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Obatoclax and Bortezomib in Treating Patients With Aggressive Relapsed or Recurrent Non-Hodgkin Lymphoma
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), December 2008
Sponsors and Collaborators: California Cancer Consortium
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00538187
  Purpose

RATIONALE: 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.

PURPOSE: 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
Lymphoma
Drug: bortezomib
Drug: obatoclax mesylate
Procedure: immunoenzyme technique
Procedure: immunohistochemistry staining method
Procedure: laboratory biomarker analysis
Procedure: pharmacological study
Phase I
Phase II

MedlinePlus related topics: Cancer Lymphoma
Drug Information available for: Bortezomib
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: Phase I Study of GX15-070 (NSC # 729280) and Bortezomib in Aggressive Relapsed/Recurrent Non-Hodgkin's Lymphoma

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

Primary Outcome Measures:
  • Maximum tolerated dose of obatoclax mesylate when administered with bortezomib [ Designated as safety issue: Yes ]
  • Toxicity as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics of obatoclax mesylate when administered with bortezomib [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: December 2007
Estimated Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • To establish the maximum tolerated dose of obatoclax mesylate when administered with bortezomib in patients with aggressive relapsed or recurrent non-Hodgkin lymphoma.
  • To describe the toxicities of this regimen at each dose studied in these patients.
  • To characterize the pharmacokinetic behavior of this regimen in these patients.
  • To obtain preliminary information regarding the effect of obatoclax mesylate on several apoptotic regulatory pathways.
  • 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.

Archival (pre-study) surgical specimens, including fixed paraffin-embedded diagnostic tissue blocks, are collected for immunohistochemical analysis of the Bcl-2 family members, p53, Noxa, and Puma proteins. Serial blood samples are collected at baseline, day 8, and day 15 for cytochrome C analysis via enzyme-linked immunosorbent assay and plasma and buffy coat analysis.

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

DISEASE CHARACTERISTICS:

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)

    • 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

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • Karnofsky performance status 60-100%
  • Life expectancy > 3 months
  • WBC ≥ 3,000/mm³
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • 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

Exclusion criteria:

  • History of allergic reactions attributed to bortezomib, polyethylene glycol (PEG 300), or polysorbate 20
  • 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
  • Psychiatric illness or social situation that would limit compliance with study requirements
  • Patients who are intolerant or refractory to prior treatment with bortezomib (refractory is defined as no response to prior treatment with bortezomib)

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

  • See Disease Characteristics
  • At least 4 weeks since prior radiotherapy
  • More than 2 days since prior steroids
  • More than 2 weeks since prior low-dose chlorambucil
  • At least 2 weeks since prior valproic acid

Exclusion criteria:

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00538187

Locations
United States, California
City of Hope Comprehensive Cancer Center Recruiting
Duarte, California, United States, 91010-3000
Contact: Clinical Trials Office - City of Hope Comprehensive Cancer Cen     800-826-4673     becomingapatient@coh.org    
City of Hope Medical Group Recruiting
Pasadena, California, United States, 91105
Contact: Mark V. McNamara, MD     626-396-2900     mmcnamara@ccsmg.com    
Contra Costa Regional Medical Center Recruiting
Martinez, California, United States, 94553
Contact: Sharon Hiner, MD     925-370-5114     shiner@hsd.co.contra-costa.ca.us    
USC/Norris Comprehensive Cancer Center and Hospital Recruiting
Los Angeles, California, United States, 90089-9181
Contact: Clinical Trials Office - USC/Norris Comprehensive Cancer Cente     323-865-0451        
Veterans Affairs Outpatient Clinic - Martinez Recruiting
Martinez, California, United States, 94553
Contact: Ted Wun, MD     925-372-2062        
United States, Pennsylvania
Penn State Cancer Institute at Milton S. Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033-0850
Contact: Clinical Trials Office - Penn State Cancer Institute at Milton     717-531-3779     CTO@hmc.psu.edu    
UPMC Cancer Centers Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Clinical Trials Office - UPMC Cancer Centers     412-647-8073        
Sponsors and Collaborators
California Cancer Consortium
Investigators
Study Chair: Joseph M. Tuscano, MD University of California, Davis
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Study ID Numbers: CDR0000566357, CCC-PHI-58
Study First Received: October 1, 2007
Last Updated: December 9, 2008
ClinicalTrials.gov Identifier: NCT00538187  
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent marginal zone lymphoma
recurrent mantle cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent small lymphocytic lymphoma

Study placed in the following topic categories:
Chronic lymphocytic leukemia
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Leukemia, B-cell, chronic
Lymphoma, Mantle-Cell
Bortezomib
Lymphoma, Follicular
Lymphoma, small cleaved-cell, diffuse
Mantle cell lymphoma
Recurrence
Lymphoma, large-cell
Lymphatic Diseases
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Non-Hodgkin
Aggression
Lymphoproliferative Disorders
Lymphoma
Follicular lymphoma

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Pharmacologic Actions
Protease Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009