Total (171 Institutions) 2,117


S9007/BIOLOGIC

S9910 Biologic

Leukemia Centralized Reference Laboratories and Tissue Repositories, Ancillary

Study Coordinators: C Willman, D Boldt




Objectives To develop and apply laboratory assays for the rapid and precise diagnosis of leukemia patients and identify biologic, genetic, and molecular pa-rameters that distinguish different subtypes of human leukemia with differing responses to ther-apy.

To develop "risk-adapted" therapeutic approaches in which biologic, genetic, and molecular pa-rameters are used to target individual patients to tailored therapeutic regimens, or, to randomize and stratify patients to different treatment arms of a therapeutic trial.

To develop new automated and standardized laboratory methods for the detection and monitor-ing of therapeutic responsiveness and minimal re-sidual disease in leukemia patients and develop new clinical approaches to employ such data in therapeutic decision making and clinical trial de-sign.

To maintain and expand tissue repositories of highly characterized leukemia samples from uni-formly treated Southwest Oncology Group pa-tients to promote Intergroup and external funda-mental scientific collaborations and to perform continued critical prospective and retrospective correlative biologic studies.

To utilize scientific information generated from Intergroup and collaborative studies to assist the Leukemia Committee in the development of new and more effective treatment regimens.

Patient Population Patients must be registered on a SWOG treatment study for lymphoid leukemia (ALL or CLL), myeloid leukemia (AML or CML) or myelodys-plasia on or after the date of activation of this study.

Summary Statement As of December 31, 2002, 169 patients have been registered to this study.


S9910/BIOLOGIC




Total Reg

Wichita CCOP 31 Central IL CCOP 2 Columbus CCOP 14 Kansas City CCOP 2 Loyola University 11 Oregon Hlth Sci niv U

Providence Hos 2

Stanford University/City of Hope Med Ctr 10 pSt Louis CCOP

2 Puget Sound 7 2 LSU-Shreveport 6 Utah, U of 2 New Mexico BCCOP MArizona, U of

6 Wayne State Univ 2 5 Akron Gen Me Ctr/Cleveland Clinic OH d

Arkansas, U of 1

Davis, U of CA 5 1 Grand Rapids CCOP 5 Columbia River CCO P

Gulf Coast MBCCOP 1

San Antonio, U of X TAtlanta Reg CCOP

5 1 4 Hawaii CCOP, Univ of 1

Montana CCOP 4 Henry Ford Hosp 1 Rochester, Univ of 4 Michigan, U of 1 Sutter Hlth Western/Davis, U of CA 4 Scott & White CCOP 1 Cleveland Clinic OH 3 Scripps Clinic/City of Hope Med Ctr 1 Mississippi, Univ of 3 South Texas Onc/Hem/San Antonio, U of TX 1 Oakwood Hospital/Michigan, U of 3 Thompson Ca Surv Ctr/San Antonio, U of TX 1 Oklahoma, Univ of 3 Tulane University 1 Ozarks Reg CCOP 3 Wenatchee Valley/Puget Sound 1 St Louis University 3 Total (42 Institutions) 169 Upstate Carolina 3


S9910/BIOLOGIC

S0010 Phase II

A Phase II Trial of 506U78 (IND 52611) in Patients with Relapsed or Refractory Non T-Cell Acute Lymphoblastic Leukemia (ALL)

Study Coordinators: S Coutre, D Boldt, M Slovak, D Head




Objectives To test whether the complete remission rate in adult patients with relapsed or refractory non T-cell acute lymphoblastic leukemia (ALL) is suffi-ciently high following treatment with 506U78 to warrant further investigation.

To estimate the frequency and severity of toxici-ties associated with the dosing schedule of 506U78 outlined by this protocol.

To investigate in a preliminary manner the fre-quency and prognostic significance of multidrug resistance gene expression and function (meas-ured prior to treatment), and of cell cycle regula-tory gene abnormalities and minimal residual dis-ease detected by RT-PCR or multiparameter flow cytometry (measured during clinical remission), in patients with relapsed or refractory adult non T-cell ALL.

Patient Population Patients must have a prior morphologic diagnosis of acute lymphoblastic leukemia (ALL) with FAB class L1-L2 and be either refractory to a standard induction regimen or have relapsed fol-lowing successful prior induction therapy. Pa-tients must have evidence of non T-cell ALL in their blood or marrow, or in at least one extrame-dullary disease site.

Patients must have passed their 16th birthday and have a Zubrod performance status of 0-3. Patients must have adequate renal and hepatic function, must be negative for CNS involvement of ALL, and must not have neuropathy ≥ Grade 2.

Accrual Goals Initially, 20 eligible patients will be accrued. If fewer than two of these patients achieve CR then

the study will be closed. Otherwise, 15 additional eligible patients will be accrued for a total of 35 patients.

Summary Statement As of December 31, 2002, sixteen patients have been accrued to this study.

Two of the sixteen patients are currently listed as ineligible due to lack of documentation. Both are included in the following analysis. All sixteen pa-tients are off treatment. Four patients died while on treatment: all four of causes not related to treatment. Two patients refused protocol-directed second induction attempts, one was not offered the second induction attempt in error and one was taken off on day nine due to elevated WBC. The reason for termination of treatment is pending for two patients. In addition, four patients are off treatment due to toxicity: two due to infection, one due to neurotoxicity, and one due to a brain abscess.

Two of the sixteen patients have not been evalu-ated for toxicity due to institutional failure to submit any data. Among the fourteen patients who have been evaluated for toxicities, one has died due to congestive heart failure. This death, which occurred two months after the patient was removed from protocol treatment following a sin-gle cycle of therapy, is currently under review. No Grade 4 non-hematologic toxicities have been reported. Grade 3 non-hematologic toxicities were reported for seven patients: three with feb-rile neutropenia, one with infection, one with feb-rile neutropenia and infection, one with confu-sion, and one with confusion and memory loss.


S0010/II



Institutions Total Reg

Arizona, U of 4Stanford University/City of Hope Med Ctr 3New Mexico MBCCOP 2Wichita CCOP 2Arkansas, U of 1Hawaii CCOP, Univ of 1Kansas City CCOP 1Scripps Clinic/City of Hope Med Ctr 1South Texas Onc/Hem/San Antonio, U of TX 1Total (9 Institutions) 16

Registration, Eligibility, and Evaluability

Registrations ending December 31, 2002; Data as of February 11, 2003

506U78 506U78 NUMBER REGI TERED S INELIGIBLE

16 ELIGIBLE 14

2 Insufficient Documentation 2 TOXICITY ASSESSMENT Reversible 2 Evaluable 14

Patient Characteristics


506U78 506U78 (n=16) (n=16)

AGE RACE Median 33 .6

20 White 10 63%

Minimum .870

Black 1 6% Maximum .5 Asian 2 13% Pacific Islander 1 6% SEX

11

69% Native American 2 13%

Males Females 5 31% HISPA NIC Ye

5

31%

s

No 11 69%


S0010/II

Treatment Summary


506U78 NUMBER ON PROTOCOL TREATMENT 0

NUMBER OFF PROTOCOL TRE TMENTA REASON OFF TREATMENT

16

Treatment completed as planned 2 Toxicity or side effects 4 Refusal unrelated to toxicity 2 Progression/relapse 0 Death 4 Other - not protocol specified 2 Reason under review 2 MAJOR PROTOCOL DEVIATIONS 0

Number of Patients with a Given Type and Degree of Toxicity

Non-Hematologic Toxicities Only Toxicities with No Entries for Grades 3 to 5 Have Been Suppressed


506U78 (n=14)

Grade

TOXICITY ≤ 2 3 4 5 Confusion 12 2 0 0 Febrile neutropenia 10 4 0 0 Infection with 3-4 neutropenia 12 2 0 0 LVEF decrease/CHF 13 0 0 1 Memory loss 13 1 0 0 MAXIMUM GRADE ANY TOXICITYNumber

6 7 0 1


S0010/II

S0020 Phase II

A Phase II Study of Anti-Thymocyte Globulin and Cyclosporine for Patients with Myelodysplastic Syndrome (MDS)

Study Coordinators: C Schiffer, J Anderson, C Willman, M Slovak, D Head

Statisticians: K Kopecky, H Gundacker



Objectives To test whether immunosuppressive therapy with anti-thymocyte globulin (ATG) and cyclosporine is sufficiently effective with respect to response in myelodysplastic syndrome (MDS) to warrant further investigation in Phase III trials.

To estimate the frequency and severity of toxici-ties associated with this regimen.

To investigate in a preliminary manner the corre-lation of response to treatment with in vitro as-sessment of T-lymphocyte subsets.

Patient Population Patients must have a morphologically confirmed diagnosis of MDS in one of the following sub-classifications, refractory anemia (RA), refractory anemia with ring sideroblasts (RARS), refractory anemia with excess blasts (RAEB), and must be in the low, intermediate-1, or intermediate-2 IPSS risk category.

Patients must not have undergone bone marrow or stem cell transplant or received prior chemo-therapy as treatment for MDS. Prior treatment with cytokines, colony stimulating factors, erythropoietin, amifostine, or hydroxyurea is permitted. Patients who have received prior che-motherapy and/or radiation therapy for other ma-lignant disorders and in whom the MDS is felt to be secondary to the prior therapy are eligible for this study. Patients must have received transfu-sions of at least four units of red blood cells as supportive care for anemia during the 60 days be-fore registration.

Patients must have a Zubrod performance status of 0,1 or 2 and must be HIV negative.

Stratification/Descriptive Factors Patients will be stratified by FAB classification: RA vs RARS vs RAEB.

Accrual Goals The accrual goals for this study are 53 eligible patients with RA, 33 eligible patients with RARS, and 44 eligible patients with RAEB for a total of 130 eligible patients.

Summary Statement As of December 31, 2002, fourteen patients have been accrued to this study, five with RARS, six with RAEB, and three with RA.

Three patients are ineligible: one RARS patient due to prior malignancy within three years before registration, one RAEB patient with high IPSS risk, and another RAEB patient for whom re-quired prestudy specimens were not submitted. The latter RAEB patient is included in the follow-ing results.

Three patients were taken off treatment for toxic-ity: one due to stroke, one due to serum sickness and one due to elevated creatinine. One patient was taken off treatment due to lack of improve-ment. Three patients died while on treatment, two due to treatment-related causes, and one due to disease progression. The reason for removal from protocol treatment is under review for one pa-tient.

Ten patients have been evaluated for toxicity. Fa-tal toxicities were reported for two RAEB pa-tients: one due to infection and one due to con-gestive heart failure with arrhythmia and dysp-nea. Grade 4 non-hematologic toxicities were re-ported for two RARS patients: one with cere-brovascular ischemia and one with elevated liver enzymes.


S0020/II



Institutions Total Reg

Oklahoma, Univ of Ozarks Reg CCOP

3 3

Grand Rapids CCOP 2Davis, U of CA 1Puget Sound 1Rochester, Univ of 1Upstate Carolina 1Wayne State Univ 1Wichita CCOP 1Total (9 Institutions) 14


Registrations ending December 31, 2002; Data as of January 29, 2003

ATG +

Cyclosporine ATG +

Cyclosporine NUMBER REGISTERED 14 TOXICITY ASSESSMENT 11 INELIGIBLE 3 Evaluable 9 ELIG./ PEND. ELIG. 11 Too Early 2 Analyzable, Pend. Elig. 3


All eligible and selected ineligible patients included Registrations ending December 31, 2002; Data as of January 29, 2003

ATG + Cyclosporine ATG + Cyclosporine (n=12) (n=12)

AGE RACE Median 62 .2 White 12 100% Minimum 27 .2 Maximum 80 .3 FAB TYPE RA 3 25% SEX RARS 4 33% Males 6 50% RAEB 5 42% Females 6 50% HISPANIC Ye s No

1 8% 11 92%


S0020/II

Treatment Summary

All eligible and selected ineligible patients included Registrations ending December 31, 2002; Data as of January 29, 2003

ATG +

Cyclosporine NUMBER ON PROTOCOL TREATMENT 3 NUMBER OFF PROTOCOL TREATMENT 9 REASON OFF TREATMENT Treatment completed as planned 1 Toxicity or side effects 3 Refusal unrelated to toxicity 0 Progre sion/relapse s Death

0 3

Other - not protocol specified 1 Reason under review 1MAJOR PROTOCOL DEVIATIONS 0


All eligible and selected ineligible patients included Non-Hematologic Toxicities Only

Toxicities with No Entries for Grades 3 to 5 Have Been Suppressed Registrations ending December 31, 2002; Data as of January 29, 2003

ATG + Cyclosporine ATG + Cyclosporine (n=10) (n=10)

Grade

Grade

TOXICITY Unk ≤ 2 3 4 5 TOXICITY Unk ≤ 2 3 4 5 Allergy/h persensitivity yAnorexia

0 9 1 0 0 LVEF decrease/CHF 1 8 0 0 1

1 8 1 0 0 Nausea 1 8 1 0 0Arthralgia 0 9 1 0 0 Pleuritic pain 0 9 1 0 0Bilirubin increase 0 9 0 1 0 Rectal bleeding/hemat cheziao

SGOT (AST) increase 0 9 1 0 0

Cerebrovascular ischemia 0 9 0 1 0 0 9 0 1 0Confusion 0 9 1 0 0 SGPT (ALT) increase 0 9 0 1 0Dyspnea 0 7 2 0 1 Serum sickness 0 8 2 0 0Febrile neutropenia 0 9 1 0 0 Supraventricular arrhy mia th

Ventricul r arrhythmia 0 8 1 0 1

Hyperglycem a iHypertension

0 9 1 0 0 aVomiting

0 9 1 0 0 0 9 1 0 0 0 9 1 0 0

Hyponatrem iaHypotension

0 9 1 0 0 0 9 1 0 0 MAXIMUM GRAD E

ANY ICITY

Infection w/o 3-4 neutropenia 0 9 0 0 1 TOXNumber

0

2

4

2 Infection with 3-4 neutropenia 0 9 1 0 0 2


S0020/II

S0106 Phase III

A Phase III Study of the Addition of Gemtuzumab Ozogamicin (MylotargTM) During Induction Therapy and Post-Consolidation Therapy Versus

Standard Induction and Consolidation Therapy with Daunomycin and Cytosine Arabinoside for Patients Under Age 56 with Previously Untreated

de novo Acute Myeloid Leukemia (AML)

Study Coordinators: S Petersdorf, D Head, M Slovak, C Willman

Statistician: J Jacobson


Schema

RANDOMIZATION

DaunomycinGemtuzumabAra-C

HiDaC3 cycles

No additional therapy

Gemtuzumab for 3 cycles

Induction Consolidation Post-Consolidation

DaunomycinAra-C

HiDaC3 cycles

Objectives To compare overall survival (OS) of patients un-der age 56 with previously untreated, non-M3, AML who receive gemtuzumab ozogamicin ver-sus patients who receive chemotherapy alone.

To compare the complete remission rate achieved by the addition of gemtuzumab ozogamicin to standard induction chemotherapy to that achieved with standard induction chemotherapy in patients under the age of 56 with previously untreated, de novo, non-M-3 AML.

To estimate the frequency and severity of toxici-ties of the gemtuzumab ozogamicin regimen.

To evaluate the prognostic significance of FLT3 mutations prior to therapy, and of minimal resid-ual disease in remission specimens collected be-fore and after consolidation therapy and after

post-consolidation therapy with gemtuzumab ozogamicin.

To evaluate the prognostic significance of the flow cytometric detection of minimal residual disease in specimens collected before and after consolidation therapy and after post-consolidation therapy with gemtuzumab ozogamicin

Patient Population Patients must have a morphologically confirmed diagnosis of acute myeloid leukemia (AML) with FAB classification other than M3, based on bone marrow aspiration and biopsy performed within 14 days prior to registration. Patients with M3 AML or blastic transformation of chronic mye-logenous leukemia are not eligible. Patients with preexisting hematologic disorder evolving to AML such as myelodysplasia or secondary leu-kemia are not eligible.


S0106/III

Patients must not have received systemic chemo-therapy or more than one dose of intrathecal chemotherapy for acute leukemia. Administration of hydroxyurea to control high cell counts prior to registration is permitted.

Patients must have reached their 18th birthday but not reached their 56th birthday and must have a Zubrod performance status in 0-3. Patients must have normal hepatic and left ventricular function. Patients with unstable cardiac arrhythmias or un-stable angina are not eligible.

Stratification/Descriptive Factors For treatment randomization, patients will be stratified by preinduction cytogenetic risk status: favorable vs intermediate vs unfavorable vs inde-terminate.

Accrual Goals The accrual goal for this study is to randomize 640 eligible patients (320 per arm). Two interim analyses will be conducted during the course of this study; they will be done when approximately 33% and 67% of the deaths have occurred.


S0106/III

S0112 Phase II

A Phase II Study of Daunomycin and Ara-C, Both Given by Continuous IV Infusion For Previously Untreated Non-M3 Acute Myeloid Leukemia (AML)

in Patients of Age 56 or Older

Study Coordinators: T Chauncey, A List, D Head, M Slovak, C Willman




Objectives To test whether an induction regimen of dauno-mycin and Ara-C, both given by continuous in-travenous infusion, is sufficiently effective for previously untreated non-M3 AML in patients age 56 or older to warrant investigation in Phase III trials.

To estimate the frequency and severity of toxici-ties of this regimen in this group of patients.

To assess in a preliminary manner the frequency and prognosis of functional and phenotypic P-glycoprotein (Pgp) expression, cytogenetics, and pharmacokinetic characteristics in this popula-tion.

Patient Population Patients must have a morphologically confirmed diagnosis of acute myeloid leukemia (AML) with FAB classification other than M3, based on bone marrow aspiration and biopsy performed within 14 days prior to registration. Patients with M3 AML or blastic transformation of chronic mye-logenous leukemia are not eligible.

Patients must not have received prior systemic chemotherapy for acute leukemia. Administration of hydroxyurea to control high cell counts prior to registration is permitted. A history of prior treat-ment of MDS with low dose cytosine arabinoside is permitted; however, 30 days must have elapsed from prior treatment and all toxicities resolved. If indicated, a single dose of intrathecal chemother-apy may also be given before or concurrent with induction chemotherapy.

Patients must have reached their 56th birthday. Patients must have a Zubrod performance status of 0-3 and must have adequate hepatic, renal, and

cardiac function. Patients with unstable cardiac arrhythmias or unstable angina are not eligible.

Accrual Goals Initially, 30 eligible patients will be accrued. If fewer than nine of these patients achieve CR the study will be closed. Otherwise, 25 additional eligible patients will be accrued for a total of 55 eligible patients.

Summary Statement The study was temporarily closed to accrual on May 15, 2002 after the goal for the first stage of accrual was met. The study was reactivated on July 1, 2002 for the second stage of accrual.

As of December 31, 2002, 50 patients have been accrued to this study. Ten patients are ineligible, including five who did not have AML according to protocol criteria and one with Zubrod perform-ance status 4 at the time of registration. The re-maining ineligible patients are included in the fol-lowing analysis: two without required pretreat-ment tests, one with no documentation of eligibil-ity criteria, and a fourth for whom the required pretreatment cytogenetic specimen was not sub-mitted.

One patient who died before study treatment could be given is coded as not analyzable and is excluded from the analysis. One patient had a major protocol deviation due to receiving DNR by IVPB rather than by continuous infusion as per protocol.

One patient was taken off treatment due to toxic-ity (cerebrovascular ischemia and sepsis), two pa-tients were taken off treatment by the treating physician, two patients discontinued treatment due to progression although not per protocol, and three patients refused protocol-directed second


S0112/II

induction attempts. Reasons for removal from protocol treatment are under review for four pa-tients.

Forty-one patients have been evaluated for toxici-ties of induction therapy. Eleven patients have died: four patients from hemorrhage, three from infection, one from cerebrovascular ischemia, and one from congestive heart failure. The deaths of two patients are currently under review.

Grade 4 non-hematologic toxicities have been re-ported for five other patients: one patient with fa-

tigue and dyspnea, one with edema and catheter-related infection, and one each with dyspnea, anorexia, and increased bilirubin.

Thirteen patients have been evaluated for toxici-ties during consolidation. There have been no fa-tal toxicities. Grade 4 non-hemotologic toxicities have been reported for one patient: CNS hemor-rhage, pneumonia, ARDS, dyspnea, confusion, anxiety and an increase in bilirubin.




Total Reg

Wichita CCOP 16 Akron Gen Med Ctr/Cleveland Clinic OH 1

Columbus CCO PLSU-Shreveport

3 Central IL CCOP 1 3 Davis, U of CA 1

Puget Sound 3 Kansas City CCO PLoyola University

1 St Louis University 3 1 Sutter Hlth Western/Davis, U of CA 3 Oregon Hlth Sci niv U

Providence Hosp 1

Arizona, U of 2 1 Grand Rapids CCOP 2 Upstate Carolina 1 Oakwood Hospital/Michigan, U of 2 Utah, U of 1 Rochester, Univ of 2 Total (20 Institutions) 50 St Louis CCOP 2



DNR/Ara-C DNR/Ara-C NUMBER REGI TERED S INELIGIBLE

50 TOXICITY ASSESSMENT 39

10 Evaluable 37 Insufficient Documentation 3 Too Early 2 Irreversible 2 Reversible 1 ELIG./ PEND. ELIG. 40 Analyzable, Pend. Elig. 8 Not Analyzable 1


All eligible and selected ineligible patients included Registrations ending December 31, 2002; Data as of February 26, 2003

DNR/Ara-C DNR/Ara-C (n=43) (n=43)

AGE HISPANIC Median 68 7 .

56 No 43 100%

Minimum 0 .85

Maximum .2 RACE

98%

White 42 SEX

18 Black 1 2%

Males 42% Females 25 58%


S0112/II

Treatment Summary

All eligible and selected ineligible patients included Registrations ending December 31, 2002; Data as of February 26, 2003

DNR/Ara-C NUMBER ON PROTOCOL TREATMENT 3

NUMBER OFF PROTOCOL TREATMENT 40 REASON OFF TREATMENT Treatment completed as planned 18 Toxicity or side effects 1 Refusal unrelated to toxicity 3 Progr ssion/relapse e Death

0 10

Other - not protocol specified 4 Reason under review 4 MAJOR PROTOCOL DEVIATIONS 1


Induction All eligible and selected ineligible patients included




Grade

Grade

TOXICITY Unk ≤ 2 3 4 5 TOXICITY Unk ≤ 2 3 4 5 Abdominal pain/cramping 0 40 1 0 0

Hypokalemia 0 38 2 1 0

Alkaline phosphatase in rease cAllergy/h persensitivity

0 40 1 0 0 Hyponat emia rHypoxia

0 34 6 1 0y

Anorexia 0 40 1 0 0 1 37 2 1 0 0 33 6 2 0 Infection with 3-4 neutropenia 0 28 12 1 0

Anxiety/agitation 0 40 1 0 0 LVEF decrease/CHF 0 39 1 0 1Apnea 0 40 1 0 0 Local injection site reaction 0 40 1 0 0Bilirubin increase 0 38 2 1 0 Melena/ GI bleeding 0 39 2 0 0CNS hemorrhage 0 38 0 0 3 Muscle weakness (not neuro) 0 40 1 0 0Cardiac ischemia/infarction 0 40 1 0 0 Myalgi a

Nausea 0 40 1 0 0

Catheter related infection 0 39 1 1 0 0 38 3 0 0Cerebrovascular ischemia 0 40 0 0 1 Pleural effusions 0 39 2 0 0Confusion 1 39 1 0 0 Pneumonitis/infiltrates 0 39 1 1 0Constipation/bowel obstruction 0 40 1 0 0 Pruritus 0 40 1 0 0Dehydration 0 40 1 0 0 Pulmonary edema 1 39 1 0 0Diarrhea without colostomy 0 38 3 0 0 Rash/desquamation 1 35 5 0 0Dyspnea 1 33 2 5 0 Reportable adverse event, NOS 0 39 0 0 2Edema 1 39 0 1 0 Respiratory infect w/ neutrop 1 33 6 0 1Epistaxis 0 39 2 0 0 SGOT (AST) increase 0 40 1 0 0Esophagitis/dysphagia 0 39 2 0 0 Sinus tachycardia 0 38 3 0 0External auditory canal-otitis 0 39 1 1 0 Somnolence/consciousness loss 0 40 1 0 0Fatigue/malaise/leth argyFebrile neutropenia

1 33 5 2 0 Stomatitis/pharyngitis 0 37 4 0 0 0 24 16 0 1 Supraventricular arrhythmia 1 39 1 0 0

Hematuria 1 39 1 0 0 Thrombosis/embolism 0 40 1 0 0Hemoptysis 1 38 2 0 0 Urinary tr infect w/ neutrop 0 38 2 0 1Hemorrhage w/ 3-4 thrombocyt 0 35 4 0 2 Weakness (motor neuropathy) 0 39 2 0 0Hyperglycemia 0 40 1 0 0 Hypernatremia 0 40 1 0 0 MAXIMUM GRAD E

ANY TOXICITY

Hypoalbuminemia 0 40 1 0 0 Hypocalcemia 0 39 1 1 0 Number 0 4 21 5 11


S0112/II


Consolidation All eligible and selected ineligible patients included




Grade

Grade

TOXICITY Unk ≤ 2 3 4 5 TOXICITY Unk ≤ 2 3 4 5 ARDS 0 12 0 1 0

Hypoxia 0 12 1 0 0

Alkalosis 0 12 1 0 0 Infection w/o 3-4 neutropenia 0 12 1 0 0Anxiety/agitation 0 12 0 1 0 Infection with 3-4 neutropenia 0 12 1 0 0Bilirubin increase 0 12 0 1 0 Infection, unk ANC 0 12 1 0 0CNS hemorrhage 0 12 0 1 0 Melena/ GI bleeding 0 12 1 0 0Catheter related infection 1 11 1 0 0 Myalgia 1 11 1 0 0Confusion 0 12 0 1 0 Petechiae/purpura 0 12 1 0 0Diarrhea without colostomy 0 12 1 0 0 Rash/desquamation 0 12 1 0 0Dyspnea 0 12 0 1 0 Respiratory infect w/ neutrop 0 12 0 1 0Epistaxis 0 12 1 0 0 Urinary tr infect w/ neutrop 0 12 1 0 0Febrile neutropenia 0 11 2 0 0 Weakness (motor neuropathy) 0 12 1 0 0Hemoptysis 0 12 1 0 0 Hemorrhage w/ 3-4 thrombocyt 0 12 1 0 0 MAXIMUM GRADE Hypercalcemia 0 12 1 0 0 ANY ICITY TOX

Number

0

4

8

1 Hyperglycemia 0 11 2 0 0 0Hyponatremia 0 12 1 0 0


S0112/II

S0117 Phase II

A Phase II Study of Gemtuzumab Ozogamicin (MylotargTM) and Standard Dose Ara-C for Patients with Relapsed Acute Myeloid Leukemia (AML).

Study Coordinators: J Godwin, M O'Donnell, D Head, M Slovak, C Willman

Statistician: J McCoy


Objectives To test whether an induction regimen of standard dose Ara-C combined with gemtuzumab ozogamicin (MylotargTM) is sufficiently safe and effective therapy for patients with relapsed acute myeloid leukemia (AML) to warrant further in-vestigation in Phase III trials.


To assess in a preliminary manner the prognostic significance of drug resistance phenotype, cyto-genetics, and molecular genetic characteristics in this group of patients.

Patient Population Patients must have a morphologically confirmed diagnosis of acute myeloid leukemia (AML) with FAB classification other than M3, based on bone marrow aspiration and biopsy performed within 14 days prior to registration. Patients with M3 AML or blastic transformation of chronic mye-logenous leukemia are not eligible. Patients with prior MDS or secondary AML are eligible. Pa-tients must be in relapse from documented CR.

Patients must not have received prior MylotargTM for acute leukemia. Patients relapsing following autologous or allogeneic hematopoietic stem-cell transplant are not eligible for this trial. Admini-stration of hydroxyurea to control high cell counts prior to registration is permitted. Prior treatment with other investigational agents is permitted; however, four weeks must have elapsed from prior treatment and all toxicities re-solved.

Patients must have CD33 positive AML, be at least 18 years of age, and have a Zubrod perform-ance status of 0, 1, or 2. Patients must have ade-quate hepatic function, must not have clinical or documented CNS involvement with AML, and must have a WBC ≤ 30,000. Patients with unsta-ble cardiac arrhythmias or unstable angina are not eligible.

Accrual Goals Initially, 30 eligible patients will be accrued. If fewer than nine of these patients achieve CR, the study will be closed. Otherwise, 25 additional eligible patients will be accrued for a total of 55 eligible patients.


S0117/II

S0125 Phase II

A Phase II Study of Chimerism-Mediated Immunotherapy (CMI) Using Nonmyeloablative Allogeneic Peripheral Blood Stem Cell Transplantation in

Older Patients with Acute Myeloid Leukemia (AML) in First Complete Remission (A BMT Study).

Study Coordinators: P McSweeney, T Chauncey, S Bearman, A Mohamed, C Willman

Statisticians: K Kopecky, H Gundacker


Objectives To test whether nonmyeloablative allografting us-ing conditioning with pre-transplant fludarabine and total body irradiation and post-transplant cyc-losporine/mycophenolate mofetil in older patients with AML in first complete remission is suffi-ciently effective in terms of survival one year af-ter transplant to warrant Phase III investigation.


To perform chimerism studies on blood and mar-row cell populations after transplant in order to investigate whether chimerism patterns in bone marrow and blood are associated with relapse and/or GVHD.

To investigate in a preliminary manner the asso-ciation of cytogenetics, immunophenotypic, and molecular biologic features detected in pre- and post-transplant specimens with transplant out-comes and risk of relapse.

Patient Population Patients must have a morphologically confirmed diagnosis of AML or secondary AML with FAB classification other than M3. Patients with M3 AML or blastic transformation of chronic mye-logenous leukemia are not eligible. Patients must have received remission induction chemotherapy and must have A1 marrow, B1 blood, and C1 ex-

tramedullary disease status. At least one cycle of consolidation therapy is recommended although not required, and additional cycles of consolida-tion therapy are permitted. Patients must be within 180 days of their initial diagnosis of AML. Patients must have a genotypically HLA-identical sibling who is medically fit and has signed an in-formed consent to be a donor.

Patients who have received any organ transplant for which they remain on immunosuppressive treatment or any allogeneic hematopoietic stem cell transplant are not eligible.

Patients must be at least 55 years old but not past their 70th birthday. Patients must have a Zubrod performance status of 0, 1, or 2, and must have a negative HIV test within 28 days prior to registra-tion. Patients with a history of CNS leukemia must have a lumbar puncture demonstrating the absence of leukemia cells within 7 days before registration.

Accrual Goals Initially, accrual will continue until 25 eligible patients receive protocol transplant. If 16 or fewer of these patients survive at least six months after transplant, the study will be closed. Otherwise, accrual will continue until an additional 26 eligi-ble patients receive protocol transplant, for total of 51 eligible transplanted patients.


S0125/II

C9710 Phase III Intergroup Coordinating Group: CALGB

Phase III Randomized Study of Concurrent Tretinoin and Chemotherapy with or without Arsenic Trioxide (As2O3) (NSC #706363) as Initial

Consolidation Therapy Followed by Maintenance Therapy with Intermittent Tretinoin Versus Intermittent Tretinoin Plus Mercaptopurine and

Methotrexate for Patients with Untreated Acute Promyelocytic Leukemia

Intergroup Participants: CALGB, SWOG, COG, ECOG, NCIC

Study Coordinators: B Powell (CALGB), S Coutre, M Tallman (ECOG), S Couban (NCIC), J Feusner (COG)




Schema

RANDOMIZE

CR or PR*ATRA + Ara-C+ DNR

As 2O3

ATRA + 6-MP/MTX for 1 Year

RANDOMIZE ATRA for 1 Year

ATRA + DNR

INDUCTION

ATRA + Ara-C+ DNR

CONSOLIDATIONTHERAPY

CR

MAINTENANCE THERAPY

*Patients who fail to achieve CR or PR after Induction Therapy are removed from protocol treatment.

Objectives To compare the efficacy (event-free survival) and toxicities of two induction/consolidation therapies for patients with untreated APL: ATRA/Ara-C/daunorubicin with or without arsenic trioxide (As2O3).

To evaluate the efficacy (disease-free survival) and toxicities of maintenance therapy with inter-mittent ATRA vs intermittent ATRA plus 6-

MP/MTX for patients with APL who achieve a complete response.

To explore the relationship between CD56 ex-pression at diagnosis and clinical outcomes.

To evaluate the cardiac toxicity of intensive daunorubicin therapy, as given in this study, to pediatric patients.


C9710/III

Patient Population Patients must have a clinical diagnosis of acute promyelocytic leukemia (APL) with proof of APL morphology (FAB-M3) confirmed by RT-PCR assay. A patient may be entered prior to completion of RT-PCR studies, but a patient who is subsequently found to be PML-RARα negative and RARα-PML negative will be removed from protocol treatment.

Patients must not have received any systemic de-finitive treatment for APL, including cytotoxic chemotherapy or retinoids. Prior therapy with corticosteroids, hydroxyurea or leukapheresis is allowed.

Accrual Goals The accrual goal for this study is 420 patients.

Summary Statement This study opened to accrual in CALGB on June 15, 1999, and in SWOG on July 15, 1999. On May 1, 2001, the protocol was amended (Update #5) to change the randomization for the mainte-nance phase of therapy. There is no longer an "Observation" arm. The new randomization is be-tween ATRA and ATRA + Chemotherapy. Effec-tive July 15, 2001, institutions without IRB ap-proval of Update #5 were not able to register pa-tients to the protocol.

As of December 31, 2002, a total of 270 patients have registered to this study, including 63 from SWOG institutions.

Based on the CALGB report of November 2002, a total of 141 patients have been evaluated for in-duction toxicity, including 116 registered from adult institutions (CALGB, ECOG, SWOG). Three patients have died: one with hemorrhage, one with arrhythmia, and one with renal failure. Toxicities of Grade 4 were reported for 62 of the 141 patients including 49 from adult institutions. For patients from adult institutions the Grade 4 non-hematologic toxicities included three reports each of infection, pneumonitis and hyperglyce-mia, two reports each of ARDS, DIC, anorexia, hepatic toxicity, and unspecified pulmonary tox-icity and one report each of stomati-tis/pharyngitis, vomiting, hypokalemia, myositis, myalgia, confusion, elevated CPK, and an un-specified syndrome. For patients from pediatric institutions Grade 4 non-hematologic toxicities included three reports of infection, two reports of febrile neutropenia, and one report each of ven-tricular arrhythmia, anorexia, stomati-tis/pharyngitis, vomiting, decreased fibrinogen, acidosis, and an unspecified pulmonary toxicity.

The complete November 2002 summary of this study from CALGB is available on the Southwest Oncology Group web site.




Total Reg

Columbus CCOP 8 Columbia River CCO P

Gulf Coast MBCCOP 1

Loyola University 6 1 Atlanta Reg CCOP 4 LSU-Shrevepo rt

Michigan, U of 1

Stanford University/City of Hope Med Ctr 4 1 Cleveland Clinic OH 3 Oakwood Hospital/Michigan, U of 1 Montana CCOP 3 Providence Hosp 1 New Mexico COP MBCPuget Sound

3 Rochester, Univ of 1 3 San Antonio, U of TX 1

Wichita CCOP 3 Scott & White CCOP 1 Central IL CCOP 2 Thompson Ca Surv Ctr/San Antonio, U of TX 1 Davis, U of CA 2 Tulane University 1 Grand Rapids CCOP 2 Utah, U of 1 Mississippi, Univ of 2 Wayne State Univ 1 Sutter Hlth West rn/Davis, U of CA e 2 Wenatchee Valley/Puget Sound 1 Upstate Carolina 2 Total (29 Institutions) 63


C9710/III

E2997 Phase III Intergroup Coordinating Group: ECOG

Phase III Randomized Trial of Fludarabine and Cyclophosphamide versus Fludarabine for Previously Untreated Chronic Lymphocytic Leukemia

Intergroup Participants: ECOG, SWOG, CALGB

Study Coordinators: I Flinn (ECOG), M Hussein, M Grever (CALGB)




Schema

RANDOMIZE

Arm A:Cyclophosphamide + Fludarabine (20 mg/m2)*

Arm B:Fludarabine (25 mg/m2)*

* Repeat every 28 days for a maximum of 6 cycles

Objectives To evaluate the complete response rate of fluda-rabine and cyclophosphamide versus fludarabine alone in patients with previously untreated B cell chronic lymphocytic leukemia (CLL).

To evaluate the toxicity of fludarabine and cyclo-phosphamide versus fludarabine alone in patients with previously untreated CLL.

To evaluate the overall survival of patients with previously untreated CLL treated with fludara-bine and cyclophosphamide versus fludarabine alone.

To determine whether the expression of proteins that have been specifically implicated in the regu-lation of DNA-damage induced apoptosis of lym-phoid cells (i.e. p53; mdm2; GST; Bcl-2; Mcl-1; Bax; p27; and caspase-3) correlate with response

to chemotherapy in previously untreated patients with chronic lymphocytic leukemia.

The differential expression of genes in the CLL leukemic cells either at initiation of therapy or following relapse and progression of disease will be examined by cDNA microarray technology to determine whether there is a relationship with clinical response or resistance. Point mutations in immunoglobulin heavy chain variable region genes will be examined by DNA sequencing at initiation of therapy and following either relapse or progression of disease to determine whether these mutations correlate with clinical response, resistance to treatment, or other parameters.

Custom-designed oligonucleotide microarray technology will be used to screen for mutations in the Ataxia Telangiectasia Mutated (ATM) gene in Chronic Lymphocytic Leukemia to determine if


E2997/III

there are differences in mutations between normal and CLL patients, and if so, what the relationship of ATM mutations is to clinical response, resis-tance to treatment, or other parameters.

Patient Population Patients must have a diagnosis of CLL (as de-fined by the NCI criteria) of any stage. Patients must require chemotherapy.

Patients may not have had prior cytotoxic chemo-therapy. Patients with a history of steroid treat-ment for CLL, autoimmune hemolytic anemia, or autoimmune thrombocytopenia are not eligible.

Patients must have adequate renal and hepatic function. Patients must have reached their 18th birthday and have an ECOG performance status of 0, 1, or 2. Patients with active infections are not eligible.

Stratification/Descriptive Factors Patients are stratified by stage: stages 0, 1, and 2 vs stages 3 and 4.

Accrual Goals The accrual goal for this study is 252 eligible pa-tients.

Summary Statement This study opened to accrual in ECOG on De-cember 23, 1999 and in SWOG on October 15, 2002. As of December 31, 2002, 158 patients have registered to this study, including one pa-tient from a SWOG institution (Sinai Hospi-tal/San Antonio, University of Texas).

Based on the ECOG report of November 2002, toxicity information has been reported for 49 pa-tients. Grade 4 non-hematologic toxicities for the patients receiving the combination of fludarabine and cyclophosphamide include one report each of fatigue, rash/desquamation, infection with neu-tropenia, hypercalcemia, hyperglycemia, hypo-calcemia and elevated creatinine. One grade 4 non-hematologic toxicity (elevated bilirubin) has been reported for a patient on fludarabine alone.

The complete November 2002 summary of this study from ECOG is available on the Southwest Oncology Group web site.


E2997/III

Documents

Leukemia Committee Agenda 2003/Leukemia.pdf · Dr. Schiffer Proposed Studies S0106 A Phase III Study of the Addition of Gemtuzumab Ozogamicin (Mylotarg™) During Induction Therapy