Ponatinib + Chemotherapy for Acute Lymphoblastic Leukemia

Recruiting in Palo Alto (17 mi)

+77 other locations

Age: < 65

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Takeda

No Placebo Group

Approved in 3 jurisdictions

Trial Summary

What is the purpose of this trial?This study is about an anticancer drug called ponatinib which is a tyrosine kinase inhibitor given with chemotherapy to children, teenagers, and young adults up to 21 years of age with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia who have relapsed or are resistant to other treatment. The main aims of this study are to confirm the highest dose of ponatinib tablets and minitablet capsules that can be given to participants with acceptable side effects, and to evaluate if participant's leukemia achieves remission. Participants will take ponatinib tablets with chemotherapy. For participants who cannot swallow tablets or who are receiving less than a 10 milligrams (mg) dose, a capsule with small ponatinib minitablets inside will be provided. Participants will take ponatinib for 10 weeks in combination with chemotherapy (reinduction and consolidation blocks) and will be followed up for at least 3 years.

Eligibility Criteria

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.

Inclusion Criteria

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

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

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

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

My leukemia is positive for a specific genetic change.

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

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

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

My leukemia has specific genetic changes.

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

I am mostly able to carry out daily activities.

Exclusion Criteria

I have a significant brain condition.

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

I have no GI conditions that affect medication absorption.

I have seizures that are not controlled by medication.

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

I have been treated with ponatinib before.

I have or had chronic myeloid leukemia.

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

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

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

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

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

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

My high blood pressure is not under control.

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

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

I have a serious heart condition.

Participant Groups

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.

1Treatment groups

Experimental Treatment

Group I: PonatinibExperimental Treatment2 Interventions

Ponatinib tablets, based on 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.

Ponatinib is already approved in United States, European Union, Canada for the following indications:

🇺🇸 Approved in United States as Iclusig for: