Obatoclax Mesylate, Rituximab, and Bendamustine Hydrochloride in Treating Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

This study has been withdrawn prior to enrollment.
(No patients accrued.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01238146
First received: November 9, 2010
Last updated: June 5, 2013
Last verified: June 2013
  Purpose

This phase I/II trial is studying the side effects and the best dose of obatoclax mesylate when given together with rituximab and bendamustine hydrochloride to see how well it works compared with rituximab and bendamustine hydrochloride alone in treating patients with relapsed or refractory non-Hodgkin lymphoma. Obatoclax mesylate may stop the growth of cancer cells by blocking some of the proteins needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as bendamustine hydrochloride, also 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 rituximab and bendamustine hydrochloride may kill more cancer cells


Condition Intervention Phase
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Nodal Marginal Zone B-cell Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Splenic Marginal Zone Lymphoma
Drug: bendamustine hydrochloride
Drug: obatoclax mesylate
Biological: rituximab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of Rituximab, Bendamustine, and Obatoclax in Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum tolerable dose, defined as the dose level beneath which 2 or more of 6 patients experience DLT (phase I) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Graded using CTCAE version 4 criteria. DLTs are defined as grade 3-4 neutropenia or thrombocytopenia that persists beyond day 42; grade 4 febrile neutropenia or infection; grade 3 febrile neutropenia or infection that fails to resolve within 7days, grade 3-4 somnolence, ataxia, or confusion that requires inpatient admission on day 1 for observation and prevents patient discharge from outpatient clinic, or other grade 3-4 non-hematologic toxicity excluding infection.

  • Change in median progression-free survival (PFS) (phase II) [ Time Frame: From 6 to 12 months ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan-Meier.


Secondary Outcome Measures:
  • Overall objective response rate (phase II) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    95% confidence intervals will be provided.

  • PFS (phase II) [ Time Frame: From the date of start of therapy to disease progression or death, whichever occurs first, assessed at 2 years ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan-Meier.


Enrollment: 0
Study Start Date: October 2010
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive obatoclax mesylate IV over 3 hours on days 1-3, rituximab IV over 4-8 hours on day 1, and bendamustine hydrochloride IV over 30 minutes on days 1-2.
Drug: bendamustine hydrochloride
Given IV
Other Names:
  • bendamustin hydrochloride
  • bendamustine
  • cytostasan hydrochloride
  • Treanda
Drug: obatoclax mesylate
Given IV
Other Name: GX15-070MS
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Experimental: Arm II
Patients receive rituximab and bendamustine hydrochloride as in arm I.
Drug: bendamustine hydrochloride
Given IV
Other Names:
  • bendamustin hydrochloride
  • bendamustine
  • cytostasan hydrochloride
  • Treanda
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed indolent B-cell non-Hodgkin lymphoma (NHL), including any of the following subtypes recognized by WHO classification:

    • Marginal zone lymphoma
    • Lymphoplasmacytic lymphoma
    • Follicular lymphoma
    • Mantle cell lymphoma
  • Transformed lymphoma from a low-grade, indolent NHL allowed provided patient has received ≥ 1 prior therapy for indolent disease
  • Must have received ≥ 1 prior therapy
  • Relapsed disease after autologous or allogeneic stem cell transplantation (SCT) allowed (phase I)

    • No relapse after allogeneic SCT (phase II)
  • No known CNS lymphoma
  • ECOG performance status 0-2
  • ANC ≥ 1,000/µL
  • Platelet count ≥ 50,000/µL
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN
  • Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 50 mL/min
  • Not pregnant or nursing
  • Fertile patients must use effective contraception prior to and for the duration of study participation
  • No active hepatitis B infection

    • Patients with a history of hepatitis B (surface antigen or core antibody positive) must take lamivudine or equivalent during study therapy
  • No history of documented human anti-globulin antibodies, or a history of allergic reactions attributed to compounds of similar chemical or biologic composition to rituximab, bendamustine hydrochloride, or obatoclax mesylate
  • No uncontrolled intercurrent illness including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness and/or social situations that would limit compliance with study requirements
  • HIV infection allowed provided patient meets the following criteria:

    • No evidence of co-infection with hepatitis B or C
    • CD4 cell count ≥ 400/mm³
    • No evidence of resistant strains of HIV
    • HIV viral load ≤ 10,000 copies HIV RNA/mL for patients not on anti-HIV combination antiretroviral therapy OR HIV viral load ≤ 50,000 copies HIV RNA/mL for patients on anti-HIV therapy
    • No history of AIDS-defining conditions
  • No active secondary malignancy except for non-melanomatous skin cancer
  • No other concurrent investigational agents
  • Prior bendamustine hydrochloride allowed provided patient has completed a bendamustine-containing regimen within the past 6 months and achieved a partial response or better
  • More than 4 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01238146

Locations
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Investigators
Principal Investigator: Elizabeth Christian Ohio State University Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01238146     History of Changes
Other Study ID Numbers: NCI-2011-02536, OSU-10040, U01CA076576, CDR0000687197
Study First Received: November 9, 2010
Last Updated: June 5, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma, B-Cell
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Mantle-Cell
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Bendamustine
Nitrogen Mustard Compounds
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014