Study of ACY-1215 Alone and in Combination With Bortezomib and Dexamethasone in Multiple Myeloma
- Registration Number
- NCT01323751
- Lead Sponsor
- Celgene
- Brief Summary
Phase 1(a \& b): To evaluate the side effects and determine the best dose of oral ACY-1215 as monotherapy, and also in combination with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma.
Phase 2a: To determine the objective response rate of oral ACY-1215 in combination with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 120
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Patient has relapsed or relapsed/refractory MM with measurable disease parameters according to the International Myeloma Working Group (IMWG) Criteria
- Refractory is defined as experiencing less than minimal response (MR) to or progressive disease (PD) within 60 days after completion of the most recent anti-MM regimen
- Relapsed is defined as experiencing PD that requires therapy but which is not refractory following the achievement of stable disease (SD) or better to the most recent anti-MM regimen.
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Patient received at least 2 prior regimens for MM.
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Patient received prior treatment for MM with a proteasome inhibitor and an immunomodulatory drug, unless not a candidate for a proteasome inhibitor or an immunomodulatory drug.
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Patient either is not a candidate for autologous stem cell transplant (ASCT), has declined the option of ASCT, or has relapsed after prior ASCT.
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Patient is ≥18 years of age.
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Patient has a Karnofsky Performance Status score of ≥70
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Patient has adequate bone marrow reserve, as evidenced by:
- Absolute neutrophil count (ANC) of ≥1.0x109/L.
- Platelet count of ≥ 75x109/L in patients in whom <50% of bone marrow nucleated cells are plasma cells and ≥50x109/L in patients in whom more than 50% of bone marrow nucleated cells are plasma cells.
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Patient has adequate renal function (calculated creatinine clearance of ≥30 mL/min according to the Cockroft-Gault)
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Patient has adequate hepatic function (serum bilirubin values <2.0 mg/dL and ALT and/or AST values <3 × the upper limit of normal ULN).
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Patient has a corrected serum calcium ≤ULN.
Exclusion Criteria
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Patient has received any of the following therapies:
- Radiotherapy or systemic therapy within 2 weeks of baseline
- Prior peripheral autologous stem cell transplant within 12 wks of Baseline.
- Prior allogeneic stem cell transplant.
- Prior treatment with an HDAC inhibitor.
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Patient has an active systemic infection requiring treatment.
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Patient has a history of other malignancies unless has undergone definitive treatment more than 5 yrs prior to study and without evidence of recurrent malignant disease (excluding basal cell carcinoma of the skin; superficial carcinoma of the bladder; carcinoma of the prostate with a current prostate-specific antigen <0.1 ng/mL; or cervical intraepithelial neoplasia).
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Patient has known or suspected HIV, positive for hepatitis B or is known or suspected to have active hepatitis C infection.
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Patient has a history of significant cardiovascular, neurological, endocrine, gastrointestinal, respiratory, or inflammatory illness including recent myocardial infarction (within 6 months)or stroke; hypertension requiring >2 medications for adequate control; diabetes mellitus with >2 episodes of ketoacidosis in the preceding 12 months; or chronic obstructive pulmonary disease (COPD) requiring >2 hospitalizations in the preceding 12 months.
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Patient has a QTcF value of >480 msec; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy; previous history of drug-induced QTc prolongation
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Patient has > Grade 2 painful neuropathy or peripheral neuropathy
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Patient has a history of allergic reaction attributable to bortezomib or other compounds containing boron or mannitol (Phase 1b and 2a only)
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treat Regimen ACY-1215 ACY-1215 Bortezomib Dexamethasone
- Primary Outcome Measures
Name Time Method Phase 1 (a & b): To determine the maximum tolerated dose of ACY-1215 as monotherapy or in combination with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma. Upon completion of 21-day treatment cycle Phase 2a: To determine the objective response rate to ACY-1215 in combination with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma. Assessed every other treatment cycle (cycles 2, 4 and 6)
- Secondary Outcome Measures
Name Time Method Determine the single- and multiple-dose PK of ACY-1215 alone and in combination with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma Upon completion of 21 day treatment cycle Characterize the safety of ACY-1215 alone or in combination with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma Up to 24 weeks Evaluate the pharmacodynamics of ACY-1215 alone or in combination with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma. Up to 24 weeks.
Trial Locations
- Locations (6)
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Winship Cancer Institute, Emory University
🇺🇸Atlanta, Georgia, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Medical College of Wisconsin - Clinical Cancer Center
🇺🇸Milwaukee, Wisconsin, United States
Mt. Sinai Medical Center
🇺🇸New York, New York, United States