A Phase 2 interventional study of Ponatinib 15 MG Oral Tablet in Acute Lymphoblastic Leukemia, Adult, Ph+ ALL and Newly Diagnosed, sponsored by Institute of Hematology and Blood Transfusion, Czech Republic. Terminated at 7 sites in Czechia. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2024-08-14.
Sponsored by Institute of Hematology and Blood Transfusion, Czech Republic · Phase 2, Interventional, and Treatment
This is a phase II interventional trial to evaluate the efficacy of ponatinib plus reduced-intensity chemotherapy in the first-line treatment of adult patients with Ph+ acute lymphoblastic leukemia. This combination has the potential to improve the depth of molecular responses after the induction phase of treatment. Patients who achieve a complete molecular response (CMR) at week 11 will not be directed to alloSCT and will receive consolidation chemotherapy combined with ponatinib, followed by 24 months of ponatinib maintenance. The aim is to spare individuals with a low probability of relapse from overtreatment with more intensive and toxic transplant procedure.
Primary Objective:
To evaluate the percentage of complete molecular responses (CMR) after two cycles of remission induction therapy composed of two cycles of chemotherapy plus ponatinib. CMR is defined as BCR-ABL1 below the Limit of Quantification by Droplet Digital Polymerase Chain Reaction (ddPCR).
Outline:
Pre-phase:
dexamethasone 10 mg/m2 PO (day -5 till -1), cyclophosphamide IV 200 mg/m2 (day -3 till -1), methotrexate 15 mg IT.
Induction I:
ponatinib 30 mg/day PO once daily (QD) continuously since day 1, rituximab 375 mg/m2 IV (day 1), dexamethasone 10 mg/m2 PO (day 1-2, 8-11), vincristine 2 mg IV (day 1, 8, 15), Granulocyte-Colony Stimulating Factor (G-CSF) until recovery.
Induction II:
ponatinib 30 mg/day PO QD continuously, rituximab 375 mg/m2 IV (day 23), cyclophosphamide 1000 mg/m2 IV (day 24), cytarabine 75 mg/m2 IV (day 26-29, 33-36), Granulocyte StimuG-CSF until recovery, methotrexate 15 mg IT (day 26, 33) methotrexate 15 mg + cytarabine 40 mg + dexamethasone 4 mg IT (day 40). Week 11: Primary endpoint assessment.
Consolidation I (week 12):
ponatinib 30 mg/day PO QD continuously, rituximab 375 mg/m2 IV (day 1), dexamethasone 10 mg/m2 PO (day 1-4), vindesine 3 mg/m2 IV (day 2), methotrexate 1.5 g/m2 IV (day 2), cytarabine 2x 2 g/m2 IV (day 5), G-CSF until recovery, methotrexate 15 mg + cytarabine 40 mg + dexamethasone 4 mg IT (day 8). Patients in complete molecular response at week 11 will be treated with 5 additional blocks of chemotherapy followed by maintenance therapy; patients with molecular failure at week 11 will end the study and be directed to alloSCT.
Consolidation II (week 18):
ponatinib 15 mg/day PO QD continuously, rituximab 375 mg/m2 IV (day 1), cyclophosphamide 500 mg/m2 IV (day 2,3), etoposide (VP-16) 75 mg/m2 IV (day 2,3), methotrexate 15 mg + cytarabine 40 mg + dexamethasone 4 mg IT (day 1).
Consolidation III+V (weeks 24 and 36):
ponatinib 15 mg/day PO QD continuously, rituximab 375 mg/m2 IV (day 1), methotrexate 1.5 g/m2 IV (day 2), vincristine 1 mg IV (day 2), 6-mercaptopurine 60 mg/m2 PO (day 2-8), methotrexate 15 mg + cytarabine 40 mg + dexamethasone 4 mg IT at day 1.
Consolidation IV+VI (weeks 30+40):
ponatinib 15 mg/day PO QD continuously, rituximab 375 mg/m2 IV (day 1), dexamethasone 10 mg/m2 PO (day 1-4), cytarabine 1.5 g/m2 IV (day 1+3+5), methotrexate 15 mg + cytarabine 40 mg + dexamethasone 4 mg IT (day 1). Maintenance: ponatinib 15 mg/day PO QD continuously 24 months. (Doses of IV methotrexate and cytarabine are reduced in patients >55 years.)
5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.
This study's enrollment of 4 is below the median of 38 across 4,247 interventional studies indexed under Leukemia.
Browse Leukemia studies →Institute of Hematology and Blood Transfusion, Czech Republic is the lead sponsor of 5 studies on the registry; 2 are open to participants now.
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Exclusion Criteria:
ponatinib plus reduced-intensity chemotherapy in first-line treatment of Adult Ph+ ALL
Drug: Ponatinib 15 MG Oral Tablet
ponatinib plus reduced-intensity chemotherapy in first-line treatment of Adult Ph+ ALL
Also known as: Iclusig, AP24534, L01XE24
Complete Molecular Response
Percentage of patients with Complete Molecular Response (CMR) after 2 cycles of induction therapy composed by reduced chemotherapy and ponatinib. Minimal Residual Disease (MRD) tested by quantification of BCR-ABL1 transcript using ddPCR method
Time frame: At week 11 (acceptable window + 1 wk); after completion of two induction courses and before starting of the 1st Consolidation cycle (each induction course is 23 days with continuing ponatinib treatment till the outcome assessing)
CR and CRi
Complete Remission (CR) and Complete Remission with incomplete blood count recovery(CRi)
Time frame: CR and CRi at the end of the 1st Induction Course (Day 23) and at week 11 (acceptable window + 1wk) after completion of the 2nd Induction Course and before starting of the 1st Consolidation Cycle
PFS
Progression Free Survival (PFS)
Time frame: Time from the day of CR/CRi documentation until the date of relapse, or death from any cause whichever came first, assessed up to 36 months
OS
Overall Survival (OS)
Time frame: Time from the day 1 (starting of the 1st Induction Course) until the date of death from any cause, assessed up to 36 months
AlloSCT in the first complete remission
Percentage of patients with suboptimal molecular response after completion of 2 induction course containing ponatinib
Time frame: At week 11 (acceptable window + 1 wk); after completion of two induction courses and before starting of the 1st Consolidation cycle (each induction course is 23 days with continuing ponatinib treatment till the outcome assessing)
Severity and occurence of adverse events related to ponatinib
Severity and occurence of adverse events related to ponatinib treatment
Time frame: During the ponatinib treatment up to 30 days after end of treatment
Plan to share: No
This study is terminated, as verified in Aug 2023. You cannot join it, but the record below documents what was studied.
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Institute of Hematology and Blood Transfusion, Czech Republic