This trial is active, not recruiting.

Condition leukemia
Treatment ponatinib
Phase phase 2
Sponsor M.D. Anderson Cancer Center
Collaborator Ariad Pharmaceuticals
Start date January 2013
End date January 2019
Trial size 50 participants
Trial identifier NCT01746836, 2012-0669, NCI-2014-01911


The goal of this clinical research study is to learn if ponatinib can help to control CML in chronic phase. The safety of this drug will also be studied.

Ponatinib is designed to block the function of BCR-ABL, which is the abnormal protein responsible for causing CML. This may cause the cancer cells to die.

Ponatinib may cause a blood clot to form in an artery or in a vein. Depending on the location of the clot, this could cause a heart attack, a stroke, severe damage to other tissue, or death. A blood clot may occur within 2 weeks after you start taking the drug. About 25% (1 in 4) of patients taking the drug form an abnormal clot. Blood clots can occur in patients that do not have other known risk factors for forming clots. If you develop a blood clot, you will need to stop taking ponatinib. In some cases, emergency surgery could be needed to remove the clot and restore blood flow.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Starting dose of Ponatinib: 30 mg by mouth once daily.
ponatinib AP24534
Starting dose of Ponatinib: 30 mg by mouth once daily.

Primary Outcomes

Major cytogenetic response (MCyR) With Second Line Ponatinib Therapy
time frame: At 6 months from start of therapy
Time to Toxicity
time frame: Baseline to end of study, up to 4 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. Diagnosis of Ph-positive (by cytogenetics or FISH) or BCR-ABL-positive (by PCR) CML in chronic phase. 2. Patients should have demonstrated to have failure to therapy to one FDA-approved TKI (currently imatinib, dasatinib, and nilotinib are approved as frontline therapy), defined as per European leukemiaNet (ELN) recommendations: 1. Less than complete hematologic response (CHR) at or beyond 3 months; 2. No cytogenetic response at or beyond 6 months; 3. Less than PCyR (Ph+ >35%) at or beyond 12 months; 4. Less than CCyR at or beyond 18 months; 5. Loss of response or development of mutations or other clonal chromosomal abnormalities at any time during TKI treatment; 6. Intolerance to imatinib, dasatinib or nilotinib defined as grade 3 or 4 toxicity, or persistent grade 2 toxicity despite optimal management including dose adjustment, or in a patient where dose reductions are considered to be not in the patients best interest to obtain or maintain an adequate response. Intolerant patients should not have achieved or have lost major cytogenetic response at the time of enrollment. 3. Age >/= 18 years. 4. ECOG performance of 0-2. 5. Adequate end organ function, defined as the following: total bilirubin 470 msec) on both the Fridericia and Bazett's correction; Congestive heart failure (NYHA Class III or IV) within 3 months prior to first dose of ponatinib. 4. Patients with active, uncontrolled psychiatric disorders including: psychosis, major depression, and bipolar disorders. 5. Patients with uncontrolled hypertension (defined as sustained systolic blood pressure > 160 mmHg or diastolic > 100 mmHg). 6. Pregnant or breast-feeding women are excluded. 7. Patients with history of pancreatitis. 8. Patients in accelerated or blast phase, or patients who have ever been documented to be in blast phase CML, are excluded. The definitions of excluded CML phases are as follows: a. Blastic phase: presence of 30% blasts or more in the peripheral blood or bone marrow; b. Accelerated phase CML: presence of any of the following features: Peripheral or marrow blasts 15% or more; Peripheral or marrow basophils 20% or more; Thrombocytopenia < 100 x 10(9)/L unrelated to therapy; Documented extramedullary blastic disease outside liver or spleen; c. Clonal evolution defined as the presence of additional chromosomal abnormalities other than the Ph chromosome has been historically been included as a criterion for accelerated phase. 9. **continued from above: However, patients with clonal evolution as the only criterion of accelerated phase have a significantly better prognosis. Thus, patients with clonal evolution and no other criteria for accelerated phase will be eligible for this study, but analyzed separately. 10. Patients who have received more than one FDA-approved TKI for CML, or any investigational, non-FDA approved TKI.

Additional Information

Official title Ponatinib as Second Line Therapy for Patients With Chronic Myeloid Leukemia in Chronic Phase Resistant or Intolerant to Imatinib, Dasatinib or Nilotinib
Principal investigator Jorge Cortes, MD
Description Study Drug Administration: You will take ponatinib by mouth 1 time every day while you are on study with about a cup (8 ounces) of water. You may take ponatinib with or without food. If you vomit a dose, you should not take ponatinib again to make up for that dose. You should wait until your next scheduled dose. You will complete a study diary in which you will record the date and time that you take the study drug each time. If you miss any doses, you will also note this in the study diary. You will bring this diary to every study visit. Study Visits: The study staff will help you schedule your study visits. The following tests and procedures will be performed: - Blood (about 1/2 tablespoon each time) will be drawn for routine tests every 1-2 weeks for the first 4 weeks, every 4-6 weeks for the first year, every 3-4 months for second year, then every 4-6 months after that. These tests can be done by your home doctor and sent to your study doctor. - You will have an EKG every 3 months for the first year. - You will have a physical exam and you will be asked about any drugs you may be taking and any side effects you may be having every 3 months for the first year, then every 6-12 months after that. - Blood (about 2 teaspoons) will be drawn to check the status of the disease every 3-4 months for the first year, then every 6-12 after that. - You will have a bone marrow aspirate for genetic testing and to check the status of the disease every 3-4 months for the first year, then every 6-12 months for the next 2 years, then every 2-3 years after that. Length of Study: You may take the study drug for up to 5 years. You will be taken off study early if intolerable side effects occur, if the disease gets worse, or if you are unable to follow study directions. Your participation on the study will be over when you have completed the follow-up visit/call (described below). If the disease gets worse or the disease never responds to treatment with ponatinib, blood (about 1 tablespoon) will be drawn about 30 days after your last dose of ponatinib to check for changes in the BCR-ABL protein which may explain why there was no response to the study drug. Follow-Up: Within 30 days after you leave the study, you will be called or you will come to the clinic to learn about any side effects or symptoms you may be having. If you are called, this call will last about 2-3 minutes. This is an investigational study. Ponatinib is FDA approved to treat patients with certain types of leukemia. Its use in this study is investigational. Up to 50 participants will be enrolled in this study. All will be enrolled at MD Anderson.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by M.D. Anderson Cancer Center.