Obatoclax and Bortezomib in Treating Patients With Aggressive Relapsed or Recurrent Non-Hodgkin Lymphoma

December 3, 2015 updated by: National Cancer Institute (NCI)

Phase I Study of GX15-070 (NSC # 729280) and Bortezomib in Aggressive Relapsed/Recurrent Non-Hodgkin's Lymphoma

Obatoclax may stop the growth of non-Hodgkin lymphoma by blocking blood flow to the cancer. Bortezomib and obatoclax may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving obatoclax together with bortezomib may kill more cancer cells. This phase I/II trial is studying the side effects and best dose of obatoclax when given together with bortezomib and to see how well they work in treating patients with aggressive relapsed or recurrent non-Hodgkin lymphoma.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To establish the maximum tolerated dose of obatoclax mesylate when administered with bortezomib in patients with aggressive relapsed or recurrent non-Hodgkin lymphoma.

II. To describe the toxicities of this regimen at each dose studied in these patients.

III. To characterize the pharmacokinetic behavior of this regimen in these patients.

IV. To obtain preliminary information regarding the effect of obatoclax mesylate on several apoptotic regulatory pathways.

V. To document all clinical responses in these patients to this regimen.

OUTLINE: This is a multicenter study.

PHASE I: Patients receive obatoclax mesylate IV over 3 hours followed by bortezomib IV on days 1, 8, 15, and 22.

Treatment repeats every 35 days in the absence of disease progression or unacceptable toxicity. Pharmacokinetic evaluations of obatoclax mesylate are conducted in all patients during the first course.

PHASE II: Patients receive obatoclax mesylate IV over 3 hours followed by bortezomib IV on days 1, 8, 15, and 22 at the maximum tolerated dose determined in phase I.

Treatment repeats every 35 days for up to 1 year in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed for 26 weeks.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed relapsed or refractory non-Hodgkin lymphoma for which standard curative or palliative measures do not exist or are no longer effective, including any of the following subtypes:

    • Follicular grade I, II, or III lymphoma
    • Marginal zone lymphoma
    • Mantle cell lymphoma
    • Diffuse large B cell lymphoma
    • Small lymphocytic lymphoma

  • Must have had at least one prior chemotherapeutic regimen:

    • Steroids or rituximab alone or local radiotherapy do not count as regimens
    • Tositumomab or ibritumomab tiuxetan allowed as regimens
  • Clear evidence of disease progression or lack of response after the most recent therapy, including rituximab or local radiotherapy, is required
  • At least 3 months since prior autologous stem cell transplantation and relapsed (>= 1 year since prior allogeneic transplantation and relapsed) and no active related infections (i.e., fungal or viral)
  • In the case of allogeneic transplantation relapse, there should be no active acute graft-versus-host disease (GVHD) of any grade and no chronic GVHD other than mild skin, oral, or ocular GVHD not requiring systemic immunosuppression
  • No known active brain metastases, other neurological disorders/dysfunction or history of seizure disorder, or other neurological dysfunction
  • Karnofsky performance status 60-100%
  • Life expectancy > 3 months
  • Total bilirubin normal
  • AST and ALT =< 2.5 times upper limit of normal
  • Creatinine normal or creatinine clearance >= 60 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective double-barrier contraception during and for 3 months after the last dose of obatoclax mesylate
  • At least 4 weeks since prior radiotherapy
  • More than 2 days since prior steroids
  • More than 2 weeks since prior low-dose chlorambucil
  • WBC >= 3,000/mm^3
  • ANC >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • At least 2 weeks since prior valproic acid

Exclusion Criteria:

  • Uncontrolled concurrent medical condition or illness including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia including QTc > 450 msec
  • Patients who are intolerant or refractory to prior treatment with bortezomib (refractory is defined as no response to prior treatment with bortezomib)
  • Chemotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C)
  • Rituximab within the past 3 months (unless there is evidence of progression)
  • Patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Other concurrent investigational agents
  • Combination antiretroviral therapy for HIV-positive patients
  • No history of allergic reactions attributed to bortezomib, polyethylene glycol (PEG 300), or polysorbate 20
  • No psychiatric illness or social situation that would limit compliance with study requirements

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (obatoclax mesylate, bortezomib)
Patients will receive a 3-hour infusion of obatoclax and an infusion of bortezomib once a week for 4 weeks
Drug: bortezomib
Given IV
Other Names:
  • MLN341
  • LDP 341
  • VELCADE
Other: pharmacological study
correlative study
Other Names:
  • pharmacological studies
Other: laboratory biomarker analysis
correlative study
Drug: obatoclax mesylate
Given IV
Other Names:
  • GX15-070MS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose of obatoclax mesylate when administered with bortezomib
Time Frame: 35 days
Defined as the highest dose tested in which fewer than 33% of patients experienced DLT attributable to the study drug(s), when at least six patients were treated at that dose and are evaluable for toxicity. Graded according to the NCI CTCAE, Version 3.0.
35 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Toxicity as assessed by NCI CTCAE version 3.0
Time Frame: Up to 26 weeks after completion of study treatment
Summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity and nadir or maximum values for the laboratory measures, time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.
Up to 26 weeks after completion of study treatment
Pharmacokinetics of obatoclax mesylate when administered with bortezomib
Time Frame: Dose 1 of course 1, pre-infusion, 1 and 2 hours into the infusion, immediately prior to the end of the infusion, then at 0.25, 0.5, 1, 2, 4, 8, 24, 48, 72, and 168 hours
Dose 1 of course 1, pre-infusion, 1 and 2 hours into the infusion, immediately prior to the end of the infusion, then at 0.25, 0.5, 1, 2, 4, 8, 24, 48, 72, and 168 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Joseph Tuscano, City of Hope Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2007

Primary Completion (Actual)

April 1, 2011

Study Registration Dates

First Submitted

October 1, 2007

First Submitted That Met QC Criteria

October 1, 2007

First Posted (Estimate)

October 2, 2007

Study Record Updates

Last Update Posted (Estimate)

December 4, 2015

Last Update Submitted That Met QC Criteria

December 3, 2015

Last Verified

May 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2009-00253
  • U01CA062505 (U.S. NIH Grant/Contract)
  • PHI-58
  • CDR0000566357

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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