Study of ACY-1215 Alone and in Combination With Bortezomib and Dexamethasone in Multiple Myeloma

Celgene

Status and phase

Completed

Phase 2

Phase 1

Conditions

Multiple Myeloma

Treatments

Drug: ACY-1215

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01323751

ACY-100

Details and patient eligibility

About

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.

Enrollment

120 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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)