Obatoclax Mesylate, Vincristine Sulfate, Doxorubicin Hydrochloride, and Dexrazoxane Hydrochloride in Treating Young Patients With Relapsed or Refractory Solid Tumors, Lymphoma, or Leukemia
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
5 other identifiers
interventional
22
2 countries
20
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Jun 2009
Longer than P75 for phase_1
20 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 1, 2009
CompletedFirst Submitted
Initial submission to the registry
July 7, 2009
CompletedFirst Posted
Study publicly available on registry
July 8, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2013
CompletedMay 1, 2014
April 1, 2013
3.8 years
July 7, 2009
April 30, 2014
Conditions
Outcome Measures
Primary Outcomes (2)
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).
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.
Up to 30 days
Secondary Outcomes (1)
Disease response assessed using Response Evaluation Criteria in Solid Tumors
Up to 30 days
Study Arms (1)
Treatment (obatoclax, vincristine, doxorubicin, dexrazoxane)
EXPERIMENTALSTRATUM 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 1.
Interventions
Given IV
Given IV
Given IV
Given IV
Correlative studies
Correlative studies
Eligibility Criteria
You may qualify if:
- Stratum 1 (solid tumors, including lymphomas): patients must have had histologic verification of malignancy at original diagnosis or relapse; patients with recurrent or refractory solid tumors are eligible, excluding primary central nervous system (CNS) tumors or patients with known CNS metastases
- Stratum 2 (mixed-lineage leukemia \[MLL\] + leukemia): patients with recurrent or refractory MLL+ leukemia are eligible excluding those patients with symptomatic CNS leukemia, CNS chloromas, or leptomeningeal leukemic involvement
- Stratum 3 (other leukemias): patients with non-MLL+ recurrent or refractory leukemia (acute lymphoblastic leukemia \[ALL\], acute myeloid leukemia \[AML\] or chronic myeloid leukemia \[CML\] in blast crisis) are eligible excluding those patients with symptomatic CNS leukemia, CNS chloromas, or leptomeningeal leukemic involvement
- Stratum 1: patients must have either measurable or evaluable disease
- Strata 2 and 3: patients with leukemia must have a \> 25% blasts on bone marrow aspirate to be eligible
- Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
- Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
- Myelosuppressive chemotherapy: must not have received within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea); hydroxyurea may be administered prior to study enrollment; in such cases at least 24 hours must have elapsed between the last dose of hydroxyurea and the first dose of obatoclax
- Hematopoietic growth factors: at least 7 days since the completion of therapy with a growth factor
- Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
- Immunotherapy: at least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines
- Monoclonal antibodies: at least 3 half-lives since prior therapy that includes a monoclonal antibody
- Radiation therapy (XRT): \>= 2 weeks (wks) for local palliative XRT (small port); \>= 6 months must have elapsed if prior total-body irradiation (TBI), craniospinal XRT or if \>= 50% radiation of pelvis; \>= 6 wks must have elapsed if other substantial bone marrow (BM) radiation
- Stem cell transplant or rescue without TBI: no evidence of active graft vs. host disease and \>= 3 months must have elapsed since transplant
- +19 more criteria
You may not qualify if:
- Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
- Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment
- Patients requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the prior 7 days
- Patients who are currently receiving another investigational drug are not eligible
- Patients who are currently receiving other anticancer agents, with the exception of hydroxyurea, are not eligible; patients with leukemia may receive intrathecal therapy as outlined
- Any anti-convulsant medications
- Patients who have an uncontrolled infection are not eligible
- Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
- Patients with a total lifetime cumulative anthracycline dose \> 750 mg/m2 (25 mg/kg if \< 1 year) doxorubicin or equivalent at the time of enrollment are not eligible
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (20)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
Childrens Hospital of Orange County
Orange, California, 92868-3874, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60614, United States
Indiana University Medical Center
Indianapolis, Indiana, 46202, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, 55455, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Columbia University Medical Center
New York, New York, 10032, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5, Canada
Related Publications (1)
Urtishak KA, Edwards AY, Wang LS, Hudome A, Robinson BW, Barrett JS, Cao K, Cory L, Moore JS, Bantly AD, Yu QC, Chen IM, Atlas SR, Willman CL, Kundu M, Carroll AJ, Heerema NA, Devidas M, Hilden JM, Dreyer ZE, Hunger SP, Reaman GH, Felix CA. Potent obatoclax cytotoxicity and activation of triple death mode killing across infant acute lymphoblastic leukemia. Blood. 2013 Apr 4;121(14):2689-703. doi: 10.1182/blood-2012-04-425033. Epub 2013 Feb 7.
PMID: 23393050DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Richard Aplenc
COG Phase I Consortium
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 7, 2009
First Posted
July 8, 2009
Study Start
June 1, 2009
Primary Completion
April 1, 2013
Study Completion
April 1, 2013
Last Updated
May 1, 2014
Record last verified: 2013-04