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

NCT01238146 | Withdrawn Phase 1 DMC

• 4 other identifiers: NCI-2011-02536OSU-10040U01CA076576CDR0000687197
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Maximum tolerable dose, defined as the dose level beneath which 2 or more of 6 patients experience DLT (phase I)

  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.

  28 days

• Change in median progression-free survival (PFS) (phase II)

  Estimated using the method of Kaplan-Meier.

  From 6 to 12 months

Secondary Outcomes (2)

• Overall objective response rate (phase II)

  Up to 3 years

• PFS (phase II)

  From the date of start of therapy to disease progression or death, whichever occurs first, assessed at 2 years

Study Arms (2)

Arm I

EXPERIMENTAL

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; Drug: obatoclax mesylate; Biological: rituximab

Arm II

EXPERIMENTAL

Patients receive rituximab and bendamustine hydrochloride as in arm I.

Drug: bendamustine hydrochloride; Biological: rituximab

Interventions

bendamustine hydrochloride DRUG

Given IV

Also known as: bendamustin hydrochloride, bendamustine, cytostasan hydrochloride, Treanda

Arm I; Arm II

obatoclax mesylate DRUG

Given IV

Also known as: GX15-070MS

Arm I

rituximab BIOLOGICAL

Given IV

Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan

Arm I; Arm II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone; Lymphoma, Follicular; Lymphoma, Mantle-Cell

Interventions

Bendamustine Hydrochloride; obatoclax; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Elizabeth Christian

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2010
• First Posted: November 10, 2010
• Study Start: October 1, 2010
• Primary Completion: April 1, 2012
• Last Updated: June 6, 2013

Record last verified: 2013-06

Locations

US (1)