Ignite Creation Date:
2025-12-26 @ 10:17 PM
Ignite Modification Date:
2026-03-10 @ 6:47 AM
Study NCT ID:
NCT03147612
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-08-13
First Post:
2017-05-05
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Low-Intensity Chemotherapy, Ponatinib and Blinatumomab in Treating Patients With Philadelphia Chromosome-Positive and/or BCR-ABL Positive Acute Lymphoblastic Leukemia
Sponsor:
M.D. Anderson Cancer Center
Organization:
Study Overview
Official Title:
Phase II Study of the Sequential Combination of Low-Intensity Chemotherapy and Ponatinib Followed by Blinatumomab and Ponatinib in Patients With Philadelphia Chromosome (Ph)-Positive and/or BCR-ABL Positive Acute Lymphoblastic Leukemia (ALL)
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase II trial studies how well low-intensity chemotherapy and ponatinib work in treating patients with Philadelphia chromosome-positive and/or BCR-ABL positive acute lymphoblastic leukemia that may have come back or is not responding to treatment. Drugs used in chemotherapy, such as cyclophosphamide, vincristine, dexamethasone, methotrexate, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with rituximab and blinatumomab, may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Ponatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Granulocyte colony stimulating factor helps the bone marrow make recover after treatment. Giving low-intensity chemotherapy, ponatinib, and blinatumomab may work better in treating patients with acute lymphoblastic leukemia.
Detailed Description:
PRIMARY OBJECTIVES:
I. To evaluate the complete molecular response (CMR) rate of ponatinib and blinatumomab in combination with low-intensity chemotherapy in patients with newly diagnosed Philadelphia chromosome (Ph)-positive and/or BAR-ABL-positive acute lymphoblastic leukemia (ALL). (Cohort 1) II. To evaluate the overall response (OR; complete response \[CR\] + complete response with hematologic improvement \[CRi\]) in patients with relapsed/refractory disease. (Cohort 2)
SECONDARY OBJECTIVES:
I. To evaluate other clinical efficacy endpoints (complete cytogenetic response, complete molecular response \[CMR\] \[for relapsed/refractory population\], event-free survival and overall survival) and safety of the combination regimen.
EXPLORATORY OBJECTIVES:
I. To characterize the role of ABL1 kinase domain mutations on treatment failure and relapse in patients with Ph+ ALL treated with hyper-CVD plus ponatinib and blinatumomab.
II. To determine the impact of recurrent genomic alterations and ribonucleic acid (RNA) expression at diagnosis on relapse free survival (RFS) in patients with Ph+ ALL treated with hyper-CVD plus ponatinib and blinatumomab.
III. To investigate the impact of next-generation sequencing-based minimal residual disease assessment on relapse-free survival in patients with Ph+ ALL.
IV. To determine the effect on immune cell subsets in patients with Ph+ ALL treated with blinatumomab plus ponatinib.
OUTLINE:
CYCLES 1 and 3: Patients receive ponatinib orally (PO) once daily (QD) on days 1-21 of cycle 1 and on days 1-28 of subsequent cycles, cyclophosphamide intravenously (IV) twice daily (BID) over 3 hours on days 1-3, rituximab IV over 4-6 hours on days 1 and 11, vincristine IV over 15 minutes on days 1 and 11, and pegfilgrastim or filgrastim subcutaneously (SC) daily on day 4. Patients also receive methotrexate intrathecally via spinal tap on day 2 and cytarabine intrathecally on day 7 in the absence of disease progression or unacceptable toxicity.
CYCLES 2 and 4: Patients receive ponatinib PO QD on days 1-28, methotrexate IV over 24 hours on day 1 and intrathecally on day 8, cytarabine IV BID over 2-3 hours on days 2 and 3 and intrathecally on day 5, pegfilgrastim or filgrastim SC daily on day 4, and rituximab IV over 4-6 hours on days 1 and 8 in the absence of disease progression or unacceptable toxicity.
CYCLES 5-8: Patients receive blinatumomab via central catheter continuously over weeks 1-4 every 6 weeks. Patients also receive methotrexate intrathecally on day 1 of cycle 5 and on day 8 of cycle 6 and cytarabine intrathecally on day 7 of cycle 5 and on day 1 of cycle 6 in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY:
CYCLES 1-3, 5-7, 9-11, and 13-15: After 4 cycles of blinatumomab, if disease has not gotten worse, patients receive vincristine IV over 15 minutes on day 1, prednisone PO on days 1-5, and ponatinib PO QD on days 1-28.
CYCLES 4, 8, and 12: Patients receive blinatumomab via central catheter continuously over weeks 1-4 every 6 weeks and ponatinib PO QD on days 1-28.
Treatment repeats every 28 days for up to 15 cycles in the absence of disease progression or unacceptable toxicity. Patients unable to receive blinatumomab, you may receive maintenance therapy with vincristine, prednisone, and ponatinib for a total of about 24 cycles at the discretion of doctor.
POST-MAINTENANCE THERAPY: Patients receive ponatinib PO QD on days 1-28. Cycles repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 6 months thereafter.
I. To evaluate the complete molecular response (CMR) rate of ponatinib and blinatumomab in combination with low-intensity chemotherapy in patients with newly diagnosed Philadelphia chromosome (Ph)-positive and/or BAR-ABL-positive acute lymphoblastic leukemia (ALL). (Cohort 1) II. To evaluate the overall response (OR; complete response \[CR\] + complete response with hematologic improvement \[CRi\]) in patients with relapsed/refractory disease. (Cohort 2)
SECONDARY OBJECTIVES:
I. To evaluate other clinical efficacy endpoints (complete cytogenetic response, complete molecular response \[CMR\] \[for relapsed/refractory population\], event-free survival and overall survival) and safety of the combination regimen.
EXPLORATORY OBJECTIVES:
I. To characterize the role of ABL1 kinase domain mutations on treatment failure and relapse in patients with Ph+ ALL treated with hyper-CVD plus ponatinib and blinatumomab.
II. To determine the impact of recurrent genomic alterations and ribonucleic acid (RNA) expression at diagnosis on relapse free survival (RFS) in patients with Ph+ ALL treated with hyper-CVD plus ponatinib and blinatumomab.
III. To investigate the impact of next-generation sequencing-based minimal residual disease assessment on relapse-free survival in patients with Ph+ ALL.
IV. To determine the effect on immune cell subsets in patients with Ph+ ALL treated with blinatumomab plus ponatinib.
OUTLINE:
CYCLES 1 and 3: Patients receive ponatinib orally (PO) once daily (QD) on days 1-21 of cycle 1 and on days 1-28 of subsequent cycles, cyclophosphamide intravenously (IV) twice daily (BID) over 3 hours on days 1-3, rituximab IV over 4-6 hours on days 1 and 11, vincristine IV over 15 minutes on days 1 and 11, and pegfilgrastim or filgrastim subcutaneously (SC) daily on day 4. Patients also receive methotrexate intrathecally via spinal tap on day 2 and cytarabine intrathecally on day 7 in the absence of disease progression or unacceptable toxicity.
CYCLES 2 and 4: Patients receive ponatinib PO QD on days 1-28, methotrexate IV over 24 hours on day 1 and intrathecally on day 8, cytarabine IV BID over 2-3 hours on days 2 and 3 and intrathecally on day 5, pegfilgrastim or filgrastim SC daily on day 4, and rituximab IV over 4-6 hours on days 1 and 8 in the absence of disease progression or unacceptable toxicity.
CYCLES 5-8: Patients receive blinatumomab via central catheter continuously over weeks 1-4 every 6 weeks. Patients also receive methotrexate intrathecally on day 1 of cycle 5 and on day 8 of cycle 6 and cytarabine intrathecally on day 7 of cycle 5 and on day 1 of cycle 6 in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY:
CYCLES 1-3, 5-7, 9-11, and 13-15: After 4 cycles of blinatumomab, if disease has not gotten worse, patients receive vincristine IV over 15 minutes on day 1, prednisone PO on days 1-5, and ponatinib PO QD on days 1-28.
CYCLES 4, 8, and 12: Patients receive blinatumomab via central catheter continuously over weeks 1-4 every 6 weeks and ponatinib PO QD on days 1-28.
Treatment repeats every 28 days for up to 15 cycles in the absence of disease progression or unacceptable toxicity. Patients unable to receive blinatumomab, you may receive maintenance therapy with vincristine, prednisone, and ponatinib for a total of about 24 cycles at the discretion of doctor.
POST-MAINTENANCE THERAPY: Patients receive ponatinib PO QD on days 1-28. Cycles repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 6 months thereafter.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: