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).
Timeline
- Start
- 2016-06
- Primary completion
- 2020-08-05
- Completion
- 2023-08
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Ponatinib | Small molecule | 30 mg | Oral |
| Background | Cytarabine | Small molecule | 30 mg | Intravenous |
| Background | Cytarabine | Small molecule | 1000 mg/m2 | Intravenous |
| Background | Daunorubicin | Small molecule | 45 mg/m2 | Intravenous |
| Background | Etoposide | Small molecule | 100 mg/m2 | Intravenous |
| Background | Hydrocortisone | Other / unclassified | 20 mg | Intrathecal |
| Background | MERCAPTOPURINE ANHYDROUS | Small molecule | 40 mg/m2 | Oral |
| Background | MERCAPTOPURINE ANHYDROUS | Small molecule | 50 mg/m2 | Oral |
| Background | Methotrexate | Small molecule | 12 mg | Intravenous |
| Background | Methotrexate | Small molecule | 15 mg/m2 | Intravenous |
| Background | Methotrexate | Small molecule | 1.5 g | Intravenous |
| Background | Prednisone | Other / unclassified | 60 mg/m2 | Intravenous |
| Background | Vincristine | Small molecule | 1.5 mg/m2 | Intravenous |
Indications
No indication recorded.