Ponatinib With Chemotherapy for Young Adults Ph Positive Acute Lymphoblastic Leukemia

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).

Conditions

• ALL

Interventions

DRUG

Prednisone

Prednisone 60 mg/m2/day IV over 7 days (-7 a -1) and triple intrathecal therapy (TIT)

DRUG

Vincristine

Vincristine (VCR): 1.5 mg/m2 (maximum 2 mg) IV days 1, 8, 15 and 22.

DRUG

Daunorubicin

Daunorubicin (DNR): 45 mg/m2 IV days 1, 8, 15 and 22.

DRUG

Prednisone

Prednisone (PDN): 60 mg/m2/day, IV or PO, days 1 to 27.

DRUG

Ponatinib

Ponatinib 30 mg, PO from day 1 to consolidation

DRUG

Mercaptopurine

Mercaptopurine (MP): 50 mg/m2, PO days 1 to 7, 28 to 35 and 56 to 63.

DRUG

Methotrexate

MTX: 1,5 g/m2, IV (24 h continuous infusion) days 1, 28 and 56

DRUG

VP-16

VP-16: 100 mg/m2/12 h, IV, days 14 and 42

DRUG

ARA-C:

ARA-C: 1000 mg/m2/12 h, IV, days 14-15 and 42-43.

DRUG

TIT

TIT (MTX: 12 mg, ARA-C: 30 mg, hydrocortisone: 20 mg), , days 1, 28 and 56.

DRUG

Ponatinib

Ponatinib 30 mg/d PO, from day 1 to 15 days before HSCT.

PROCEDURE

Autologous transplantation

Myeloablative conditioning with cyclophosphamide and total body irradiation (TBI) whenever possible and autologous transplantation

PROCEDURE

Allo transplantation

Myeloablative conditioning with cyclophosphamide and total body irradiation (TBI) whenever possible and allo transplantation

Sponsors & Collaborators

• PETHEMA Foundation

  lead OTHER

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-06-30

Primary Completion

2020-08-05

Completion

2023-08-31

Countries

• Spain

Study Locations