MDACC Study Summary 2007-0939

Study Summary
No. 2007-0939:.......Leukemia......Jorge Cortes......Leukemia

Study Summary Title



Study Summary Number:	2007-0939

Study Title:	A Phase I Study of PHA-739358 in Adult Patients with Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Resistant or Intolerant to Imatinib and/or other 2nd Generation c-ABL Therapy

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:	Nerviano Medical Sciences

Phase of Study:	Phase I	Return Visit:	Weekly for the first month, then every month.

Treatment Agents:	PHA-739358	Home Care:	All treatment is to be given at MDACC.

Treatment Loc:	Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions

Estimated Length of Stay in Houston:	None anticipated. However, will admit to hematology service beds if inpatient hospitalization is required.


Description/ Intervention:	The goal of this clinical research study is to learn the highest tolerable dose of PHA-739358 that can be given to patients with CML or Ph+ALL in which the disease has not responded to certain other forms of treatment. The safety of this drug will also be studied.

Study Objectives / Outcomes

Primary Objectives
• To determine the maximum tolerated dose (MTD) and the Dose Limiting Toxicities (DLTs) during the first cycle of treatment with PHA-739358 administered as 3-h IV infusion daily for 7 consecutive days (Days 1 to 7) of a 14-day cycle (Schedule A) in adult patients with advanced Chronic Myeloid Leukemia (Accelerated/Blastic phase CML) or Philadelphia-Chromosome positive Acute Lymphoblastic Leukemia Ph+
ALL), resistant or intolerant to imatinib and/or other 2nd-generation c-ABL therapy

• To determine the maximum tolerated dose (MTD) and the Dose Limiting Toxicities (DLTs) during the first cycle of treatment with PHA-739358 administered as 3-h IV infusion daily for 14 consecutive days of a 21-day cycle (Schedule B) in adult patients with advanced Chronic Myeloid Leukemia (Accelerated/Blastic phase CML) or Philadelphia- Chromosome positive Acute Lymphoblastic Leukemia (Ph+ ALL), resistant or intolerant to imatinib and/or other 2nd-generation c-ABL therapy.

Secondary Objectives
• To define the safety profile of PHA-739358 for each of the two different schedules of
treatment.

• To assess the pharmacokinetics of PHA-739358 in plasma for each of the two different
schedules of treatment

• To explore the relationship between PHA-739358 levels in plasma and the modulation of
biologic targets for each of the two different schedules of treatment

• To document any evidence of activity for each of the two different schedules of
treatment, including the subset of patients with T315I mutant leukemias when
applicable.

Study Status Information



Study Activation / Registration Date:	06/03/2008

IRB Review and Approval Date:	02/14/2008

Study Type:	Phase I

Recruitment Status:	Open

Projected Accrual:	50

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) Age >/= 18 years.

2) Personally signed and dated informed consent indicating that the patient is aware of the neoplastic nature of his/her disease and has been informed of the procedures to be follwed, the experimental nature of the therapy, alternatives, potential benefits, sie effects, risks and discomforts.

3) Confirmed diagnosis of Chronic Myeloid Leukemia (Accelerated/Blastic Phase), or Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia, resistant or intolerant to imatinib and/or one 2nd generation ABL-kinase inhibitor therapy.

4) Eastern Cooperative Oncology Group (ECOG) performance status </=2.

5) Normal blood pressure (</- 140/90 mmHg) with or without anti-hypertensive treatment for at least one week.

6) Adequate hepatic and renal function, as defined by: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) not higher tan 2.5 x the upper normal limit or not higher than 5 x the upper normal limit in cases of suspected liver involvement. Serum total bilirubin levels not higher than 1.5 x the upper normal limit. Serum creatinine levels not higher than 1.5 x the upper normal limit.

7) Prior conventional chemo-immunotherapy must have been completed 2 weeks before study treatment start with the following exceptions: cytoreductive therapy (leukapheresis and/or hydroxyurea and/or steroids and/or anagrelide) will be allowed to control peripheral WBC or platelets counts up to 24 hours prior to first administration of the study drug; imatinib mesylate/dasatinib/nilotinib/other tyrosine kinase inhibitors (1 week before), and hematopoietic stem cell transplantation (6 weeks before);

8) **continued from above: for any other investigational drug a total of 5 half-lives is a standard minimum wash out period that is recommended before study treatment starts, provided toxicities have resolved to grade </= 1.

9) All acute toxic effects (excluding alopecia and residual Grade 1 neurotoxicity) of any prior therapy must have resolved to NCI CTCAE version 3.0 Grade </= 1.

10) A negative pregnancy test (if female in reproductive years).

Exclusion Criteria:

1) Major surgeries within 4 weeks from study treatment start or not fully recovered from any previous surgical procedure (except surgery related to diagnostic procedures).

2) Presence of active central nervous system (CNS) leukemia.

3) Active uncontrolled infection.

4) Known history of human immunodeficiency virus (HIV) infection.

5) Grade 3 or 4 bleeding, unrelated to CML or ALL.

6) Abnormal LVEF (< 40% by TTE performed within the last 2 weeks).

7) Significant cardiovascular disease (i.e., uncontrolled arrhythias, unstable angina), or a major thromboembolic event (myocardial infarction, stroke, transient ischemic attack, pulmonary embolism, or non-catheter-related deep-vein thrombosis) in the last 6 months.

8) Pregnancy or breast-feeding. Female patients must agree to use effective contraception, be surgically sterile or be postmenopausal. Male patients must agree to use effective contraception and have no intention to father a child for three months after the end of treatment, or be surgically sterile. The definition of effective contraception will be based on the judgment of the principal Investigator or a designated associate.

9) Presence of any medical/psychiatric condition or laboratory abnormalities which may limit full compliance with the study, increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study.

10) Current enrollment in another clinical trial with other investigational agents.

11) Patients with a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds).

12) Patients presenting risk factors for torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).

13) Use of concomitant medications that may prolong the QT/QTc interval. A wash out of 5 half lives should elapse prior to treatment start to be eligible.

Links

Registration Number: Not Registered