MDACC Study Summary 2012-0074

Study Summary
No. 2012-0074:.......Leukemia......Jorge Cortes......Leukemia

Study Summary Title



Study Summary Number:	2012-0074

Study Title:	Ponatinib as Initial Therapy for Patients with Chronic Myeloid Leukemia in Chronic Phase

Physician

New Patient Referral



Name:	Jorge Cortes	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Leukemia	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-794-5783 Contact us about clinical trials

General Information



Disease Group:	Leukemia	Supported By:	Ariad Pharmaceuticals, Inc.

Phase of Study:	Phase II	Return Visit:

Treatment Agents:	Ponatinib	Home Care:

Treatment Loc:	Only at MDACC

Estimated Length of Stay in Houston:


Description/ Intervention:	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 leukemia in certain cells.

Study Objectives / Outcomes

Primary:

To estimate the proportion of patients with previously-untreated chronic phase CML attaining complete cytogenetic response (CCyR) at 6 months of treatment with ponatinib.

Secondary:

To estimate the proportion of patients achieving a CCyR, major molecular response (MMR) and complete molecular response (CMR) at 3, 6, 12, 18 and 24 months of treatment with ponatinib

To estimate the time to CCyR, MMR and CMR for patients treated with ponatinib as initial therapy for CML
To evaluate the durations of hematologic, cytogenetic and molecular response to ponatinib.
To define the time to progression and overall survival for patients with CML in early chronic phase treated with ponatinib.

To evaluate the toxicity profile of ponatinib in patients with CML in early chronic phase.

To evaluate the probability of developing ABL mutations for patients with CML in early chronic phase treated with ponatinib.

To analyze differences in response rates and in prognosis within different risk groups and patient characteristics.

To investigate mechanisms of resistance in patients who develop resistance to ponatinib used as initial therapy for CML.

To evaluate symptom burden in patients with CML receiving ponatinib

Exploratory Objective:

To investigate the plasma/serum levels of specific miRNAs in CML patients receiving ponatinib as initial therapy for CML in CP.

Study Status Information



Study Activation / Registration Date:	04/27/2012

IRB Review and Approval Date:	04/27/2012

Study Type:	Phase I

Recruitment Status:	Open

Projected Accrual:	N/A

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

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 </= 6 months).

2) Patients must have received no or minimal prior therapy, defined as </=1 month of 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 </= 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 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.

Links

Registration Number: NCT01570868
Study Information on Clinical Trials Registry (clinicaltrials.gov)