Clinical Trial Details
— Status: Active, not recruiting
Administrative data
NCT number |
NCT02776605 |
Other study ID # |
PONALFIL |
Secondary ID |
|
Status |
Active, not recruiting |
Phase |
Phase 2
|
First received |
|
Last updated |
|
Start date |
June 2016 |
Est. completion date |
August 2023 |
Study information
Verified date |
February 2022 |
Source |
PETHEMA Foundation |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Evaluate the response (complete hematologic response [CHR], complete cytogenetic response
[CCyR], major molecular response [MMR] and complete molecular response [CMR] of the
combination of ponatinib with standard chemotherapy (according to PETHEMA ALL Ph08 trial) in
young patients with Ph+ (BCR-ABL) ALL.
All patients are treated with:
Pre-phase (maximum 7 days, -7 to -1):
Prednisone 60 mg/m2/day IV over 7 days (-7 a -1) and triple intrathecal therapy (TIT)
(Methotrexate [MTX]: 12 mg, ARA-C: 30 mg, hydrocortisone: 20 mg). 2. Induction (day 1 to day
28 or up to hematological recovery) Vincristine (VCR): 1.5 mg/m2 (maximum 2 mg) IV days 1, 8,
15 and 22. Daunorubicin (DNR): 45 mg/m2 IV days 1, 8, 15 and 22. Prednisone (PDN): 60
mg/m2/day, IV or PO, days 1 to 27. Ponatinib 30 mg, PO from day 1 to consolidation. TIT, days
1 and 22. 3. Consolidation (day 1 to day 63) Mercaptopurine (MP): 50 mg/m2, PO days 1 to 7,
28 to 35 and 56 to 63. MTX: 1,5 g/m2, IV (24 h continuous infusion) days 1, 28 and 56. VP-16:
100 mg/m2/12 h, IV, days 14 and 42. ARA-C: 1000 mg/m2/12 h, IV, days 14-15 and 42-43. TIT
(MTX: 12 mg, ARA-C: 30 mg, hydrocortisone: 20 mg), , days 1, 28 and 56. Ponatinib 30 mg/d PO,
from day 1 to 15 days before HSCT. 4. HSCT (performed ideally within 1 month from the end of
consolidation). AlloHSCT preferred over autoHSCT (autoHSCT only indicated if alloHSCT not
feasible). Myeloablative conditioning with cyclophosphamide and total body irradiation (TBI)
whenever possible. 5. Post HSCT therapy After alloHSCT. Frequent monitoring of MRD (every
month). I After autoHSCT: Frequent monitoring of MRD (every month).
Description:
Objectives Primary
1. To evaluate the response (complete hematologic response [CHR], complete cytogenetic
response [CCyR], major molecular response [MMR] and complete molecular response [CMR] of
the combination of ponatinib with standard chemotherapy (according to PETHEMA ALL Ph08
trial) in young patients with Ph+ (BCR-ABL) ALL.
2. To evaluate the event free survival (EFS) of the combination of ponatinib with standard
chemotherapy (according to PETHEMA ALL Ph08 trial) in young patients with Ph+ (BCR-ABL)
ALL. Secondary
- To evaluate the rate of patients receiving an allogeneic hematopoietic stem cell
transplant (alloHSCT) in first CR
- To evaluate the frequency of MMR and CMR at the time of alloHSCT
- To evaluate the transplant-related mortality (TRM)
- To evaluate the CR duration and overall survival (OS) of the combination of
ponatinib with standard chemotherapy (according to PETHEMA ALL Ph08 trial) in young
patients with Ph+ (BCR-ABL) ALL.
- To evaluate the outcome measures (CR duration, OS and EFS) in context of those
observed in the PETHEMA ALL Ph08 trial.
- To observe the type and number of BCR-ABL kinase domain mutations developing during
and after the study.
- To evaluate side effects, adverse events (AE) and serious AE (SAE).
Interventions:
1. Pre-phase (maximum 7 days, -7 to -1):
Prednisone 60 mg/m2/day IV over 7 days (-7 a -1) and triple intrathecal therapy (TIT)
(Methotrexate [MTX]: 12 mg, ARA-C: 30 mg, hydrocortisone: 20 mg).
2. Induction (day 1 to day 28 or up to hematological recovery) Vincristine (VCR): 1.5 mg/m2
(maximum 2 mg) IV days 1, 8, 15 and 22. Daunorubicin (DNR): 45 mg/m2 IV days 1, 8, 15
and 22. Prednisone (PDN): 60 mg/m2/day, IV or PO, days 1 to 27. Ponatinib 30 mg, PO from
day 1 to consolidation. TIT, days 1 and 22.
3. Consolidation (day 1 to day 63) Mercaptopurine (MP): 50 mg/m2, PO days 1 to 7, 28 to 35
and 56 to 63. MTX: 1,5 g/m2, IV (24 h continuous infusion) days 1, 28 and 56. VP-16: 100
mg/m2/12 h, IV, days 14 and 42. ARA-C: 1000 mg/m2/12 h, IV, days 14-15 and 42-43. TIT
(MTX: 12 mg, ARA-C: 30 mg, hydrocortisone: 20 mg), , days 1, 28 and 56. Ponatinib 30
mg/d PO, from day 1 to 15 days before HSCT.
4. HSCT (performed ideally within 1 month from the end of consolidation). AlloHSCT
preferred over autoHSCT (autoHSCT only indicated if alloHSCT not feasible).
Myeloablative conditioning with cyclophosphamide and total body irradiation (TBI)
whenever possible.
5. Post HSCT therapy After alloHSCT. Frequent monitoring of MRD (every month). If MRD
negative: no therapy. If MRD positive, Ponatinib 30 mg/d, po, until 2 yr. after HSCT.
The ponatinib dose will be reduced to 15 mg/d in the second year in patients with
sustained molecular response. After autoHSCT: Frequent monitoring of MRD (every month).
All patients will receive Ponatinib: 30 mg/d, PO, mercaptopurine, (40 mg/m2/d, PO) and
methotrexate (15 mg/m2/week, IM), during the first year after HSCT. The ponatinib dose
will be reduced to 15 mg/d in the second year in patients with sustained molecular
response.