Obatoclax Mesylate, Vincristine Sulfate, Doxorubicin Hydrochloride, and Dexrazoxane Hydrochloride in Treating Young Patients With Relapsed or Refractory Solid Tumors, Lymphoma, or Leukemia
NCT ID: NCT00933985
Last Updated: 2014-05-01
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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TERMINATED
PHASE1
22 participants
INTERVENTIONAL
2009-06-30
2013-04-30
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment (obatoclax, vincristine, doxorubicin, dexrazoxane)
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 1.
dexrazoxane hydrochloride
Given IV
doxorubicin hydrochloride
Given IV
obatoclax mesylate
Given IV
liposomal vincristine sulfate
Given IV
pharmacological study
Correlative studies
laboratory biomarker analysis
Correlative studies
Interventions
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dexrazoxane hydrochloride
Given IV
doxorubicin hydrochloride
Given IV
obatoclax mesylate
Given IV
liposomal vincristine sulfate
Given IV
pharmacological study
Correlative studies
laboratory biomarker analysis
Correlative studies
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* STRATUM 1: Peripheral absolute neutrophil count (ANC) \>= 1000/mm\^3
* STRATUS 1: Platelet count \>= 100,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)
* STRATUM 1: Hemoglobin \>= 8.0 g/dL (may receive red blood cell \[RBC\] transfusions)
* STRATA 2 and 3: Platelet count \>= 20,000/mm\^3 (may receive platelet transfusions)
* STRATA 2 and 3: Hemoglobin \>= 8.0 g/dL (may receive RBC transfusions)
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70ml/min/1.73 m\^2 OR a serum creatinine based on age/gender as follows:
* 0.5 mg/dL (6 months to \< 1 year of age)
* 0.6 mg/dL (1 to \< 2 years of age)
* 0.8 mg/dL (2 to \< 6 years of age)
* 1 mg/dL (6 to \< 10 years of age)
* 1.2 mg/dL (10 to \< 13 years of age)
* 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to \< 16 years of age)
* 1.7 mg/dL (male) or 1.4 mg/dL (female) (\>= 16 years of age)
* Bilirubin (sum of conjugated + unconjugated) \>= 1.5 x upper limit of normal (ULN) for age
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \>= 110 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L
* Serum albumin \>= 2 g/dL
* Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \>= 50% by gated radionuclide study
* Stable neurological examination for at least 2 weeks prior to study enrollment; no known \> grade 2 unresolved neurological toxicities
* All patients and/or their parents or legal guardians must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
Exclusion Criteria
* 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
21 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Richard Aplenc
Role: PRINCIPAL_INVESTIGATOR
COG Phase I Consortium
Locations
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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
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Oregon Health and Science University
Portland, Oregon, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
University of Texas Southwestern Medical Center
Dallas, Texas, United States
Baylor College of Medicine
Houston, Texas, United States
Seattle Children's Hospital
Seattle, Washington, United States
Hospital for Sick Children
Toronto, Ontario, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, Canada
Countries
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References
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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.
Other Identifiers
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NCI-2011-01936
Identifier Type: REGISTRY
Identifier Source: secondary_id
COG-ADVL0816
Identifier Type: -
Identifier Source: secondary_id
CDR0000647160
Identifier Type: -
Identifier Source: secondary_id
ADVL0816
Identifier Type: OTHER
Identifier Source: secondary_id
ADVL0816
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2011-01936
Identifier Type: -
Identifier Source: org_study_id
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