MDACC Study Summary 2005-0422

Study Summary
No. 2005-0422:.......Leukemia......Jorge Cortes......Leukemia

Study Summary Title



Study Summary Number:	2005-0422

Study Title:	Therapy of Early Chronic Phase Chronic Myelogenous Leukemia (CML) with Dasatinib (BMS-354825)

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:	N/A

Phase of Study:	Phase II	Return Visit:	Every 3-4 months for 1 year, then every 6-12 months.

Treatment Agents:	BMS-354825	Home Care:	Medication is self-administered (orally)

Treatment Loc:	Only at MDACC

Estimated Length of Stay in Houston:	None anticipated


Description/ Intervention:	The goal of this clinical research study is to learn if BMS-354825 (dasatinib) can help to control CML in chronic phase. The safety of this drug will also be studied.

Study Objectives / Outcomes

Primary:
· To estimate the proportion of patients with previously-untreated chronic phase CML attaining major molecular response by 12 months of treatment with dasatinib.

Secondary:
· To estimate the proportion of patients with Ph-positive early chronic phase CML achieving a complete cytogenetic response after dasatinib therapy.
· To evaluate the durations of hematologic, cytogenetic and molecular response to dasatinib.
· To define the time to progression and overall survival for patients with CML in early chronic phase treated with dasatinib.
· To evaluate the toxicity profile of dasatinib 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 dasatinib.
· To analyze differences in response rates and in prognosis within different risk groups and patient characteristics.

To assess correlation between trough concentration and pleural effusion.
To assess the inhibition of platelet function and assess correlation between drug concentration and degree of platelet inhibition.
To assess the effect of dasatinib therapy in bone metabolism as determined by changes in serum alkaline phosphatase (bone specific isoenzyme) and trabecular bone volume.
To evaluate symptom burden in patients with CML receiving dasatinib

Exploratory Objective:

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

Study Status Information



Study Activation / Registration Date:	11/08/2005

IRB Review and Approval Date:	07/06/2005

Study Type:	Therapeutic

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 or Bcr-Abl positive CML in early chronic phase CML (i.e., time from diagnosis </= 12 months). Except for hydroxyurea, patients must have received no or minimal prior therapy, defined as <1 month of prior IFN-alpha (with or without ara-C) and/or imatinib

2) Continued from above #1: 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

3) Age >/= 16 years (Age >18 years to participate in optional symptom burden assessment)

4) ECOG performance of 0-2

5) Adequate end organ function, defined as the following: total bilirubin <1.5 x ULN, SGPT <2.5x ULN, creatinine <1.5x ULN

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) Reliable telephone access to receive calls from an interactive voice response system (IVR) (only applicable to patients who will participate in optional symptom burden assessment)

Exclusion Criteria:

1) New York Heart Association (NYHA) cardiac class 3-4 heart disease

2) Cardiac Symptoms: Patients meeting the following criteria are not eligible unless cleared by Cardiology: Uncontrolled angina within 3 months; Diagnosed or suspected congenital long QT syndrome; Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes); Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec) on both the Fridericia and Bazett's correction; Uncontrolled hypertension; History of significant bleeding disorder unrelated to cancer, including:

3) Cont: Diagnosed congenital bleeding disorders (von Willebrand's disease) Diagnosed acquired bleeding disorder w/in 1 year (acquired anti-factor VIII antibodies);Pts currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes including: quinidine, procainamide, disopyramide amiodarone, sotalol, ibutilide, dofetilide erythromycins, clarithromycin chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.

4) Patients with active, uncontrolled psychiatric disorders including: psychosis, major depression, and bipolar disorders

5) 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.

6) Continued: Women must continue birth control for the duration of the trial and at least 3 months after the last dose of study drug; Pregnant or breast-feeding women are excluded; All WOCBP MUST have a negative pregnancy test 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.

7) Patients in late chronic phase (i.e., time from diagnosis to treatment >12 months), accelerated or blast phase are excluded.

8) The definitions of CML phases are as follows: a) Early chronic phase: time from diagnosis to therapy </= 12 months; Late chronic phase: time from diagnosis to therapy > 12 months, b) Blastic phase: presence of 30% blasts or more in the peripheral blood or bone marrow, c) 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

Links

Registration Number: NCT00254423
Study Information on Clinical Trials Registry (clinicaltrials.gov)