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

NCT ID: NCT00538187

Last Updated: 2015-12-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (obatoclax mesylate, bortezomib)

Patients will receive a 3-hour infusion of obatoclax and an infusion of bortezomib once a week for 4 weeks

Group Type EXPERIMENTAL

obatoclax mesylate

Intervention Type DRUG

Given IV

bortezomib

Intervention Type DRUG

Given IV

laboratory biomarker analysis

Intervention Type OTHER

correlative study

pharmacological study

Intervention Type OTHER

correlative study

Interventions

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obatoclax mesylate

Given IV

Intervention Type DRUG

bortezomib

Given IV

Intervention Type DRUG

laboratory biomarker analysis

correlative study

Intervention Type OTHER

pharmacological study

correlative study

Intervention Type OTHER

Other Intervention Names

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GX15-070MS LDP 341 MLN341 VELCADE pharmacological studies

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Joseph Tuscano

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

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City of Hope Medical Center

Duarte, California, United States

Site Status

Countries

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United States

Other Identifiers

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PHI-58

Identifier Type: -

Identifier Source: secondary_id

CDR0000566357

Identifier Type: -

Identifier Source: secondary_id

U01CA062505

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00253

Identifier Type: -

Identifier Source: org_study_id