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

NCT01323751 | Completed Phase 1 DMC

• 1 other identifier: ACY-100
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 6

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• 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.

Study Arms (1)

Treat Regimen

EXPERIMENTAL

ACY-1215 Bortezomib Dexamethasone

Drug: ACY-1215

Interventions

ACY-1215 DRUG

Liquid oral dose on Days 1-5 and 8-12 of 21-day treatment cycle

Also known as: HDAC6 inhibitor

Treat Regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Celgene: lead
• The Leukemia and Lymphoma Society: collaborator

Study Sites (6)

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

Mt. Sinai Medical Center

New York, New York, 10029, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Medical College of Wisconsin - Clinical Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ricolinostat

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Sagar Lonial, MD

  Winship Cancer Institute, Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2011
• First Posted: March 28, 2011
• Study Start: July 1, 2011
• Primary Completion: December 1, 2016
• Study Completion: December 3, 2016
• Last Updated: April 6, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will share

Locations

US (6)