MDACC Study Summary 2011-0333

Study Summary
No. 2011-0333:.......Leukemia......Jorge Cortes......Leukemia

Study Summary Title



Study Summary Number:	2011-0333

Study Title:	AN OPEN-LABEL, PHASE I/II STUDY OF TWO DIFFERENT SCHEDULES OF DASATINIB (SPRYCEL) AND DECITABINE (DACOGEN) USED IN COMBINATION FOR PATIENTS WITH ACCELERATED OR BLASTIC PHASE CHRONIC MYELOGENOUS LEUKEMIA (Protocol CA180357)

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:	BMS

Phase of Study:	Phase I/Phase II	Return Visit:

Treatment Agents:	Dasatinib Decitabine	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 combining Spyrcel
(dasatinib) and Dacogen (decitabine) can help to control CML. The dose level
of decitabine will also be studied.

Dasatinib is designed to block the protein that is responsible for chronic
myeloid leukemia.

Decitabine is designed to affect the mechanism that cells use to control the
expression of certain genes, some of which are important in the progression of
CML.

Study Objectives / Outcomes

Primary Objectives
a) For phase I: To define the maximally tolerated dose (up to the target dose) of the combination of dasatinib (Sprycel) and decitabine (5-aza-deoxycitidine; Dacogen) in patients with chronic myelogenous leukemia (CML) in the accelerated (AP) or blastic (BP) phases.

b) For phase II: To assess the efficacy, measured as the response to therapy during the first 3 months of therapy, of the combination of dasatinib and decitabine in patients with CML in AP or blastic BP phases.

Secondary Objectives
a) To determine the duration of response and survival with the combination of dasatinib and decitabine in advanced phase CML.

b) To establish the toxicity of the combination of dasatinib and decitabine therapy.

c) To determine the effects on gene methylation of decitabine given in combination with dasatinib.

Study Status Information



Study Activation / Registration Date:	06/12/2012

IRB Review and Approval Date:	06/12/2012

Study Type:	Phase Ii Or Phase I/Ii

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) Patients age 18 years of age or older with CML-AP, CML-BP or Philadelphia chromosome-positive acute myeloid leukemia defined as follows: CML-AP is defined by the presence of 15-29% blasts in peripheral blood (PB) or bone marrow (BM), >/= 20% basophils in PB or BM, >/= 30% blasts plus promyelocytes (with blasts <30%) in PB or BM, <100 x10(9)/L platelets unrelated to therapy, or by clonal cytogenetics evolution (i.e., the presence of cytogenetic abnormalities other than the Philadelphia chromosome); CML-BP is defined by the presence of >/= 30% blasts in the bone marrow and/or peripheral blood or the presence of extramedullary disease.

2) Patients are eligible whether they have received or not prior TKI therapy. For the phase I portion of the study, patients who had received prior therapy with dasatinib should have been able to tolerate the dose equivalent to the starting dose of dasatinib in the dose level at which the patient is being entered. Patients who previously received dasatinib but never at the dose being proposed are eligible provided they tolerated the maximum dose they were prescribed with no grade 3-4 toxicity not responding to optimal management.

3) ECOG performance status 0-3.

4) Men and women of childbearing potential should practice effective methods of contraception. Men and women of childbearing potential are defined as: a male that has not been surgically sterilized or a female that has not been amenorrheic for at least 12 consecutive months or that has not been surgically sterilized. Patients must use birth control during the study and for 3 months after the last dose of study drug if they are sexually active.

5) Women of childbearing potential must have a pregnancy test at screening.

6) Signed informed consent.

7) Patients must have been off all prior therapy for CML for 2 weeks prior to start of study therapy and recovered from the toxic effects of that therapy. Exceptions to these are hydroxyurea and TKIs (including but not limited to imatinib, nilotinib, and bosutinib) which should be discontinued >/= 24 hrs prior to the start of therapy. Patients who are receiving dasatinib prior to enrollment do not have to discontinue this agent prior to start of study therapy.

8) Adequate organ function: Serum creatinine </= 2.0 mg/dl or creatinine clearance >/=60 mL/min; Total bilirubin </= 1.5 x ULN (unless considered due to Gilbert's syndrome or hemolysis); Alanine aminotransferase (ALT) </= 3 x ULN unless considered due to leukemic involvement.

Exclusion Criteria:

1) NYHA cardiac class 3-4 heart disease.

2) Cardiac disease including: Uncontrolled angina within 3 months. Diagnosed or suspected congenital long QT syndrome; Any history of clinically significant ventricular arrhythmias (eg, 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; Uncontrolled hypertension (defined for this protocol as sustained systolic BP >/=150 and diastolic >/=100); Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes.

3) Serious uncontrolled medical disorder or uncontrolled active systemic infection or current unstable or decompensated respiratory or cardiac conditions which makes it undesirable or unsafe for the patient to participate in the study.

4) Patients with known, clinically significant pericardial or pleural effusion.

5) History of significant bleeding disorder unrelated to cancer, including diagnosed congenital bleeding disorders (e.g., von Willebrand's disease), or diagnosed acquired bleeding disorders within one year (e.g., acquired anti-factor VIII antibodies).

6) Subject is receiving potent inhibitors of CYP3A4; for such medications, a wash-out period of >/= 7 days is required prior to starting dasatinib unless discontinuation or substitution of such an inhibitor is not in the best interest of the patient as determined by the investigator. These include the following medications: itraconazole, ketoconazole, miconazole, voriconazole; amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir; ciprofloxacin, clarithromycin, diclofenac, doxycycline, enoxacin, isoniazid, ketamine, nefazodone, nicardipine, propofol, quinidine, telithromycin. In instances where use of these agents is felt to be required for the best management of the patients, inclusion of such a patients should be discussed with PI and the rationale documented.

7) Females who are pregnant or are currently breastfeeding.

8) Patients that are eligible (including having available donor) and willing to receive an allogeneic stem cell transplant within 4 weeks.

Links

Registration Number: NCT01498445
Study Information on Clinical Trials Registry (clinicaltrials.gov)