A Phase I/II Trial of Obatoclax Mesylate (GX15-070MS) in Combination With Bortezomib for the Treatment of Relapsed Multiple Myeloma
18 Years
N/A
Both
Refractory Multiple Myeloma, Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma
Trial Information
A Phase I/II Trial of Obatoclax Mesylate (GX15-070MS) in Combination With Bortezomib for the Treatment of Relapsed Multiple Myeloma
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.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Number of dose-limiting toxicity (DLT) incidents (Phase I)
Outcome Description:
DLT will be 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 will be 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.
Outcome Time Frame:
Up to 21 days of every first course
Safety Issue:
Yes
Principal Investigator
Alexander Stewart
Investigator Role:
Principal Investigator
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00255
NCT ID:
NCT00719901
Start Date:
July 2008
Completion Date:
Related Keywords:
- Refractory Multiple Myeloma
- Stage I Multiple Myeloma
- Stage II Multiple Myeloma
- Stage III Multiple Myeloma
- Multiple Myeloma
- Neoplasms, Plasma Cell
Name | Location |
|---|---|
| Mayo Clinic | Rochester, Minnesota 55905 |
