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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00538187
First received: October 1, 2007
Last updated: May 1, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Adult Non-Hodgkin Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Small Lymphocytic Lymphoma
Drug: obatoclax mesylate
Drug: bortezomib
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of GX15-070 (NSC # 729280) and Bortezomib in Aggressive Relapsed/Recurrent Non-Hodgkin's Lymphoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum tolerated dose of obatoclax mesylate when administered with bortezomib [ Time Frame: 35 days ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Toxicity as assessed by NCI CTCAE version 3.0 [ Time Frame: Up to 26 weeks after completion of study treatment ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: December 2007
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: obatoclax mesylate
Given IV
Other Name: GX15-070MS
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Other: laboratory biomarker analysis
correlative study
Other: pharmacological study
correlative study
Other Name: pharmacological studies

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.

  Eligibility

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

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
  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: NCT00538187

Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
Sponsors and Collaborators
Investigators
Principal Investigator: Joseph Tuscano City of Hope Medical Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00538187     History of Changes
Other Study ID Numbers: NCI-2009-00253, PHI-58, CDR0000566357, U01CA062505
Study First Received: October 1, 2007
Last Updated: May 1, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Large B-Cell, Diffuse
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Leukemia, B-Cell
Leukemia, Lymphoid
Leukemia
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014