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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Acetylon Pharmaceuticals Incorporated
Sponsor:
Collaborator:
The Leukemia and Lymphoma Society
Information provided by (Responsible Party):
Acetylon Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT01323751
First received: February 25, 2011
Last updated: September 15, 2014
Last verified: September 2014
  Purpose

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 Intervention Phase
Multiple Myeloma
Drug: ACY-1215
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Acetylon Pharmaceuticals Incorporated:

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. [ Time Frame: Upon completion of 21-day treatment cycle ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: Assessed every other treatment cycle (cycles 2, 4 and 6) ] [ Designated as safety issue: Yes ]

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 [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: Upon completion of 21 day treatment cycle ] [ Designated as safety issue: No ]
  • Evaluate the pharmacodynamics of ACY-1215 alone or in combination with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma. [ Time Frame: Up to 24 weeks. ] [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: July 2011
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: ACY-1215
    Liquid oral dose on Days 1-5 and 8-12 of 21-day treatment cycle
    Other Name: HDAC6 inhibitor
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01323751

Contacts
Contact: Gina Leone 617-245-1300 gleone@acetylon.com

Locations
United States, Georgia
Winship Cancer Institute, Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Jennifer Schreiber Merriweather, RN    404-778-5920    jennifer.schreiber@emoryhealthcare.org   
Principal Investigator: Sagar Lonial, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Chi La    617-724-5251    cla@partners.org   
Principal Investigator: Noopur Raje, MD         
United States, New York
Mt. Sinai Medical Center Recruiting
New York, New York, United States, 10029
Contact: Kenneth Lau    212-241-7846    kenneth.lau@mssm.edu   
Contact: Lisa La    212-241-8615    lisala@mssm.edu   
Principal Investigator: Sundar Jagganath, MD         
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Kristy Walsh    215-615-4822    kristy.walsh@uphs.upenn.edu   
Principal Investigator: Dan Vogl, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Martha Anderson, RN    713-794-1079    mlanderson1@mdanderson.org   
Principal Investigator: Robert Z Orlowski, PhD, MD         
United States, Wisconsin
Medical College of Wisconsin - Clinical Cancer Center Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Paulette Jacobs    414-805-4594    pjacobs@mcw.edu   
Principal Investigator: Parameswaran Hari, M.D.         
Sponsors and Collaborators
Acetylon Pharmaceuticals Incorporated
The Leukemia and Lymphoma Society
Investigators
Principal Investigator: Sagar Lonial, MD Winship Cancer Institute, Emory University
  More Information

No publications provided

Responsible Party: Acetylon Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT01323751     History of Changes
Other Study ID Numbers: ACY-100
Study First Received: February 25, 2011
Last Updated: September 15, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 23, 2014