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

A Phase 1/2, Open-Label, Multicenter Study of ACY-1215 Administered Orally as Monotherapy and in Combination With Bortezomib and Dexamethasone for the Treatment of Relapsed or Relapsed/Refractory Multiple Myeloma

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: ACY-1215

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute, Emory University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Massachusetts General Hospital
  • New York
    • New York, New York, United States, 10029
      • Mt. Sinai Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin - Clinical Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: HDAC6 inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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.

Collaborators and Investigators

• Sponsor: Celgene
• Collaborators: The Leukemia and Lymphoma Society
• Investigators: Principal Investigator: Sagar Lonial, MD, Winship Cancer Institute, Emory University

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 3, 2016

Study Registration Dates

• First Submitted: February 25, 2011
• First Submitted That Met QC Criteria: March 25, 2011
• First Posted (Estimate): March 28, 2011

Study Record Updates

• Last Update Posted (Actual): April 6, 2017
• Last Update Submitted That Met QC Criteria: April 5, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Histone Deacetylase Inhibitors; Ricolinostat
• Other Study ID Numbers: ACY-100

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES