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Tyrosine Kinase Inhibitor

Ponatinib + Chemotherapy for Acute Lymphoblastic Leukemia

Phase 1 & 2

Waitlist Available

Research Sponsored by Takeda

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

HSCT: Participants who have experienced relapse after a HSCT are eligible, provided they have no evidence of acute or chronic graft-versus-host disease (GVHD), are not receiving GVHD prophylaxis or treatment, and are at least 90 days posttransplant at the time of enrollment.

a) Involvement of BM with ALL, including one of the following: i. M2 BM (5%-24% lymphoblasts): by morphology with confirmatory testing consisting of at least one of the following: flow cytometry lymphoblasts ≥5%, or BCR-ABL1 fluorescence in situ hybridization, or ≥10-2 leukemic clone identified by immunoglobulin heavy chain-T-cell receptor polymerase chain reaction, OR ii. M3 BM (≥25% lymphoblasts): by morphology, OR iii. Participants with combined BM (as defined above) and extramedullary disease.

Must not have

Participants with pre-existing significant CNS pathology

Participants with a history of cerebrovascular ischemia/hemorrhage with residual deficits

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 36 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing an anticancer drug called ponatinib, given with chemotherapy, to children, teenagers, and young adults up to 21 years of age with leukemia that has relapsed or is resistant to other treatment.

Who is the study for?

This trial is for children, teenagers, and young adults up to age 21 with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia who have not responded well to other treatments or have a specific mutation (BCR-ABL1 T315I). They should be able to perform daily activities at least half of the time (Karnofsky/Lansky score ≥50%) and recovered from previous treatment side effects. Those with another cancer, uncontrolled health conditions like hypertension or seizures, recent use of certain drugs affecting liver enzymes, or history of severe blood disorders cannot join.

What is being tested?

The study tests ponatinib tablets/capsules combined with chemotherapy in participants who either can't swallow pills or need smaller doses. The goal is to find the highest safe dose that might help achieve leukemia remission. Participants will take this combination for 10 weeks alongside standard chemotherapy blocks and will be monitored for at least three years.

What are the potential side effects?

Ponatinib may cause cardiovascular issues like high blood pressure or heart problems; it could also affect liver function and increase the risk of bleeding events. Other possible side effects include fatigue, digestive disturbances, skin reactions, headaches, joint pain and an increased risk of infections.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I had a stem cell transplant, no GVHD, not on GVHD treatment, and it's been 90 days since.

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My leukemia involves bone marrow with specific levels of lymphoblasts or extramedullary disease.

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I stopped my last cancer treatment due to severe side effects.

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I have been diagnosed with a specific type of leukemia linked to the Philadelphia chromosome.

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My leukemia is positive for a specific genetic change.

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I have recovered from side effects of my previous treatment, except for hair loss.

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My previous cancer treatment, which targeted a specific protein, did not work or caused side effects I couldn't tolerate.

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I am mostly capable of self-care and daily activities.

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My leukemia has specific genetic changes.

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My leukemia has spread to my bone marrow and possibly other areas.

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I am mostly able to carry out daily activities.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a significant brain condition.

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I have had a stroke or brain bleed that left me with lasting effects.

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I have no GI conditions that affect medication absorption.

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I have seizures that are not controlled by medication.

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I am not planning to receive any other cancer treatments while on this study.

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I have been treated with ponatinib before.

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I have or had chronic myeloid leukemia.

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I am currently taking medication that can affect my heart's rhythm.

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I have not received any live vaccines in the last 30 days.

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I have or had Burkitt leukemia/lymphoma or mature B-cell leukemia.

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I do not have an uncontrolled infection or active HIV, hepatitis B, or C.

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I was diagnosed with a specific type of leukemia after receiving chemotherapy for another cancer.

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I have been diagnosed with another type of cancer at the same time.

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My high blood pressure is not under control.

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I have a genetic condition like Fanconi anemia or Bloom syndrome.

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I have had serious blood clotting or heart/blood vessel problems.

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I have a serious heart condition.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 36 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 36 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 36 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase 1: Recommended Phase 2 Dose (RP2D) of Ponatinib in Combination With Chemotherapy

Phase 2: Complete Remission (CR) Rate at the end of Reinduction Block

Secondary study objectives

Phase 1: CR Rate at the end of Reinduction Block

Phase 2: Duration of Response (DOR)

Phase 2: Event-free Survival (EFS)

+4 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: PonatinibExperimental Treatment3 Interventions

Ponatinib tablet or age appropriate formulation (AAF) \[i.e., capsules with ponatinib minitablets\], based on age and weight, in combination with chemotherapy backbone, orally, once daily in both reinduction block and consolidation block (35 days each including 29 days of treatment followed by rest period from chemotherapy for a minimum of 6 days consisting of daily ponatinib only) in Phase 1 to determine RP2D. In Phase 2 participants will receive ponatinib at RP2D in combination with chemotherapy backbone.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ponatinib

2015

Completed Phase 2

~830

Chemotherapy Agents

2021

Completed Phase 2

~20