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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00719901
First received: July 19, 2008
Last updated: October 17, 2013
Last verified: October 2013
  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 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.


Condition Intervention Phase
Refractory Multiple Myeloma
Stage I Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Drug: obatoclax mesylate
Drug: bortezomib
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of Obatoclax Mesylate (GX15-070MS) in Combination With Bortezomib for the Treatment of Relapsed Multiple Myeloma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of Dose-limiting Toxicity (DLT) Incidents (Phase I) [ Time Frame: Up to 21 days of every first course ] [ Designated as safety issue: Yes ]
    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.

  • Proportion of Patients Who Achieve a Partial Response or Better. (Phase II) [ Time Frame: From baseline to up to 3 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Patients Who Have at Least a Partial Response (Phase I) [ Time Frame: From baseline to up to 3 years ] [ Designated as safety issue: No ]
    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.

  • Time to Progression (Phase II) [ Time Frame: Time from registration to the time of progression ] [ Designated as safety issue: No ]
    The distribution of time to progression will be estimated using the method of Kaplan-Meier.

  • Overall Survival (Phase II) [ Time Frame: Time from registration to death due to any cause ] [ Designated as safety issue: No ]
    The distribution of overall survival will be estimated using the method of Kaplan-Meier.

  • Time to Treatment Failure (Phase II) [ Time Frame: Time from study entry to the date patients end treatment ] [ Designated as safety issue: No ]
    Time to treatment failure will be evaluated using the method of Kaplan-Meier.

  • Toxicity as Assessed by the National Cancer Institute (NCI) CTCAE v 3.0 (Phase II) [ Time Frame: From baseline to up to 3 years ] [ Designated as safety issue: Yes ]
    Toxicity is defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. In addition, we will review all toxicities data that is graded as 3, 4, or 5 and classified as either "unrelated or unlikely to be related" to study treatment in the event of an actual relationship developing. Adverse events and toxicities will be evaluated using all patients who have received any study treatment.


Enrollment: 11
Study Start Date: July 2008
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (enzyme inhibitor therapy)
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
Given IV
Other Name: GX15-070MS
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose and recommended phase II dose of obatoclax mesylate when given in combination with bortezomib in patients with relapsed or refractory multiple myeloma. (Phase I) II. To evaluate the response rate (complete response, partial response, and very good partial response) in patients treated with this regimen. (Phase II)

SECONDARY OBJECTIVES:

I. To determine the duration of progression-free and overall survival of these patients.

II. To evaluate the incidence of toxicities of this regimen in these patients. III. To explore the utility of genetic markers based on initial evidence that they are predictive of drug responsiveness and/or successful target inhibition.

OUTLINE: This is a multicenter, phase I, dose-escalation study of obatoclax mesylate followed by a phase II study.

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.

After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Life expectancy > 6 months
  • ANC ≥ 1,000/mm³
  • Platelet count ≥ 50,000/mm³
  • Bilirubin normal
  • AST and ALT ≤ 2.5 times upper limit of normal (ULN)
  • Creatinine ≤ 2 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No peripheral neuropathy > NCI toxicity grade 2
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to obatoclax mesylate or bortezomib
  • No concurrent uncontrolled illness including, but not limited to the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia, including QTc > 450 msec
    • Psychiatric illness/social situations that would limit compliance with study requirements
  • No history of seizure disorder
  • No other neurological disorder or dysfunction that, in the opinion of the investigator, would confound the evaluation of neurologic and other adverse events associated with obatoclax mesylate
  • At least 14 days since prior chemotherapy and recovered
  • More than 28 days since prior experimental drugs and/or investigational agents
  • No concurrent CYP interactive medications
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent anticancer therapy

    • Growth factors and bisphosphonates are allowed as medically indicated
    • Prednisone (≤ 10 mg per day) allowed provided there has been no dose increase within the past 2 weeks
  • No other concurrent investigational agents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00719901

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Alexander Stewart Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00719901     History of Changes
Obsolete Identifiers: NCT01647048
Other Study ID Numbers: NCI-2009-00255, NCI-2009-00255, CDR0000597950, MAYO-MC068A, MC068A, 7952, N01CM62205, P01CA136447, N01CM62208, N01CM62203
Study First Received: July 19, 2008
Results First Received: August 8, 2013
Last Updated: October 17, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Bortezomib
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014