Clinical trial NCT00637052: A Study of ARRY-520 in Patients With Advanced Myeloid Leukemia
Official title: A Phase 1/2 Study of ARRY-520 in Patients With Advanced Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Advanced MDS
Acute Myeloid Leukemia
Keywords: preleukemia
dysplasia of myeloid blood cells
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2008-03-17
Enrollment: 36
Sex: ALL
Minimum age (years): 17
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a 2-phase study during which patients with select myeloid leukemias or advanced myelodysplastic syndrome (MDS), who have failed, refused or are not eligible for standard treatment, will receive investigational study drug ARRY-520.

The study has 3 parts. The first phase of the study, Phase 1, has 2 parts. In the first part of Phase 1, patients with select myeloid leukemias or advanced MDS will receive increasing doses of study drug on different schedules in order to achieve the highest dose possible that will not cause unacceptable side effects. Approximately 30 patients (per schedule) from the US will be enrolled in Part 1 (Completed). In the second part of Phase 1, patients with advanced MDS will receive the best dose of study drug and schedule determined from the first part of the study. Approximately 10 patients from the US will be enrolled in Part 2 (Completed).

In the third part of the study, Phase 2, patients with acute myeloid leukemia (AML) or advanced MDS will receive the best dose of study drug and schedule determined from the first part of the study and will be followed to see what side effects the study drug causes and to see what effectiveness it has, if any, in treating the cancer. Approximately 40 patients from the US will be enrolled in Part 3 (Withdrawn).


Eligibility criteria: Key Inclusion Criteria (Part 2):

* Patients with either Intermediate-2 or High risk MDS or with AML (\>20% bone marrow blasts) with stable low or normal white blood cell count (WBC). Patients should have failed one prior chemotherapy regimen which should have included a hypomethylating agent.
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2.
* Discontinuation of prior treatment at least 2 weeks prior to the start of the study.
* Adequate hepatic and renal function.
* Additional criteria exist.

Key Exclusion Criteria (Part 2):

* Concurrent cytotoxic therapy, or biological, endocrine and immunological response modifiers.
* Previous radiation to \>25% of bone marrow.
* Other active malignancies.
* Known positive serology for the human immunodeficiency virus (HIV).
* Central nervous system involvement as documented by spinal fluid cytology.
* Active, uncontrolled infection.
* Additional criteria exist

Primary outcomes:
measure: Establish the maximum tolerated dose (MTD) of the study drug.
timeFrame: Part 1
measure: Characterize the pharmacokinetics (PK) of the study drug.
timeFrame: Part 1
measure: Characterize the safety profile of the study drug in terms of adverse events, dose limiting toxicity, clinical laboratory tests, weight, electrocardiograms and physical examinations.
timeFrame: Part 1 and Part 2
measure: Assess the efficacy of the study drug in terms of incidence of complete remission (CR) and hematologic improvement (CRp).
timeFrame: Part 3
Secondary outcomes:
measure: Assess the efficacy of the study drug in terms of incidence of CR and CRp.
timeFrame: Part 1 and Part 2
measure: Characterize the safety profile of the study drug in terms of adverse events, dose limiting toxicity, clinical laboratory tests, weight, electrocardiograms and physical examinations.
timeFrame: Part 3
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University School of Medicine, Winship Cancer Center
state: Georgia
city: Houston
country: United States
facility: University of Texas, M.D. Anderson Cancer Center
state: Texas
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Khoury HJ, Garcia-Manero G, Borthakur G, Kadia T, Foudray MC, Arellano M, Langston A, Bethelmie-Bryan B, Rush S, Litwiler K, Karan S, Simmons H, Marcus AI, Ptaszynski M, Kantarjian H. A phase 1 dose-escalation study of ARRY-520, a kinesin spindle protein inhibitor, in patients with advanced myeloid leukemias. Cancer. 2012 Jul 15;118(14):3556-64. doi: 10.1002/cncr.26664. Epub 2011 Dec 2.