for people ages 1-21 (full criteria)
study started
estimated completion
Principal Investigator
by Mignon Loh (ucsf)
Photo of Mignon Loh
Mignon Loh



The purpose of the study is to determine the recommended phase 2 dose (RP2D) of ponatinib (tablet and age-appropriate formulation [AAF]) in combination with chemotherapy in Phase 1 and the efficacy of ponatinib in combination with chemotherapy as measured by the rate of complete remission (CR) at the end of the reinduction block at the RP2D.

Official Title

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


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) 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 patients. Participants will be assigned to a treatment group either in phase 1 or phase 2. Participants unable to swallow the ponatinib tablets will receive the age-appropriate formulation, minitablets: • 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 36 months. Participants will make multiple visits to the clinic, and may be contacted by telephone in follow-up after treatment.


Pediatric Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia (Ph+ALL) Ph+ Mixed Phenotype Acute Leukemia (MPAL) Drug Therapy Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Philadelphia Chromosome Ponatinib Ponatinib AAF Chemotherapy Agents


You can join if…

Open to people ages 1-21

  1. Have a diagnosis of acute lymphoblastic leukemia (ALL) or mixed phenotype acute leukemia (MPAL) with definite evidence of breakpoint cluster region- Abelson 1 (BCR-ABL1) fusion (Ph) or Ph-like ALL (USA-only) with targetable kinase-activating lesions and either (i) or (ii) as follows: (i) For non-US sites: participants who have relapsed 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 or are resistant or intolerant to at least one prior therapy that contained a second-generation BCR-ABL1-targeted TKI (ie, dasatinib, nilotinib, and bosutinib); or (ii) have a T315I mutation. Note: A participant will be defined as intolerant if they had a Grade ≥3 nonhematologic toxicity or a Grade 4 hematologic toxicity considered at least possibly related to the last TKI and lasting for >2 weeks, and led to discontinuation of therapy. Eligible participants include:

  1. Participants in relapse (post 0 or 1 hematopoietic stem cell transplantation (HSCT)).
  2. Participants with BCR-ABL1 T315I mutation, irrespective of relapse, resistance/intolerance, or transplant status and irrespective of any prior TKI use.
  3. Participants with Ph-like ALL (US only) with TKI-targetable lesions involving any of the following kinase genes: ABL1, ABL2, cerebrospinal fluid (CSF1R), and platelet-derived growth factor receptor, beta polypeptide (PDGFRB).
  4. Participants with bone marrow relapse defined as: M2 marrow (5%-24% lymphoblasts) by morphology with confirmatory testing consisting of ≥5% lymphoblasts by flow cytometry or BCR-ABL1 fluorescence in situ hybridization (FISH) or ≥10^-2 leukemic clone identified by immunoglobulin heavy chain-T-cell receptor polymerase chain reaction (PCR) or M3 marrow (≥25% lymphoblasts) by morphology.
  5. Participants with combined bone marrow and extramedullary disease.
  6. Performance Status: Karnofsky performance status ≥50% for patients >16 years of age or Lansky Play Scale ≥50% for patients ≤16 years of age.
  7. Have recovered to less than Grade 2 National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) version 5, or to baseline, from any nonhematologic toxicities (except alopecia) due to previous therapy.
  8. Participants must meet the following criteria related to prior therapies:
  9. Cytoreduction with hydroxyurea: Hydroxyurea can be initiated and continued for up to 24 hours before the start of protocol therapy.
  10. Participants who relapsed while receiving cytotoxic therapy: At least 14 days must have passed since the completion of the last dose of chemotherapy before the first dose of ponatinib can be given except for the following: intrathecal (IT) chemotherapy and/or maintenance therapy such as vincristine, mercaptopurine, methotrexate, or glucocorticoids. There is no waiting period for those relapsing on maintenance-like therapy.
  11. 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.
  12. Hematopoietic growth factors: Before the first dose of ponatinib, at least 7 days must have passed since completion of therapy with granulocyte colony-stimulating factor or other growth factors, and at least 14 days must have passed since completion of therapy with pegfilgrastim.
  13. Biologics and Targeted Therapies: Before the first dose of ponatinib, at least 7 days must have passed since the last dose of a biologic agent. For agents that have known AEs occurring beyond 7 days after administration, this period must be extended beyond the time during which AEs are known to occur. The duration of this interval must be discussed with the sponsor's medical monitor/designee.
  14. Monoclonal antibodies: After the last dose of monoclonal antibody, at least 3 half-lives of the administered antibody must have passed before the first dose of ponatinib.
  15. Immunotherapy: Before the first dose of ponatinib, at least 30 days must have passed after the completion of any type of immunotherapy (eg, tumor vaccines, chimeric antigen receptor T-cell [CAR-T-cell]).
  16. Immunosuppressive therapy: Before the first dose of ponatinib, at least 14 days must have passed after the completion of immunosuppressive therapy (including regimens following stem cell transplant).
  17. Radiotherapy: No washout period is necessary for radiation given to any extramedullary site other than central nervous system (CNS); ≥90 days must have passed if participant received prior total body irradiation or craniospinal or cranial radiotherapy.
  18. Anthracyclines: Participants must have had a lifetime exposure of <400 mg/m2 of doxorubicin equivalents of anthracyclines.

  19. Adequate renal, hepatic, cardiac function with normal QT function, and with no evidence of pancreatitis.

You CAN'T join if...

  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. Isolated extramedullary disease.
  4. Diagnosis of ALL, MPAL, or Ph-like ALL (US only) with targetable kinase-activating lesions after treatment with cytotoxic therapy for another cancer.
  5. Diagnosis of another concurrent primary malignancy.
  6. Clinically significant cardiovascular disease, including but not limited to:
  7. Any history of myocardial infarction (MI) or unstable angina.
  8. History of or presence of heart block, and/or clinically significant ventricular or atrial arrhythmias.
  9. 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.
  10. 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).
  11. Uncontrolled hypertriglyceridemia (triglycerides ≥450 mg/dL). (Participants with triglycerides ≥ 450 mg/dL may be enrolled in the absence of any significant cardiovascular risk after discussion with the sponsor's medical monitor/designee.).
  12. Current systemic use of any medications or herbal supplements that are known to be strong inhibitors or strong inducers of CYP3A within 7 days before the first dose of study drug.
  13. . Planned non-protocol chemotherapy, radiation therapy, another investigational agent, or immunotherapy while participant is on study treatment.
  14. . Known gastrointestinal disease or gastrointestinal procedure that could interfere with the oral absorption of ponatinib.
  15. . Participants with DNA fragility syndromes, such as Fanconi anemia and Bloom syndrome.
  16. . Participants with Down syndrome. 16. Ongoing or active systemic infection, including but not limited to known seropositive HIV, or known active hepatitis B or C infection.
  17. . Participants with pre-existing significant CNS pathology including: history of severe brain injury, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination/movement disorder, or autoimmune disease with CNS involvement are not eligible. Participants with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible. (Participants with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved).
  18. . Uncontrolled seizure disorder. (Participants with seizure disorders that do not require antiepileptic drugs or are well controlled with stable doses of antiepileptic drugs are eligible).
  19. . History of severe coagulopathy or vascular events.


  • UCSF Medical Comprehensive Cancer not yet accepting patients
    San Francisco California 94143-3010 United States
  • Rady Childrens Hospital San Diego - PIN not yet accepting patients
    San Diego California 92123 United States
  • Children's Hospital Los Angeles not yet accepting patients
    Los Angeles California 90027 United States

Lead Scientist at UC Health

  • Mignon Loh (ucsf)
    Professor, Pediatrics. Authored (or co-authored) 232 research publications.


accepting new patients
Start Date
Completion Date
Phase 1/2
Study Type
Last Updated