- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00719901
Obatoclax and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma
A Phase I/II Trial of Obatoclax Mesylate (GX15-070MS) in Combination With Bortezomib for the Treatment of Relapsed Multiple Myeloma
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Minnesota
-
Rochester, Minnesota, United States, 55905
- Mayo Clinic
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Dose-limiting Toxicity (DLT) Incidents (Phase I)
Time Frame: Up to 21 days of every first course
|
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)
Time Frame: From baseline to up to 3 years
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Patients Who Have at Least a Partial Response (Phase I)
Time Frame: From baseline to up to 3 years
|
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
|
Time to Progression (Phase II)
Time Frame: Time from registration to the time of progression
|
The distribution of time to progression will be estimated using the method of Kaplan-Meier.
|
Time from registration to the time of progression
|
Overall Survival (Phase II)
Time Frame: Time from registration to death due to any cause
|
The distribution of overall survival will be estimated using the method of Kaplan-Meier.
|
Time from registration to death due to any cause
|
Time to Treatment Failure (Phase II)
Time Frame: Time from study entry to the date patients end treatment
|
Time to treatment failure will be evaluated using the method of Kaplan-Meier.
|
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)
Time Frame: From baseline to up to 3 years
|
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.
|
From baseline to up to 3 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Alexander Stewart, Mayo Clinic
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Bortezomib
- Obatoclax
Other Study ID Numbers
- NCI-2009-00255 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- N01CM62203 (U.S. NIH Grant/Contract)
- N01CM62205 (U.S. NIH Grant/Contract)
- 7952 (Other Identifier: CTEP)
- N01CM62208 (U.S. NIH Grant/Contract)
- CDR0000597950
- MAYO-MC068A
- MC068A (Other Identifier: Mayo Clinic)
- P01CA136447 (Other Grant/Funding Number: US NIH Grant/Contract Award Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Stage I Multiple Myeloma
-
Fred Hutchinson Cancer Research Center/University...National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Mayo ClinicCompletedMultiple Myeloma | Stage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
City of Hope Medical CenterCompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
University of WashingtonNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Barbara Ann Karmanos Cancer InstituteNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Lawson Health Research InstituteThe Ottawa Hospital; Hamilton Health Sciences Corporation; Dalhousie University; Niagara Health SystemActive, not recruitingMultiple Myeloma in Relapse | Multiple Myeloma With Failed Remission | Multiple Myeloma Stage I | Multiple Myeloma Progression | Multiple Myeloma Stage II | Multiple Myeloma Stage IIICanada
Clinical Trials on laboratory biomarker analysis
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletedProstate Cancer
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingLeukemia | Acute Lymphoblastic Leukemia | Acute Promyelocytic LeukemiaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedUntreated Adult Acute Lymphoblastic Leukemia | Untreated Childhood Acute Lymphoblastic LeukemiaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Lymphoblastic Leukemia in Remission | Recurrent Childhood Acute Lymphoblastic LeukemiaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedLung CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)WithdrawnClear Cell Renal Cell Carcinoma | Rhabdoid Tumor of the Kidney | Congenital Mesoblastic Nephroma | Childhood Kidney NeoplasmUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)WithdrawnBreast Carcinoma | BRCA1 Mutation Carrier | BRCA2 Mutation CarrierUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedWilms Tumor and Other Childhood Kidney TumorsUnited States