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A Study of Ponatinib With Chemotherapy in Children, Teenagers, and Adults With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia | Clinical Trials | Clareo Health

TERMINATEDPHASE1/PHASE2

A Study of Ponatinib With Chemotherapy in Children, Teenagers, and Adults With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

A Pivotal Phase 1/2, Single-Arm, Open-label Study to Evaluate the Safety and Efficacy of Ponatinib With Chemotherapy in Pediatric Patients With Philadelphia Chromosome-Positive (Ph+) Acute Lymphoblastic Leukemia (ALL) Who Have Relapsed or Are Resistant or Intolerant to a Prior Tyrosine Kinase Inhibitor-Containing Therapy, or Who Have the T315I Mutation

NCT04501614•Takeda

View on ClinicalTrials.gov

Summary

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.

Detailed Description

The drug being tested in this study is called ponatinib. Ponatinib is being tested to treat pediatric population who have Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), Ph+ mixed phenotype acute leukemia (Ph+ MPAL), or Philadelphia chromosome-like ALL who have relapsed or are resistant or intolerant to a prior tyrosine kinase inhibitor (TKI)-containing therapy, or who have the T315I mutation. The study will enroll approximately 68 participants. Participants will be assigned to a treatment group either in phase 1 or phase 2. Participants unable to swallow the ponatinib tablets or who are receiving less than a 10 mg dose will receive the age-appropriate formulation, capsule with ponatinib minitablets inside: • Ponatinib + Chemotherapy All participants will be asked to take ponatinib once daily. In phase 1 ponatinib will be administered in combination with a chemotherapy backbone to determine the recommended phase 2 dose (RP2D) of ponatinib. In both phase 1 and phase 2, treatment consists of two 35-day blocks of therapy (reinduction block and consolidation block). Each block will include 29 days of treatment of daily ponatinib and a chemotherapy backbone regimen followed by a rest period from chemotherapy for a minimum of 6 days consisting of daily ponatinib only. This is a multi-center trial and will be conducted worldwide. The overall time to participate in this study is 6.5 years. Participants will make multiple visits to the clinic, and may be contacted by telephone in at least 36 months of follow-up after treatment.

Eligibility

Age

1 - 21 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Participants must have a diagnosis of Ph+ ALL, Philadelphia chromosome-positive plus mixed phenotype acute leukemia (Ph+ MPAL), or Ph-like ALL with:
•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.
•b) Evidence of Ph+ ALL, MPAL, or Ph-like ALL: i. Definite evidence of BCR-ABL1 fusion (Ph) for Ph+ ALL and MPAL, OR ii. Definite evidence of Ph-like ALL with targetable kinase-activating lesions involving any of the following kinase genes: ABL1, ABL2, CSF1R, and PDGFRB.
•Ph-like ALL diagnosis requires the identification of specified targetable kinase-activating lesions preferably by ribonucleic acid (RNA) sequencing or by alternative accredited method used by the site.
•c) Disease status: (i) For non-US sites: participants who have relapsed (post 0 or 1 HSCT) or are resistant or intolerant to at least one prior therapy that contained a BCR-ABL-targeted tyrosine kinase inhibitor (TKI), or for US sites: participants who have relapsed (post 0 or 1 HSCT) or are resistant or intolerant to at least one prior therapy that contained a second-generation BCR-ABL1-targeted TKI (i.e, dasatinib, nilotinib, and bosutinib); OR (ii) Have a BCR-ABL1 T315I mutation irrespective of relapse, resistance/intolerance, or transplant status and irrespective of any prior TKI use.
•Notes:
•A participant will be defined as intolerant if they had a Grade ≥3 nonhematologic toxicity or a Grade 4 hematologic toxicity considered related to the last TKI and lasting for \>2 weeks, and led to discontinuation of therapy.
•2. Weight: Participants must be weighing at least 5 kg at the time of enrollment.
•3. Performance Status: Karnofsky performance status ≥50% for participants ≥16 years of age or Lansky Play Scale ≥50% for participants \<16 years of age.
•4. Have recovered to less than Grade 2 National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) Version 5.0, or to baseline, from any nonhematologic toxicities (except alopecia) due to previous therapy.
+18 more criteria

Exclusion Criteria

•1. A history or current diagnosis of Burkitt leukemia/lymphoma or mature B-cell leukemia.
•2. A history or current diagnosis of chronic myeloid leukemia (CML).
•3. Diagnosis of ALL, MPAL, or Ph-like ALL with targetable kinase-activating lesions after treatment with cytotoxic therapy for another cancer.
•4. Diagnosis of another concurrent primary malignancy.
•5. Clinically significant cardiovascular disease, including but not limited to:
•1. Any history of myocardial infarction (MI) or unstable angina.
•2. History of or presence of heart block, and/or clinically significant ventricular or atrial arrhythmias.
•3. Uncontrolled hypertension, defined as persistent elevation of systolic and/or diastolic blood pressures to ≥95th percentile based on age, sex, and height percentiles despite appropriate antihypertensive management.
•6. Current systemic use of drug(s) that are known to have a risk of causing prolonged corrected QT interval (QTc) or torsades de pointes unless drug(s) can be changed to acceptable alternatives (ie, an alternate class of agents that do not affect the cardiac conduction system) or the participants can safely discontinue the drug(s).
•7. Uncontrolled hypertriglyceridemia (triglycerides ≥450 milligrams per deciliter (mg/dL)).
+10 more criteria

Locations (64)

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

Rady Childrens Hospital San Diego - PIN

San Diego, California, United States

UCSF Medical Comprehensive Cancer

San Francisco, California, United States

Alfred I Dupont Hospital For Children

Wilmington, Delaware, United States

Ann and Robert H Lurie Childrens Hospital of Chicago

Chicago, Illinois, United States

Riley Hospital For Children

Indianapolis, Indiana, United States

Children's Mercy Hospital and Clinica

Kansas City, Missouri, United States

Cincinnati Children's Hospital Medical Center - PIN

Cincinnati, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Key Dates

Start Date

February 24, 2021

Primary Completion Date

December 19, 2023

Completion Date

July 19, 2024

Last Updated

October 2, 2025

Enrollment

ACTUAL participants

Conditions

Pediatric Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia (Ph+ALL)Ph+ Mixed Phenotype Acute Leukemia (MPAL)Philadelphia Chromosome-Like ALL (Ph-like ALL)

Interventions

Ponatinib

DRUG

Chemotherapy Agents

DRUG