13-TLEC Natural History and Biology of Long-Term Late

CONFIDENTIAL

13-TLEC Natural History and Biology of Long-Term Late Effects

Following Hematopoietic Cell Transplant for Childhood Hematologic Malignancies

Case Report Form Example

13-TLEC Case Report Forms

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Contents Form and Visit Matrix.............................................................................................................................................................. 3

Demographics Form ................................................................................................................................................................ 4

Form notes .......................................................................................................................................................................... 4

Inclusion/Exclusion Form (Screening folder) .......................................................................................................................... 5

Form notes .......................................................................................................................................................................... 6

Help text .............................................................................................................................................................................. 6

Medical History form (Baseline Visit) ...................................................................................................................................... 7

Form notes .......................................................................................................................................................................... 8

Disease status dynamic search list ...................................................................................................................................... 9

Help text .............................................................................................................................................................................. 9

Exam (Baseline, Day 30, Day 100, Day 180, 1 year, and 2 year visits) .................................................................................. 10

Ranges ............................................................................................................................................................................... 10

Karnofsky/Lansky dynamic search list .............................................................................................................................. 11

Medications (Baseline, Day 100, Day 180, 1 year, and 2 year visits) .................................................................................... 12

Form notes ........................................................................................................................................................................ 12

Help text ............................................................................................................................................................................ 12

Corticosteroid ....................................................................................................................................................................... 13

Log line expanded ............................................................................................................................................................. 13

Help text ............................................................................................................................................................................ 14

Form level help text ...................................................................................................................................................... 14

Question level help texts .............................................................................................................................................. 14

Labs (Baseline, Day 30, Day 100, Day 180, 1 year, and 2 year visits).................................................................................... 15

Form notes ........................................................................................................................................................................ 16

Help text ............................................................................................................................................................................ 16

Ranges ............................................................................................................................................................................... 16

Unit dictionary .................................................................................................................................................................. 17

DXA scan (Baseline, 1 year, and 2 year visits) ....................................................................................................................... 18

Form notes ........................................................................................................................................................................ 18

Radiograph ............................................................................................................................................................................ 18

Form notes ........................................................................................................................................................................ 18

Conditioning Regimen (Conditioning visit) ........................................................................................................................... 19

Log Line expanded ............................................................................................................................................................ 20

Form notes ........................................................................................................................................................................ 20

Conditioning agent dynamic search list ............................................................................................................................ 20

Transplant Form (Transplant visit) ........................................................................................................................................ 22


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Form notes ........................................................................................................................................................................ 22

Post Transplant Follow up (Day 30, Day 100, Day 180, 1 year, and 2 year visits) ................................................................ 23

Form notes ........................................................................................................................................................................ 24

Medical Conditions (Day 100, Day 180, 1 year and 2 year visits) ......................................................................................... 25

Help text ............................................................................................................................................................................ 25

Treatments ............................................................................................................................................................................ 27

Acute GVHD (Day 100, Day 180, 1 year and 2 year visits) .................................................................................................... 28

Form notes ........................................................................................................................................................................ 29

Therapy dropdown choices: .......................................................................................................................................... 29

Chronic GVHD ....................................................................................................................................................................... 30

Form notes ........................................................................................................................................................................ 31

Therapy dropdown choices: .......................................................................................................................................... 31

Unanticipated Problem ......................................................................................................................................................... 32

Form notes ........................................................................................................................................................................ 32

Study Exit .............................................................................................................................................................................. 33

Form notes ........................................................................................................................................................................ 33

Help text ............................................................................................................................................................................ 33


3

Form and Visit Matrix

Subject Screening Baseline Conditioning Transplant

Day 30

Day 100

Day 180 Year 1 Year 2

Steroid Review

Study Exit UAP

Demographics

Inclusion/Exclusion criteria

Medical history

Post transplant follow up

Exam

Medical conditions

Treatments

Medications

Corticosteroid

Labs

DXA scan

Radiograph

Acute GVHD

Chronic GHVD

Conditioning regimen

Transplant

Unanticipated Problem

Study Exit

Yellow highlight indicates forms that are dynamically added within a visit when a trigger question is answered ‘Yes’.


4

Demographics Form

Form notes This is the primary form for 13-TLEC. The Age field is derived from the Date of birth and Date informed

consent signed. If the Age is > 21, the form will be marked non-compliant and the subject does move on in the

study. The Subject ID and Subject status fields are derived and not able to be edited. The Subject status after

completion of the Demographics form is ‘Screening’.


5

Inclusion/Exclusion Form (Screening folder)


6

Form notes If all Inclusion questions are answered Yes and all Exclusion questions are answered No then the Eligibility

question is derived to be Yes. The Enrollment date field will be derived as the date the Eligibility question is

Yes. The Screen failure date will be derived as the date the Eligibility question is No. The subject status at the

completion of this form will be ‘Enrolled’ if eligibility is Yes and ‘Screen failed’ if eligibility is No.

Help text

Questions marked with a have associated help text.

Help text for diseases allowed:

Help text for conditioning regimen:


7

Medical History form (Baseline Visit)


8

Form notes The indented questions are visible once the form is saved if the question preceding it is selected to be Yes.


9

Disease status dynamic search list The disease status question is a dynamic search listed based on the disease selected. See table below for a list of

values.

Acute lymphoblastic leukemia (ALL) 1st complete remission

2nd complete remission

≥ 3rd complete remission

Acute myelogenous leukemia (AML or ANLL) 1st complete remission

2nd complete remission

≥ 3rd complete remission

Chronic myelogenous leukemia (CML) Complete hematologic remission

First chronic phase

Second or greater chronic phase

Accelerated phase

Blast crisis

Juvenile myelomonocytic leukemia (JMML/JCML) Complete remission

Hematologic improvement

No response/stable disease

Progression from hematologic improvement

Relapse from complete remission

Not assessed

Myelodysplastic (MDS) / myeloproliferative (MPN)

diseases Complete remission

Hematologic improvement

No response/stable disease

Progression from hematologic improvement

Relapse from complete remission

Not assessed

Help text Dyslipidemia

Fasting levels:

Triglyceride level >150 mg/dL;

HDL cholesterol level <40 mg/dL;

and/or LDL cholesterol level >130 mg/dL

Osteopenia

Osteopenia: Z-score between -1.0 and -2.0 in any area assessed by DXA or increased radiolucency reported by

an attending radiologist on radiograph, computed tomography, or magnetic resonance imaging.

Osteoporosis

Osteoporosis: Z-score less than -2.0 in any area assessed by DXA and/or non-traumatic fracture.


10

Exam (Baseline, Day 30, Day 100, Day 180, 1 year, and 2 year visits)

Form notes

The DXA scan question is visible for the Baseline, 1 year and 2 year visits. Based on the answer the DXA

and/or Radiograph form will appear in the visit folder. The values for Karnofsky and Lansky will appear based

on the value in the scale question. On the Baseline visit an edit check will fire if the value is <60 (exclusion

criterion).

Ranges

Field Units (standard unit) Range – listed in the help text

Height in

cm (standard)

63 – 213 cm

25-83 in

Weight lbs

kg (standard)

1 – 250 kg

3 - 551 lbs

Waist circumference in

cm (standard)

20 – 200 cm

7 – 79 in

Systolic blood pressure Fixed unit: mm Hg 50 - 200

Diastolic blood pressure Fixed unit: mm Hg 20 - 125


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Karnofsky/Lansky dynamic search list

UserDataString CodedData

Karnofsky <K> 100 Normal; no complaints; no evidence of

disease 100K

90 Able to carry on normal activity 90K

80 Normal activity with effort 80K

70 Cares for self; unable to carry on normal

activity or to do active work 70K

60 Requires occasional assistance but is able

to care for most needs 60K

50 Requires considerable assistance and

frequent medical care 50K

40 Disabled; requires special care and

assistance 40K

30 Severely disabled; hospitalization

indicated, although death not imminent 30K

20 Very sick; hospitalization necessary 20K

10 Moribund; fatal process progressing

rapidly 10K

Lansky <L> 100 Fully active 100L

90 Minor restriction in physically strenuous

play 90L

80 Restricted in strenuous play, tires more

easily, otherwise active 80L

70 Both greater restrictions of, and less time

spent in, active play 70L

60 Ambulatory up to 50% of time, limited

active play with assistance / supervision 60L

50 Considerable assistance required for any

active play; fully able to engage in quiet play 50L

40 Able to initiate quiet activities 40L

30 Needs considerable assistance for quiet

activity 30L

20 Limited to very passive activity initiated by

others (e.g., TV) 20L

10 Completely disabled, not even passive play 10L


12

Medications (Baseline, Day 100, Day 180, 1 year, and 2 year visits)

Form notes This form is available in Baseline and follow up visit folders. The categories are defaulted to show with the

expectation that ‘Taking?’ will be answered for each. The rest of each line is dependent on this question.

Help text Help text present in the header: “Medications entered should be prescribed, ongoing medications. Do not

include medications given only as needed for a symptom/issue.”


13

Corticosteroid

Log line expanded


14

Help text

Form level help text

Question level help texts


15

Labs (Baseline, Day 30, Day 100, Day 180, 1 year, and 2 year visits)


16

Form notes The form is present for the Baseline and follow up visits but the questions asked vary depending on visit.

Help text Each value that includes a range has help text that lists the expected ranges. In addition, the last 5 lab values

have the following help text.

Ranges

Field Units (standard unit) Format Range Visits Urine protein: mg/dL NNNNN.N 0 – 20,000 All (Baseline, Day 30, Day

100, Day 180, 1 year and 2

year)

Urine albumin: mg/dL(standard)

mg/L NNN.N 0 – 500 All


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Field Units (standard unit) Format Range Visits

Urine microalbumin: mg/dL(standard)

mg/L NNN.N 0 – 500 All

Measured GFR or creatinine clearance:

mL/min/1.73 m2 NNN (no

decimals)

0 – 200 Baseline, 1 year, 2 year

Serum creatinine: mg/dL NN.NN 0.3 – 10 All Urine creatinine: mg/dL NNN.NN 0 – 600 All Cystatin C: mg/L N.NN 0.2 – 3.0 All BUN: mg/dL NN.NN 1 – 30 All 25-OH Vitamin D: nmol/L (standard)

ng/mL

NNN.N 0 – 999 Baseline, Day 100, 1 year

and 2 year

Parathyroid hormone: pg/mL (standard)

pmol/L

NNN.N 0 – 999 Baseline, Day 100, 1 year

and 2 year

Calcium: mg/dL NN.N 5 – 20 Baseline, Day 100, 1 year

and 2 year Serum osteocalcin: μg/L (equivalent

to ng/mL) –

standard

nmol/liter

NNN.NN 0.5 – 100 All but Day 180

Urine N-telopeptide: nmol bone collagen equivalents/mmol creatinine

NNNN 5 – 3000 All but Day 180

Bone specific alkaline phosphatase:

µg/L NNN.N 10 – 99 All but Day 180

Triglycerides mg/dL NNN 0 – 999 All but Day 180

HDL

mg/dL

mmol/L (standard)

NNN.N 0.3 – 5

mmol/L

All but Day 180

LDL mg/dL

mmol/L (standard)

NNN.N 0.3 – 5

mmol/L

All but Day 180

Insulin pmol/L

mcIU/ml

(standard)

NNN.N 0 – 50

mcIU/ml

All but Day 180

Blood glucose mg/dL NNN 30 – 999 All but Day 180

Unit dictionary Questions CodedUnit UnitString Standard Formula

Height and waist circumference

CM cm X

IN in value / 2.54

Weight KG kg X

LBS lbs value * 2.2046

HDL and LDL MG_DL mg/dL

MMOL_L mmol/L X value / 0.0259

Vitamin D NMOL_L nmol/L X

NG_ML ng/mL value / 2.496

Parathyroid PG_ML pg/mL value * 0.105

PMOL_L pmol/L X

Osteocalcin MICROGRAM_L

μg/L (equivalent to ng/mL) X

NMOL_L nmol/liter value * 0.171

Insulin pmol pmol/L value / 0.143988


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mcIU mcIU/ml

Urine albumin and Urine microalbumin

mgdl mg/dL X

mgl mg/L value * 10

DXA scan (Baseline, 1 year, and 2 year visits)

Form notes This form is available at the Baseline, 1 year, and 2 year visits if the trigger question on the Exam form is Yes.

Radiograph

Form notes This form is available at the Baseline, 1 year, and 2 year visits if the trigger question on the Exam form is Yes.


19

Conditioning Regimen (Conditioning visit)


20

Log Line expanded

Form notes The GVHD prevention questions are checkboxes where multiple values can be selected. The choices are based

on the protocol values. The three indented questions for radiation will be available when the form is saved if

Radiation therapy is Yes.

Conditioning agent dynamic search list The agents available to select for Conditioning Regimen are listed in the table.

Agent Agent specify Other, specify

ALG, ALS, ATG, ATS

Anthracycline

Daunorubicin

Doxorubicin (Adriamycin)

Idarubicin

Other anthracycline Text field required

Bleomycin (BLM, Blenoxane)

Busulfan (Myleran)

Carboplatin

Cisplatin (Platinol, CDDP)

Cladribine (2-CdA, Leustatin)

Corticosteroids Methylprednisone (Solu-Medrol)

Prednisone

Dexamethasone

Other corticosteroid Text field required

Cyclophosphamide (Cytoxan)

Cytarabine (Ara-C)

Etoposide (VP-16, VePesid)


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Agent Agent specify Other, specify

Fludarabine

Ifosfamide

Intrathecal therapy

(chemotherapy)

Intrathecal cytarabine (IT Ara-C)

Intrathecal methotrexate (IT MTX)

Intrathecal thiotepa

Other intrathecal drug Text field required

Melphalan (L-Pam)

Mitoxantrone (Novantrone)

Radio labeled Mab Tositumomab (Bexxar) *

Ibritumomab tiuxetan (Zevalin) *

Other radio labeled mAb Text field required

Monoclonal antibody Alemtuzumab (Campath)

Rituximab (Rituxan, anti CD20)

Gemtuzumab (Mylotarg, anti

CD33)

Other Mab Text field required

Nitrosourea Carmustine (BCNU)

CCNU (Lomustine)

Other nitrosourea Text field required

Paclitaxel (Taxol, Xyotax)

Teniposide (VM26)

Thiotepa

Treosulfan

Tyrosine kinase inhibitors

Other drug Text field required


22

Transplant Form (Transplant visit)

Form notes The Match Type questions are based on the Product type selected and appear once the form is saved.


23

Post Transplant Follow up (Day 30, Day 100, Day 180, 1 year, and 2 year visits)


24

Form notes Indented questions are visible based on the answer to the previous question and available when the form is

saved. If either GVHD question is answered Yes the corresponding GVHD form will appear within the visit

folder.


25

Medical Conditions (Day 100, Day 180, 1 year and 2 year visits)

Help text


26


27

Treatments


28

Acute GVHD (Day 100, Day 180, 1 year and 2 year visits)


29

Form notes This form is made available based on a trigger question on the Post Transplant Follow Up form.

Therapy dropdown choices:

ALS, ALG, ATS, ATG

Corticosteroids (systemic)

Corticosteroids (topical)

Cyclosporine (CSA) (Sandimmune, Neoral) ECP (extra-corporeal photopheresis)

FK 506 (Tacrolimus, Prograf)

In vivo monoclonal antibody

Anti CD 25 (Zenapax, Daclizumab, AntiTAC)

Campath

Etanercept (Enbrel)

Infliximab (Remicade)

Other in vivo monoclonal antibody

In vivo immunotoxin Methotrexate (MATX) (Amethopterin)

Mycophenolate mofetil (MMF) (CellCept)

Sirolimus (Rapamycin, Rapamune)

Ursodiol

Blinded randomized trial

Other agent


30

Chronic GVHD


31

Form notes This form is made available based on a trigger question on the Post Transplant Follow Up form.

Therapy dropdown choices:

ALS, ALG, ATS, ATG

Azathioprine

Corticosteroids (systemic)

Corticosteroids (topical) Cyclosporine (CSA) (Sandimmune, Neoral)

ECP (extracorporeal photopheresis)

Hydroxychloroquine (Plaquenil)

Etretinate

FK 506 (Tacrolimus, Prograf)

In vivo monoclonal antibody Anti CD 25 (Zenapax, Daclizumab, AntiTAC)

Campath

Etanercept (Enbrel)

Infliximab (Remicade)

Other in vivo monoclonal antibody

Lamprene (Clofazimine) Mycophenolate mofetil (MMF) (CellCept)

Pentostatin

PUVA (Psoralen and UVA)

Sirolimus (Rapamycin, Rapamune)

Thalidomide

Ursodiol

Blinded randomized trial


32

Other agent

Unanticipated Problem

Form notes This is an unscheduled form available from the subject home page as needed.


33

Study Exit

Form notes This is an unscheduled form available from the subject home page as needed.

Help text

Documents

13-TLEC Natural History and Biology of Long-Term Late