Obatoclax Mesylate, Vincristine Sulfate, Doxorubicin Hydrochloride, and Dexrazoxane Hydrochloride in Treating Young Patients With Relapsed or Refractory Solid Tumors, Lymphoma, or Leukemia

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00933985
First received: July 7, 2009
Last updated: July 1, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Acute Undifferentiated Leukemia
Blastic Phase Chronic Myelogenous Leukemia
Childhood Burkitt Lymphoma
Childhood Chronic Myelogenous Leukemia
Cutaneous B-cell Non-Hodgkin Lymphoma
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Recurrent Childhood Anaplastic Large Cell Lymphoma
Recurrent Childhood Grade III Lymphomatoid Granulomatosis
Recurrent Childhood Large Cell Lymphoma
Recurrent Childhood Lymphoblastic Lymphoma
Recurrent Childhood Small Noncleaved Cell Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent/Refractory Childhood Hodgkin Lymphoma
Relapsing Chronic Myelogenous Leukemia
Secondary Acute Myeloid Leukemia
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: dexrazoxane hydrochloride
Drug: doxorubicin hydrochloride
Drug: obatoclax mesylate
Drug: liposomal vincristine sulfate
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Incidence of adverse events characterized by grade, relationship to study therapy, and prior experience, assessed by CTCAE v4.0 [ Time Frame: Up to 30 days ] [ Designated as safety issue: Yes ]

Enrollment: 52
Study Start Date: June 2009
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I

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.

Drug: dexrazoxane hydrochloride
Given IV
Other Names:
  • Cardioxane
  • Savene
  • Totect
  • Zinecard
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: obatoclax mesylate
Given IV
Other Name: GX15-070MS
Drug: liposomal vincristine sulfate
Given IV
Other Names:
  • liposomal vincristine
  • Marqibo
  • vincristine liposomal
  • vincristine sulfate liposome injection

Detailed Description:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

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.

After completion of study therapy, patients are followed up for 30 days.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of 1 of the following:

    • Histologically confirmed refractory or relapsed solid tumor or lymphoma (stratum 1)

      • Measurable or evaluable disease
      • No primary CNS tumors
      • No known CNS metastases
    • Recurrent or refractory mixed-lineage leukemia (MLL) leukemia (stratum 2)

      • More than 25% blasts on bone marrow aspirate
      • No symptomatic CNS leukemia, CNS chloromas, or leptomeningeal leukemic involvement
    • Recurrent or refractory non-MLL leukemia (stratum 3)

      • Acute lymphoblastic leukemia, acute myeloid leukemia, or chronic myeloid leukemia in blast crisis
      • More than 25% blasts on bone marrow aspirate
      • No symptomatic CNS leukemia, CNS chloromas, or leptomeningeal leukemic involvement
  • No known curative therapy or therapy proven to prolong survival with an acceptable quality of life
  • Karnofsky performance status 50-100% (> 16 years of age)
  • Lansky performance status 50-100% (≤ 16 years of age)
  • ANC ≥ 1,000/mm^3 (stratum 1)
  • Platelet count ≥ 100,000/mm^3 (transfusion independent defined as ≥ 7 days since prior transfusion)(stratum 1)
  • Platelet count ≥ 20,000/mm^3 (may receive platelet transfusion) (stratum 2 and 3)
  • Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusion)
  • Creatinine clearance OR radioisotope GFR ≥ 70 mL/min OR 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 and unconjugated) ≤ 1.5 times upper limit of normal
  • ALT ≤ 110 U/L
  • Serum albumin ≥ 2 g/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Adequate cardiac function defined as 1 of the following:

    • Shortening fraction ≥ 27% by echocardiogram
    • Ejection fraction ≥ 50% by gated radionuclide study
  • Central nervous system function defined as:

    • Stable neurological examination ≥ 2 weeks prior to study
    • No known unresolved neurological toxicities > grade 2
  • No uncontrolled infection
  • Must be able to comply with the safety-monitoring requirements of the study according to the primary investigator's opinion
  • No prior total lifetime cumulative anthracycline dose > 750 mg/m^2 (25 mg/kg if patient < 1 year) of doxorubicin hydrochloride or equivalent (e.g., daunorubicin hydrochloride, idarubicin, or mitoxantrone hydrochloride)
  • Recovered from all prior chemotherapy, immunotherapy, or radiotherapy
  • At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea)

    • At least 24 hours since prior hydroxyurea
  • At least 7 days since prior hematopoietic growth factor
  • At least 7 days since prior biologic therapy

    • Time must be extended for other biological agents known to have adverse events beyond 7 days, at the discretion of the primary investigator
  • At least 6 weeks since prior immunotherapy (e.g., tumor vaccine)
  • At least 3 half-lives since prior monoclonal antibody therapy
  • Prior radiotherapy allowed according to the following criteria:

    • At least 2 weeks since prior palliative radiotherapy (small port)
    • At least 6 months since prior total-body irradiation (TBI), craniospinal radiotherapy, or ≥ 50% radiation of the pelvis
    • At least 6 weeks since other prior substantial bone marrow radiation
  • At least 3 months since prior stem cell transplantation or rescue without TBI and no evidence of active graft-vs-host disease
  • More than 7 days since prior growth factor that supports platelet or white cell number or function
  • Stable or decreasing dose of corticosteroid in the past 7 days
  • No concurrent investigational drugs
  • No other concurrent anticancer agents (including chemotherapy, radiotherapy, immunotherapy, or biologic therapy) except for hydroxyurea

    • Patients with leukemia may receive concurrent anticancer agents (methotrexate, hydrocortisone, cytarabine) intrathecally, if necessary
  • No concurrent anticonvulsants
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00933985

  Show 19 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Richard Aplenc COG Phase I Consortium
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00933985     History of Changes
Other Study ID Numbers: NCI-2011-01936, ADVL0816, COG-ADVL0816, CDR0000647160, U01CA097452
Study First Received: July 7, 2009
Last Updated: July 1, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Blast Crisis
Burkitt Lymphoma
Hodgkin Disease
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphoma
Lymphoma, Non-Hodgkin
Lymphomatoid Granulomatosis
Mycoses
Mycosis Fungoides
Sezary Syndrome
Lymphoma, B-Cell
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Lymphoma, Large-Cell, Anaplastic
Lymphoma, Extranodal NK-T-Cell
Neoplasms
Neoplasms by Histologic Type
Cell Transformation, Neoplastic
Neoplastic Processes
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Pathologic Processes
Epstein-Barr Virus Infections
Herpesviridae Infections

ClinicalTrials.gov processed this record on April 16, 2014