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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00538187
Recruitment Status : Terminated
First Posted : October 2, 2007
Last Update Posted : December 4, 2015
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
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 or disease Intervention/treatment 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

Detailed Description:


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  (Clinical Trial)
Actual Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : December 2007
Actual Primary Completion Date : April 2011

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: obatoclax mesylate
Given IV
Other Name: GX15-070MS

Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341

Other: laboratory biomarker analysis
correlative study

Other: pharmacological study
correlative study
Other Name: pharmacological studies

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. 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 ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00538187

United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Joseph Tuscano City of Hope Medical Center

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00538187     History of Changes
Other Study ID Numbers: NCI-2009-00253
U01CA062505 ( U.S. NIH Grant/Contract )
First Posted: October 2, 2007    Key Record Dates
Last Update Posted: December 4, 2015
Last Verified: May 2013

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