Study of ACY-1215 Alone and in Combination With Bortezomib and Dexamethasone in Multiple Myeloma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treat Regimen ACY-1215 Bortezomib Dexamethasone |
Drug: ACY-1215
Liquid oral dose on Days 1-5 and 8-12 of 21-day treatment cycle
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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]
- 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]
- 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.]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patient has relapsed or relapsed/refractory MM with measurable disease parameters according to the International Myeloma Working Group (IMWG) Criteria
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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
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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:
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Absolute neutrophil count (ANC) of ≥1.0x109/L.
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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:
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Radiotherapy or systemic therapy within 2 weeks of baseline
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Prior peripheral autologous stem cell transplant within 12 wks of Baseline.
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Prior allogeneic stem cell transplant.
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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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Winship Cancer Institute, Emory University | Atlanta | Georgia | United States | 30322 |
| 2 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02115 |
| 3 | Mt. Sinai Medical Center | New York | New York | United States | 10029 |
| 4 | University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
| 5 | MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 6 | Medical College of Wisconsin - Clinical Cancer Center | Milwaukee | Wisconsin | United States | 53226 |
Sponsors and Collaborators
- Celgene
- The Leukemia and Lymphoma Society
Investigators
- Principal Investigator: Sagar Lonial, MD, Winship Cancer Institute, Emory University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ACY-100