Multiple Myeloma
Conditions
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.
Interventions
DRUGACY-1215
Liquid oral dose on Days 1-5 and 8-12 of 21-day treatment cycle
Sponsors
The Leukemia and Lymphoma Society
Celgene
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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. * Patient received at least 2 prior regimens for MM. * 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. * Patient either is not a candidate for autologous stem cell transplant (ASCT), has declined the option of ASCT, or has relapsed after prior ASCT. * Patient is ≥18 years of age. * Patient has a Karnofsky Performance Status score of ≥70 * 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. * Patient has adequate renal function (calculated creatinine clearance of ≥30 mL/min according to the Cockroft-Gault) * 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). * Patient has a corrected serum calcium ≤ULN.
Exclusion criteria
* 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. * Patient has an active systemic infection requiring treatment. * 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). * Patient has known or suspected HIV, positive for hepatitis B or is known or suspected to have active hepatitis C infection. * 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. * 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 * Patient has \> Grade 2 painful neuropathy or peripheral neuropathy * Patient has a history of allergic reaction attributable to bortezomib or other compounds containing boron or mannitol (Phase 1b and 2a only)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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. |
Countries
United States
Outcome results
None listed