Obatoclax and Bortezomib in Treating Patients With Aggressive Relapsed or Recurrent Non-Hodgkin Lymphoma
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
Other: laboratory biomarker analysis
Other: pharmacological study
|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|
- 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.
- 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 ]
|Study Start Date:||December 2007|
|Primary Completion Date:||April 2011 (Final data collection date for primary outcome measure)|
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
Other Name: GX15-070MSDrug: bortezomib
Other Names:Other: laboratory biomarker analysis
correlative studyOther: pharmacological study
Other Name: pharmacological studies
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00538187
|United States, California|
|City of Hope Medical Center|
|Duarte, California, United States, 91010|
|Principal Investigator:||Joseph Tuscano||City of Hope Medical Center|