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Ponatinib - Frontline for Chronic Myeloid Leukemia (CML) in Chronic Phase (CP)
This study is not yet open for participant recruitment.
Verified April 2012 by M.D. Anderson Cancer Center
First Received on April 2, 2012. No Changes Posted
|M.D. Anderson Cancer Center |
Information provided by (Responsible Party):
|M.D. Anderson Cancer Center|
The goal of this clinical research study is to learn if ponatinib can help to control chronic myeloid leukemia (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 leukemia in certain cells.
|Study Type: ||Interventional |
|Study Design: ||Endpoint Classification: Safety/Efficacy Study|
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title: ||Ponatinib as Initial Therapy for Patients With Chronic Myeloid Leukemia in Chronic Phase|
Resource links provided by NLM:
MedlinePlus related topics: Cancer Chronic Myeloid Leukemia Leukemia
U.S. FDA Resources
Further study details as provided by M.D. Anderson Cancer Center:
Primary Outcome Measures: Complete Cytogenetic Response (CCyR) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
The binary indicator of complete cytogenetic remission measured from start of therapy to 6 months, denoted by CCR6. Method of Kaplan and Meier21 used to estimate the unadjusted distributions of time to toxicity, duration of CCR, and the times to transformation to accelerated phase or blastic phase chronic myeloid leukemia (CML).
Secondary Outcome Measures: Time to Toxicity [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
Time to toxicity (T) defined as any grade 3 or 4 drug-related non-hematologic adverse event that has not resolved to grade 2 or less after 6 weeks of optimal therapeutic management, or drug-related toxicity of any grade that in the opinion of the investigator prevents further therapy with ponatinib. Secondary outcomes include duration of complete cytogenic response (CCR), time to transformation to accelerated phase or blastic phase chronic myeloid leukemia (CML), and major molecular response (MMR). Time to toxicity monitored using the Bayesian method of Thall, et al.
|Estimated Enrollment: ||50|
|Study Start Date: ||September 2012|
|Estimated Primary Completion Date: ||September 2016 (Final data collection date for primary outcome measure)|
Arms Assigned Interventions
|Experimental: Ponatinib |
Patients receive ponatinib at a dose of 45 mg orally, once daily. If a dose is missed or vomited, the next dose should not be increased to account for missing a dose. Total duration of therapy 3 to 5 years.
|Drug: Ponatinib |
Starting dose: 45 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 should not eat within 2 hours before or after taking the drug. 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. Bring this diary to every study visit, as described below.
The tests and procedures for this study have a wide range of time in which they can be done. In general, your schedule of study visits will be as follows:
Weekly in Month 1 Monthly in Year 1 Three (3) to 4 times in Year 2 Two (2) to 3 times in every year after that The study staff will help you schedule your study visits. The following tests and procedures will be performed:
Every 1-2 weeks for the first 4 weeks, then every 4-6 weeks for the first year, then every 3-4 months for the next year, then every 4-6 months after that, blood (about 1/2 tablespoon) will be drawn for routine tests. Every 3 months for the first year, you will have an ECG. Every 3 months for the first year, then every 6-12 months after that, you will have a physical exam. Every 3-4 months for the first year, then every 6-12 months after that, blood (about 2 teaspoons) will be drawn to measure levels of leukemia cells in your body. 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, you will have a bone marrow aspirate for genetic testing and to check the status of the disease. Length of Participation:
You may continue taking 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.
If you leave the study, you will be called or you will come to the clinic within 30 days 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 not FDA approved or commercially available. It is currently being used for research purposes only.
Up to 50 patients will take part in this study. All will be enrolled at MD Anderson.
|Ages Eligible for Study: ||18 Years and older|
|Genders Eligible for Study: ||Both|
|Accepts Healthy Volunteers: ||No|
Diagnosis of Ph-positive (by cytogenetics or FISH) or Bcr-ABL-positive (by PCR) CML in early chronic phase CML (i.e., time from diagnosis </= 6 months). Except for hydroxyurea, patients must have received no or minimal prior therapy, defined as </=1 month of prior IFN- (with or without ara-C) and/or an FDA-approved tyrosine kinase inhibitor (e.g, dasatinib, nilotinib). Age >/=18 years Eastern Cooperative Oncology Group (ECOG) performance of 0-2. Adequate end organ function, defined as the following: total bilirubin <1.5 * ULN, SGPT <2.5 * upper limit of normal (ULN),creatinine clearance (CrCl) >/= 30 mL/min at screening (calculation according to Cockroft & Gault formula). Patients must sign an informed consent indicating they are aware of the investigational nature of this study, in keeping with the policies of the hospital. Women of pregnancy potential must practice an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control. Adequate forms of contraception are barrier methods (e.g., condoms, diaphragm), oral, depo provera, or injectable contraceptives, intrauterine devices, spermicidal jelly or foam, abstinence, and tubal ligation. Women and men must continue birth control for the duration of the trial & at least 3 months after the last dose of study drug. **continued from above: All WOCBP MUST have a negative serum or urine pregnancy test within 7 days prior to first receiving investigational product. If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study. Exclusion Criteria:
New York Heart Association (NYHA) cardiac class 3-4 heart disease Cardiac Symptoms: Patients meeting the following criteria are not eligible: Unstable angina or myocardial infarction within 3 months; Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes); Prolonged QTc interval on pre-entry electrocardiogram (> 470 msec) on both the Fridericia and Bazett's correction; Symptomatic congestive heart failure within 3 months prior to first dose of ponatinib (NYHA class III or IV). Patients with active, uncontrolled psychiatric disorders including: psychosis, major depression, and bipolar disorders. Pregnant or breast-feeding women are excluded. Patients with history of pancreatitis. Patients in late chronic phase (i.e., time from diagnosis to treatment >6 months), or blast phase are excluded. The definitions of CML phases are as follows: A. Early chronic phase: time from diagnosis to therapy </= 6 months; B. Late chronic phase: time from diagnosis to therapy > 6 months; C. Blastic phase: presence of 30% blasts or more in the peripheral blood or bone marrow; D. 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 * 10(9)/L unrelated to therapy; Documented extramedullary blastic disease outside liver or spleen. **continued from above: E. 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. However, patients with clonal evolution as the only criterion of accelerated phase have a significantly better prognosis, and when present at diagnosis may not impact the prognosis at all. Thus, patients with clonal evolution and no other criteria for accelerated phase will be eligible for this study.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01570868
|Contact: Jorge Cortes, MD ||713-794-5783 |
|UT MD Anderson Cancer Center |
|Houston, Texas, United States, 77030 |
Sponsors and Collaborators
M.D. Anderson Cancer Center
|Principal Investigator: ||Jorge Cortes, MD ||UT MD Anderson Cancer Center|
UT MD Anderson Cancer Center Website
No publications provided
|Responsible Party: ||M.D. Anderson Cancer Center|
|ClinicalTrials.gov Identifier: || NCT01570868 History of Changes |
|Other Study ID Numbers: ||2012-0074|
|Study First Received: ||April 2, 2012|
|Last Updated: ||April 2, 2012|
|Health Authority: ||United States: Food and Drug Administration|
Keywords provided by M.D. Anderson Cancer Center:
Chronic Myeloid Leukemia
Major molecular response
Complete molecular response
Additional relevant MeSH terms:
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Bone Marrow Diseases
ClinicalTrials.gov processed this record on April 03, 2012