Obatoclax and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma

NCT00719901 | Terminated Phase 1 Results

• 9 other identifiers: NCI-2009-00255CDR0000597950MAYO-MC068AMC068A7952N01CM62205P01CA136447N01CM62208N01CM62203
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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 relapsed or refractory multiple myeloma. Obatoclax and bortezomib 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.

Conditions

Refractory Multiple Myeloma; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Number of Dose-limiting Toxicity (DLT) Incidents (Phase I)

  DLT was defined as any events that is determined to be possibly, probably, or definitely related to the combination of bortezomib and GX15-070 (as determined by the investigator) and occurring during the first cycle of treatment, irrespective of whether the toxicity resolved. Hematologic DLT measures were assessed using the continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization via Common Terminology Criteria for Adverse Events (CTCAE) version 3 standard toxicity grading.

  Up to 21 days of every first course

• Proportion of Patients Who Achieve a Partial Response or Better. (Phase II)

  In order to be classified as a hematologic response, confirmation of serum monoclonal protein, serum immunoglobulin free light chain (when primary determinant of response) and urine monoclonal protein (when primary determinant of response) results must be made by verification on two consecutive determinations.

  From baseline to up to 3 years

Secondary Outcomes (5)

• Number of Patients Who Have at Least a Partial Response (Phase I)

  From baseline to up to 3 years

• Time to Progression (Phase II)

  Time from registration to the time of progression

• Overall Survival (Phase II)

  Time from registration to death due to any cause

• Time to Treatment Failure (Phase II)

  Time from study entry to the date patients end treatment

• Toxicity as Assessed by the National Cancer Institute (NCI) CTCAE v 3.0 (Phase II)

  From baseline to up to 3 years

Study Arms (1)

Treatment (enzyme inhibitor therapy)

EXPERIMENTAL

Patients receive obatoclax mesylate IV over 3 hours and bortezomib IV on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: obatoclax mesylate; Drug: bortezomib; Other: laboratory biomarker analysis

Interventions

obatoclax mesylate DRUG

Given IV

Also known as: GX15-070MS

Treatment (enzyme inhibitor therapy)

bortezomib DRUG

Given IV

Also known as: LDP 341, MLN341, VELCADE

Treatment (enzyme inhibitor therapy)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (enzyme inhibitor therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Symptomatic multiple myeloma, meeting the following criteria at original diagnosis:
• Bone marrow plasmacytosis with ≥ 10% plasma cells or sheets of plasma cells or biopsy proven plasmacytoma
• Symptomatic disease (e.g.,anemia, hypercalcemia, bone disease, or renal dysfunction) that requires the initiation of therapy
• Measurable diseases assessed by one of the following:
• Monoclonal plasma cells detectable in the bone marrow
• Monoclonal serum spike detectable by serum protein electrophoresis or immunofixation
• Monoclonal protein detectable in the urine by electrophoresis or immunofixation
• Abnormal levels of the serum free light chains with an abnormal ratio between kappa and lambda
• Progressive disease after ≥ 1 prior therapy for myeloma
• Previously treated with ≤ 10 courses (30 weeks) of bortezomib and had no disease progression during therapy OR completed bortezomib therapy within the past 6 weeks
• No prior discontinuation of bortezomib therapy due to drug intolerance
• No known brain metastases
• No intracranial edema, intracranial metastasis, or active epidural disease
• Patients with lytic lesions of the cranium secondary to myeloma are eligible
• ECOG performance status 0-2

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

obatoclax; Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

This trial was terminated due to slow accrual and the drug supply of Obatoclax during the phase I; therefore, the phase II portion will never open. No results from the phase II portion are available.

Results Point of Contact

• Title: A. Keith Stewart
• Organization: Mayo Clinic

stewart.keith@mayo.edu

480-301-4411

Study Officials

• Alexander Stewart

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2008
• First Posted: July 22, 2008
• Study Start: July 1, 2008
• Primary Completion: April 1, 2011
• Study Completion: June 1, 2012
• Last Updated: January 12, 2015
• Results First Posted: December 9, 2013

Record last verified: 2013-10

Locations

US (1)