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Ponatinib as Initial Therapy for Patients With Chronic Myeloid Leukemia in Chronic Phase

Phase 2
18 Years
Open (Enrolling)

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Trial Information

Ponatinib as Initial Therapy for Patients With Chronic Myeloid Leukemia in Chronic Phase

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.

Study Visits:

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


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 FDA approved to treat patients with certain
types of leukemia. Its use in this study is investigational.

Up to 50 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. 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
2. Patients must have received no or minimal prior therapy, defined as prior IFN-α (with or without ara-C) and/or an FDA-approved tyrosine kinase inhibitor
(e.g, dasatinib, nilotinib). Prior use of hydroxyurea or anagrelide is allowed with
no limitations.

3. Age >/=18 years

4. ECOG performance of 0-2.

5. Adequate end organ function, defined as the following: total bilirubin <1.5x ULN,
SGPT <2.5x ULN,creatinine clearance (CrCl) >/= 30 mL/min at screening (calculation
according to Cockroft & Gault formula).

6. 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.

7. 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.

8. **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:

1. NYHA cardiac class 3-4 heart disease

2. 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).

3. Patients with active, uncontrolled psychiatric disorders including: psychosis, major
depression, and bipolar disorders.

4. Pregnant or breast-feeding women are excluded.

5. Patients with history of pancreatitis.

6. 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 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 x 10(9)/L unrelated to therapy;
Documented extramedullary blastic disease outside liver or spleen.

7. **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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete Cytogenetic Response (CCyR)

Outcome Description:

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).

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Jorge Cortes, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

April 2012

Completion Date:

Related Keywords:

  • Leukemia
  • Leukemia
  • Chronic Myeloid Leukemia
  • CML
  • Chronic Phase
  • Cytogenetic response
  • CCyR
  • Major molecular response
  • MMR
  • Complete molecular response
  • CMR
  • Ponatinib
  • AP24534
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive



UT MD Anderson Cancer Center Houston, Texas  77030