A Phase I/II Study of the Combination of Venetoclax, Ponatinib and Corticosteroids in Patients With Relapsed or Refractory Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia and Lymphoid Blast Phase Chronic Myelogenous Leukemia
-
- STATUS
- Recruiting
-
- days left to enroll
- 3
-
- participants needed
- 38
-
- sponsor
- M.D. Anderson Cancer Center
Summary
This phase I/II trial studies the best dose of venetoclax when given together with ponatinib and dexamethasone and to see how well they work in treating participants with Philadelphia chromosome or BCR-ABL positive acute lymphoblastic leukemia or chronic myelogenous leukemia that has come back or does not respond to treatment. Drugs used in chemotherapy, such as venetoclax and dexamethasone, 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. Ponatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving venetoclax, ponatinib, and dexamethasone may work better in treating participants with acute lymphoblastic leukemia or chronic myelogenous leukemia.
Description
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of venetoclax, ponatinib, and dexamethasone in patients with relapsed/refractory Philadelphia positive (Ph+) acute lymphoblastic leukemia (ALL) or lymphoid blastic phase (BP)-chronic myelogenous leukemia (CML). (Phase I) II. To determine the efficacy of the regimen, as defined by the rate of complete remission (CR) or CR with incomplete count recovery (CRi). (Phase II)
SECONDARY OBJECTIVES:
I. To determine efficacy outcomes, including rate of minimal residual disease negativity by polymerase chain reaction (PCR) for BCR-ABL1 transcripts, median relapse-free survival (RFS), and median overall survival (OS).
II. To determine the proportion of patients proceeding to allogeneic stem cell transplant (ASCT).
III. To preliminarily determine the safety of the combination regimen.
EXPLORATORY OBJECTIVES:
I. To evaluate the effect of single-agent ponatinib on apoptotic proteins and Bcl-2 dependency.
II. To correlate apoptotic protein expression and Bcl-2 dependency on response and resistance to the combination regimen.
III. To assess impact of baseline genomics on outcomes with the combination regimen.
OUTLINE: This is a phase I, dose-escalation study of venetoclax followed by a phase II study.
INDUCTION (COURSE 1): Participants who have not received ponatinib within 2 weeks of the anticipated start date receive ponatinib orally (PO) daily on days 1-35, venetoclax PO daily on days 8-35, and dexamethasone PO or intravenously (IV) over 15 minutes on days 8-11. Participants who have received ponatinib within 2 weeks of the anticipated start date receive ponatinib PO and venetoclax PO daily on days 1-28 and dexamethasone PO or IV over 15 minutes on days 1-4. Participants with CD20 expression receive rituximab IV over 2-6 hours on days 14 and 21 at the discretion of the treating physician after the maximum dose of venetoclax has been reached.
CONSOLIDATION (COURSES 2-4): Participants receive ponatinib PO and venetoclax PO daily on days 1-28 and dexamethasone PO or IV over 15 minutes on days 1-4. Participants with CD20 expression receive rituximab IV over 2-6 hours for up to 2 doses each course at the discretion of the treating physician after the maximum dose of venetoclax has been reached. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE (COURSES 5+): Participants receive ponatinib PO and venetoclax PO daily on days 1-28 and dexamethasone PO or IV over 15 minutes on days 1-4. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. Participants achieving remission undergo ASCT at the discretion of the treating physician.
After completion of study treatment, participants are followed up at 30 days.
Details
| Condition | Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Philadelphia Chromosome Positive, Recurrent Acute Lymphoblastic Leukemia, Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Refractory Acute Lymphoblastic Leukemia, Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive, t(9;22) |
|---|---|
| Treatment | Rituximab, methotrexate, cytarabine, Dexamethasone, Ponatinib, venetoclax, Ponatinib Hydrochloride |
| Clinical Study Identifier | NCT03576547 |
| Sponsor | M.D. Anderson Cancer Center |
| Last Modified on | 22 October 2022 |
How to participate?
,
You have contacted , on
Your message has been sent to the study team at ,
What happens next?
- You can expect the study team to contact you via email or phone in the next few days.
- Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.
You are contacting
Primary Contact
Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.
Learn moreIf you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
Learn moreComplete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.
Learn moreSimilar trials to consider
Browse trials for
Not finding what you're looking for?
Sign up as a volunteer to stay informed
Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.
Sign up as volunteer