This phase I trial is studying the side effects and best dose of obatoclax mesylate when given together with vincristine sulfate, doxorubicin hydrochloride, and dexrazoxane hydrochloride in treating young patients with relapsed or refractory solid tumors, lymphoma, or leukemia. Obatoclax mesylate may stop the growth of cancer cells by blocking some of the proteins needed for cell growth and causing the cells to self-destruct. Drugs used in chemotherapy, such as vincristine sulfate, doxorubicin hydrochloride, and dexrazoxane hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving obatoclax mesylate together with combination chemotherapy may kill more cancer cells.
PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) and/or recommended Phase II dose of obatoclax (obatoclax mesylate) administered as a single agent on day 1 and in combination with vincristine ( vincristine sulfate), doxorubicin (doxorubicin hydrochloride), and dexrazoxane (dexrazoxane hydrochloride) at day 8 in children with refractory solid tumors. II. To define and describe the toxicities of obatoclax administered on this schedule. III. To characterize the pharmacokinetics of obatoclax in children with refractory solid tumors or relapsed leukemia. SECONDARY OBJECTIVES: I. To preliminarily define the antitumor activity of obatoclax in children with refractory or relapsed solid tumors and leukemias within the confines of a Phase I study. II. To preliminarily assess leukemic blast characteristics associated with obatoclax activity. III. To preliminarily assess the biological activity of obatoclax by investigating effects on cell death regulatory pathways. OUTLINE: This is a dose-escalation study of obatoclax mesylate. STRATUM 1 (dose-escalation): Patients receive obatoclax mesylate intravenously (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 1. After completion of study therapy, patients are followed up for 30 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
22
Given IV
Given IV
Given IV
Given IV
Correlative studies
Correlative studies
University of Alabama at Birmingham
Birmingham, Alabama, United States
Childrens Hospital of Orange County
Orange, California, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
Indiana University Medical Center
Indianapolis, Indiana, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, United States
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, United States
Washington University School of Medicine
St Louis, Missouri, United States
Columbia University Medical Center
New York, New York, United States
...and 10 more locations
Maximum-tolerated dose of obatoclax mesylate in combination with vincristine sulfate, doxorubicin hydrochloride, and dexrazoxane hydrochloride, defined as the maximum dose at which fewer than one-third of patients experience dose limiting toxicity
Will be assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).
Time frame: 28 days
Incidence of adverse events characterized by grade, relationship to study therapy, and prior experience, assessed by NCI CTCAE v4.0
Descriptive summary of all toxicities will be reported.
Time frame: Up to 30 days
Disease response assessed using Response Evaluation Criteria in Solid Tumors
Time frame: Up to 30 days
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