NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry...
Transcript of NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry...
![Page 1: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/1.jpg)
1
NOPHO-DBH AML 2012 Protocol
Research study for treatment of children and adolescents with acute myeloid leukaemia
Initiation presentation based on protocol version 2.1 dd 17/01/2013
Teleconference Study Initiation Belgium 20th of May 2014
![Page 2: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/2.jpg)
2
Sponsor: Vastra Gotaland Regionen Regionens Hus 462 80 Vanersborg Sweden
International Study Coordinators: Jonas Abrahamsson
Belgian National Coordinator:
Principal Investigator: Prof. Dr. Barbara De Moerloose Study coordinators: Maaike Van Hoecke and Rein Demuynck Contact: Tel: 0032 9 332 35 47 Fax: 0032 9 332 49 86
![Page 3: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/3.jpg)
3
![Page 4: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/4.jpg)
4
Checklist at diagnosis
![Page 5: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/5.jpg)
5
AML2012 Overview
MEC
DxEC
R1 BM d22* R2
ADxE
FLADx
HAM HA3E FLA BM**
SCT for HR
CR
No CR
Salvage therapy
MEC
DxEC
R1 BM d22* R2
ADxE
FLADx
HAM HA3E FLA BM**
SCT for HR
CR
No CR
Salvage therapy
HA3E FLA Inv(16) and SR
![Page 6: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/6.jpg)
6
Objectives & endpoints of 1st study
![Page 7: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/7.jpg)
7
1st induction standard arm: MEC
Children < 1y or < 10kg Cytarabine 6.7 mg/kg Etoposide 5 mg/kg Mitoxantrone 0.17 mg/kg
Mtx it*
Cytarabine 200 mg/m2 12h ci iv
Etoposide 150 mg/m2 iv
Mitoxantrone 5 mg/m2 iv
Day 6-12
Day 6-10 Inf 1 hour
Day 1-5 Inf 2 hours
Day 1 2 3 4 5 6 7 8 9 10 11 12
MEC
Mtx it age-adjusted <1y 6 mg 1-<2y 8 mg 2-<3y 10 mg ≥ 3y 12 mg
![Page 8: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/8.jpg)
8
1st induction experimental arm: DxEC
Children < 1y or < 10kg Cytarabine 6.7 mg/kg Etoposide 5 mg/kg Daunoxome 2 mg/kg
Mtx it*
Cytarabine 200 mg/m2 12h ci iv
Etoposide 150 mg/m2 iv
Daunoxome 60 mg/m2 iv
Day 6-12
Day 6, 8 and 10 Inf 1 hours
Day 1-5 Inf 2 hours
Day 1 2 3 4 5 6 7 8 9 10 11 12
DxEC
Mtx it age-adjusted <1y 6 mg 1-<2y 8 mg 2-<3y 10 mg ≥ 3y 12 mg
![Page 9: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/9.jpg)
9
Objectives & endpoints of 2nd study
![Page 10: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/10.jpg)
10
2nd induction standard arm: ADxE
Children < 1y or < 10kg Cytarabine 3.3 mg/kg Etoposide 5 mg/kg Daunoxome 2 mg/kg
Mtx it
Cytarabine 100 mg/m2 iv
Etoposide 150 mg/m2 iv
Daunoxome 60 mg/m2 iv
Day 3-8, 30 min inf, every 12h
Day 2,4,6 1 hour inf
Day 6,7,8 2 hour
Day 1 2 3 4 5 6 7 8
Cytarabine 100 mg/m2 ci Day 1,2
ADxE
Mtx it age-adjusted <1y 6 mg 1-<2y 8 mg 2-<3y 10 mg ≥ 3y 12 mg
![Page 11: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/11.jpg)
11
2nd induction experimental arm: FLADx
Children < 1y or < 10kg Cytarabine 67 mg/kg Fludarabine 1 mg/kg Daunoxome 2 mg/kg
Fludarabine 30 mg/m2 iv (30min)
Cytarabine 2000 mg/m2 inf (3h)
Daunoxome 60 mg/m2 iv inf (1h)
Day
Day 1-5
Day 1-5 4h after fludarabine
Day 2,4,6 immediately after fludarabine
Mtx it
1 5 6 4 3 2
FLADx
Mtx it age-adjusted <1y 6 mg 1-<2y 8 mg 2-<3y 10 mg ≥ 3y 12 mg
![Page 12: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/12.jpg)
12
Overview of consolidation
HAM HA3E FLA
SCT HAM
Standard risk
High risk
No donor
HA3E FLA Inv(16)
Note that SR patients with Inv(16) only receive two consolidation
blocks
![Page 13: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/13.jpg)
13
HAM
Children < 1y or < 10 kg Cytarabine 33 mg/kg Mitoxantrone 0.33 mg/kg
Cytarabine 1000 mg/m2 inf (2h)
Mitoxantrone 10 mg/m2 iv inf (1 hour) Day 1-3 every 12 hours
Day 3,4,5
Mtx it
Day 1 5 4 3 2
HAM
Mtx it age-adjusted <1y 6 mg 1-<2y 8 mg 2-<3y 10 mg ≥ 3y 12 mg
![Page 14: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/14.jpg)
14
HA3E
Children < 1y or < 10 kg Cytarabine 67 mg/kg Fludarabine 1 mg/kg Daunoxome 2 mg/kg
Cytarabine 3000 mg/m2 inf (2h)
Etoposide 100 mg/m2 inf (1h)
Day 1-3 every 12 hours
Day 1-5
MTX it
Day 1 5 4 3 2
HA3E
Mtx it age-adjusted <1y 6 mg 1-<2y 8 mg 2-<3y 10 mg ≥ 3y 12 mg
![Page 15: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/15.jpg)
15
FLA
Children < 1y or < 10kg Cytarabine 67 mg/kg Fludarabine 1 mg/kg Daunoxome 2 mg/kg
Fludarabine 30 mg/m2 iv (30min)
Cytarabine 2000 mg/m2 inf (3h)
Day
Day 1-5
Day 1-5 4h after fludarabine
Mtx it
1 5 4 3 2
FLA
Mtx it age-adjusted <1y 6 mg 1-<2y 8 mg 2-<3y 10 mg ≥ 3y 12 mg
![Page 16: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/16.jpg)
16
Day 22 BM after course 1
Repeat BM weekly until recovery of ANC and platelets
Start course 2 immediately
Day 22 BM after course 2
Repeat BM weekly until recovery of PB
Salvage therapy If very aplastic BM consider
repeat BM – see protocol text
LC ≥ 5% LC < 5%
LC ≥ 5%
Start course 2 after recovery
LC < 5%
LC ≥ 5%
LC < 5%
LC < 5% and recovery start HAM
LC ≥ 0.1% assign HR
LC ≥ 5% BM + HAM after recovery
LC before HAM ≥ 0.1% assign HR
LC ≥ 15%
LC < 5%
Assign HR
Assign RD
Flow-sheet induction
![Page 17: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/17.jpg)
17
Radomisation Timepoints
![Page 18: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/18.jpg)
18
Checklist D22 after 1st induction
![Page 19: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/19.jpg)
19
Checklist after 2nd induction
![Page 20: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/20.jpg)
Reference Lab
1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of
this report
20
![Page 21: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/21.jpg)
21
Induction MRD
Standard risk patients MRD before course 5*
Diagnosis – MRD target search
Day 22 – MRD all patients
Good Response < 5% LC MRD repeated weekly
Start course one
Start course two
Poor Response ? 5% LC Course 2 direct
Start course two after regeneration
MRD before consolidation MRD D22
Poor Response Off protocol
Good Response MRD repeated weekly
Start consolidation after regeneration
High risk patients MRD before SCT
High risk patients
MRD before SCT Standard risk patients MRD before course 5*
![Page 22: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/22.jpg)
22
Consolidation MRD
High risk patients MRD before SCT
Standard risk patients MRD before course 5
The exact number of MRD samples cannot be determined but it is expected that 3-4 samples per
patient will be taken during induction
![Page 23: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/23.jpg)
Checklist
23
![Page 24: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/24.jpg)
Sample information sheet
24
![Page 25: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/25.jpg)
Flow Chart
25
![Page 26: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/26.jpg)
Flow Chart
26
![Page 27: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/27.jpg)
27
Database
![Page 29: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/29.jpg)
29
![Page 30: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/30.jpg)
30
SAE/SUSAR reporting
• SAE: toxicity registration (appendix 2) > after each course!
• SUSAR: Death report form (appendix 3) > should be reported within 48h > submitted online in database or by fax
![Page 31: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/31.jpg)
31
![Page 32: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/32.jpg)
32
![Page 33: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/33.jpg)
DAUNOXOME
33
![Page 34: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/34.jpg)
![Page 35: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/35.jpg)
National monitoring is provided by Bimetra Clinics.
Visits: TIV At least 1 visit/site Close-out visit
![Page 36: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/36.jpg)
Responsibilities local sites: Do not start without a signed contract. ◦ Signed contract: UZ Brussel, HUDERF, UZ Leuven, UCL
Contact [email protected] after first inclusion
Contact [email protected] after LPLV Trial Master File SAE/SUSAR reporting: online or fax to NOPHO
Leukaemia registry Please provide us the site specific procedure for
granting access to internet/electronic patient files/…
![Page 37: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/37.jpg)
Trial Master File: See ‘table of contents’ for required
documents ◦ Site signature log ◦ Subject screening and enrolment log ◦ Adverse event log ◦ Medication log ◦ Insurance certificate ◦ …
Templates are available
![Page 38: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/38.jpg)
TIV report - List of responsibilities local PI
- Complete table on page 1: ‘local site’ - Sign the TIV report
- Local investigator - Study personnel
- Send scan to [email protected] - File signed document in TMF
![Page 39: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/39.jpg)
39
Thanks and good luck!
![Page 40: NOPHO-DBH AML 2012 Protocol€¦ · Reference Lab . 1. Review BM cytomorphology 2. Flow cytometry (MRD) 3. Biobanking 4. No PCR 5. No cytogenetics - please send a copy of this report](https://reader033.fdocuments.us/reader033/viewer/2022050604/5fab584e85d87d1df445c524/html5/thumbnails/40.jpg)
40
Conclusions
• NOPHO DBH AML 2012 is open for inclusion: EC approval 17/04/2014
• Intersite contract signed: UZ Brussel, HUDERF, UZ Leuven, UCL
Contact site
Maaike Van Hoecke: 09/332 11 91
Rein Demuynck: 09/332 11 65