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

Recurrent Mantle Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00538187
• Other study ID #: NCI-2009-00253
• Secondary ID: PHI-58CDR0000566
• Status: Terminated
• Phase: Phase 1
• First received: October 1, 2007
• Last updated: December 3, 2015
• Start date: December 2007

Study information

• Verified date: May 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 18
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adult Non-Hodgkin Lymphoma
• Leukemia, Lymphocytic, Chronic, B-Cell
• Lymphoma
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• 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

Intervention

Drug:
• obatoclax mesylate
Given IV
• bortezomib
Given IV

Other:
• laboratory biomarker analysis
correlative study
• pharmacological study
correlative study

Locations

Country	Name	City	State
United States	City of Hope Medical Center	Duarte	California

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of obatoclax mesylate when administered with bortezomib	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	Yes
Secondary	Toxicity as assessed by NCI CTCAE version 3.0	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	Yes
Secondary	Pharmacokinetics of obatoclax mesylate when administered with bortezomib		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	No