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

This study is ongoing, but not recruiting participants.
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: April 13, 2016
Last verified: December 2015
  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: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: HDAC6 inhibitor

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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

Locations
United States, Georgia
Winship Cancer Institute, Emory University
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02115
United States, New York
Mt. Sinai Medical Center
New York, New York, United States, 10029
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Wisconsin
Medical College of Wisconsin - Clinical Cancer Center
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Acetylon Pharmaceuticals Incorporated
The Leukemia and Lymphoma Society
Investigators
Principal Investigator: Sagar Lonial, MD Winship Cancer Institute, Emory University
  More Information

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: April 13, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: Yes

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

ClinicalTrials.gov processed this record on December 02, 2016