MDACC Study Summary 2007-0879

Study Summary
No. 2007-0879:.......Leukemia......Hagop Kantarjian......Leukemia

Study Summary Title



Study Summary Number:	2007-0879

Study Title:	A Phase 1/2 Study of ARRY-520 in Patients with Advanced Myeloid Leukemia

Physician

New Patient Referral



Name:	Hagop Kantarjian	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:	713-792-7026 Contact us about clinical trials

General Information



Disease Group:	Leukemia	Supported By:	Array BioPharma Inc.

Phase of Study:	Phase I/Phase II	Return Visit:	Schedule 1: Up to 3 times weekly until CR or failure Schedule 2: Days 1, 4 and 7; and up to 3 times weekly until CR or failure.

Treatment Agents:	ARRY-520	Home Care:	NA

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

Estimated Length of Stay in Houston:	NA


Description/ Intervention:	The goal of this clinical research study is to test the safety of ARRY-520 and see what effects it has on patients with MDS. Pharmacodynamic (PD) testing will also be studied. PD testing measures where and how the study drug acts on the body.

Study Objectives / Outcomes

PHASE I
In patients with select myeloid leukemias and advanced myelodysplastic syndrome (MDS):

Primary

Determine sequentially the safety, tolerability, and MTD of ARRY-520 given in one of two schedules:
Schedule 1: IV over 1 hour on Day 1; only then, upon completion of Schedule 1:
Schedule 2: IV over 1 hour on Days 1, 3, and 5;
Evaluate the plasma PK profile of ARRY-520.

Secondary

Obtain a preliminary assessment of the biological activity of KSP inhibition in hematological tumor cells and through analysis of surrogate serum markers.
Assess preliminary antileukemic activity of ARRY-520 treatment.

PHASE I EXPANSION
In patients with advanced MDS:

Primary

Determine the safety of ARRY-520.

Secondary

Assess the preliminary activity of ARRY-520.

PHASE 2
In patients with acute myeloid leukemia (AML) and advanced MDS, with up to 2 prior treatment regimens:

Primary:

Determine the antileukemic activity of ARRY-520.

Secondary:

Evaluate the safety profile of ARRY-520

Study Status Information



Study Activation / Registration Date:	02/29/2008

IRB Review and Approval Date:	02/29/2008

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Open

Projected Accrual:	107

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) Phase I: Histologically or cytologically documented AML (incuding RAEB-t) or advanced MDS (RAEB), CMML, and CML-BP. Relapsed or refractory disease or confirmed new diagnosis in patients who are not eligible for, or refuse, recommended or standard of care treatment;

2) Phase 1 Expansion: Patients with Intermediate-2 or High risk MDS, who have failed one prior chemotherapy regimen which should have included a hypomethylating agent (azacitidine or decitabine). Prior lenalidomide and hydroxyurea are allowed;

3) Phase 2: Histologically or cytologically documented AML or advanced MDS. Relapsed or refractory disease, with up to 2 prior treatment regimens, or confirmed new diagnosis in patients who are not eligible for, or refuse, recommended or standard of care treatment;

4) Males and females of age >/= 17 years at the time of signing the informed consent;

5) Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;

6) In the absence of rapidly progressing disease, prior chemotherapy or immunotherapy must have been discontinued, at least two weeks (28 days for Mylotarg) prior to enrollment into the study and patients must have recovered from the toxic effects of prior therapy;

7) Major surgery must have been performed at least four weeks prior to enrollment in the study, and patients must have recovered from all related toxicities;

8) Adequate hepatic and renal function defined as follows: - Bilirubin of < 1.5 mg/dL; - Aspartate aminotransferase (AST)/Serum Glutamic Oxaloacetic Transaminase (SGOT) and/or alanine aminotransferase (ALT)/Serum Glutamic Pyruvic Transaminase (SGPT) </= 2.5 x ULN; - Serum creatinine </= 1.5 x ULN; - All qualifying laboratory parameters must be determined within seven days prior to first treatment;

9) Voluntarily sign an informed consent;

10) Women of child-bearing potential (WCBP), defined as a sexually mature woman who has not undergone a hysterectomy or who has not been naturally post-menopausal for at least 24 consecutive months, must have a negative serum or urine pregnancy test prior to initiation of treatment;

11) WCBP and all sexually active male subjects must agree to use adequate methods of birth control (per institutional guidelines) throughout the study.

Exclusion Criteria:

1) Concurrent cytotoxic therapy, or biological, endocrine and immunological response modifiers;

2) Use of an investigational agent that is not expected to be cleared by the first dosing of ARRY-520 or that has demonstrated to have late side effects. Patients should have recovered from the side effects to a Grade 0 or 1 (except alopecia);

3) Patients receiving concomitant radiation therapy, or previous radiation to > 25% of the bone marrow;

4) Other active malignancies (other than non-melanoma skin cancer, cervical intraepithelial neoplasia, or localized prostate cancer with a current prostate-specific antigen level of < 1.0 mg/dL);

5) Known Human Immunodeficiency Virus (HIV) positive;

6) Patients with CNS involvement as documented by spinal fluid cytology. Individuals with signs or symptoms of leukemic meningitis must have a lumbar puncture within two weeks prior to enrollment in the study. If blasts are present in the cerebrospinal fluid, the patient is not eligible to particpate in the study;

7) Active, uncontrolled infection requiring systemic antibiotic therapy or other serious underlying medical condition which would impair the ability of the patient to receive protocol treatment;

8) New York Heart Association (NYHA) class 2 or greater (for patients with symptomatic congestive heart failure only);

9) Dementia or altered mental status that would preclude understanding and rendering of informed consent.

Links

Registration Number: NCT00637052
Study Information on Clinical Trials Registry (clinicaltrials.gov)