Ponatinib - 2nd Line Therapy
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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Ponatinib as Second Line Therapy for Patients With Chronic Myeloid Leukemia in Chronic Phase Resistant or Intolerant to Imatinib|
- Major cytogenetic response (MCyR) With Second Line Ponatinib Therapy [ Time Frame: At 6 months from start of therapy ] [ Designated as safety issue: No ]Complete Hematologic Remission (CHR) - normalization >/= 4 weeks bone marrow (<5% blasts) and peripheral blood with WBC <10 x 10^9/L and no peripheral blasts, promyelocytes or myelocytes; disappearance all signs/symptoms of disease. further classified by suppression of Philadelphia chromosome (Ph) by cytogenetics: No cytogenetic response - Ph positive >95% of pretreatment value; Minor cytogenetic response - Ph positive 36-95% of pretreatment value; Partial cytogenetic response - Ph positive 1-35% of pretreatment value; Complete cytogenetic response - Ph positive 0%. Partial Hematologic Response (PHR) - CHR except for persistence of immature cells (myelocytes, metamyelocytes), or splenomegaly <50% pretreatment, or thrombocytosis >450x10^9/L but <50% of pretreatment. Major cytogenetic response = complete + partial (Ph positive <35%).
- Time to Toxicity [ Time Frame: Baseline to end of study, up to 4 years ] [ Designated as safety issue: Yes ]Toxicity defined as any grade 3 or 4 drug-related adverse event that is not responsive to standard therapeutic management and requires permanent treatment discontinuation. Time-to-toxicity monitored using the Bayesian method of Thall, et al. Kaplan and Meier. Evaluation of toxicity (clinic visit or telephone interview) every 3 months for the first year then every 6 to 12 months.
|Study Start Date:||January 2013|
|Estimated Primary Completion Date:||January 2019 (Final data collection date for primary outcome measure)|
Starting dose of Ponatinib: 30 mg by mouth once daily.
Starting dose of Ponatinib: 30 mg by mouth once daily.
Other Name: AP24534
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.
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01746836
|United States, Texas|
|University of Texas MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Jorge Cortes, MD||M.D. Anderson Cancer Center|