A Phase I Study of Obatoclax (Pan Anti-Apoptotic BCL-2 Family Small Molecule Inhibitor), in Combination With Vincristine/Doxorubicin/Dexrazoxane, in Children With Relapsed/Refractory Solid Tumors or Leukemia
I. Estimate the maximum-tolerated dose and/or recommended phase II dose of obatoclax
mesylate in combination with vincristine sulfate, doxorubicin hydrochloride, and dexrazoxane
hydrochloride in pediatric patients with refractory solid tumors.
II. Define and describe the toxicities of obatoclax mesylate in these patients.
I. Preliminarily define the antitumor activity of obatoclax hydrochloride in patients with
refractory or relapsed solid tumors or leukemias within the confines of a phase I study.
OUTLINE: This is a multicenter, dose-escalation study of obatoclax mesylate. Patients are
stratified according to disease type (solid tumor or lymphoma [stratum 1] vs multilineage
leukemia (MLL) [stratum 2] vs non-MLL leukemia [stratum 3]) and treated according to
STRATUM 1 (dose-escalation): Patients receive obatoclax mesylate IV over 3 hours on days 1
and 8 and vincristine sulfate IV, doxorubicin hydrochloride IV, and dexrazoxane
hydrochloride IV on day 8 of course 1 (28 days). Drugs are administered on day 1 of
subsequent courses and repeat every 21 days for up to 1 year in the absence of disease
progression or unacceptable toxicity.
STRATUM 2: Patients receive obatoclax mesylate (at starting dose in stratum 1), vincristine
sulfate, doxorubicin hydrochloride, and dexrazoxane hydrochloride as in stratum 1.
STRATUM 3: Patients receive obatoclax mesylate (at the MTD determined in stratum 1),
vincristine sulfate, doxorubicin hydrochloride, and dexrazoxane hydrochloride as in stratum
After completion of study therapy, patients are followed up for 30 days.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum-tolerated dose of obatoclax mesylate in combination with vincristine sulfate, doxorubicin hydrochloride, and dexrazoxane hydrochloride, assessed by Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0)
Children's Oncology Group
United States: Food and Drug Administration
|Baylor College of Medicine||Houston, Texas 77030|
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|Children's National Medical Center||Washington, District of Columbia 20010-2970|
|Cincinnati Children's Hospital Medical Center||Cincinnati, Ohio 45229-3039|
|Children's Hospital of Pittsburgh of UPMC||Pittsburgh, Pennsylvania 15213|
|Oregon Health and Science University||Portland, Oregon 97201|
|Seattle Children's Hospital||Seattle, Washington 98105|
|Childrens Memorial Hospital||Chicago, Illinois 60614|
|Columbia University Medical Center||New York, New York 10032|
|University of Minnesota Medical Center-Fairview||Minneapolis, Minnesota 55455|
|C S Mott Children's Hospital||Ann Arbor, Michigan 48109|
|Childrens Hospital of Orange County||Orange, California 92868-3874|