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Study of ACY-1215 in Combination With Lenalidomide, and Dexamethasone in Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Acetylon Pharmaceuticals Incorporated
Sponsor:
Information provided by (Responsible Party):
Acetylon Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT01583283
First received: April 11, 2012
Last updated: January 27, 2014
Last verified: January 2014
  Purpose

The purpose of this study is to determine the best dose of ACY-1215 in combination with lenalidomide and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma. Once determined, the purpose of this study will be to determine the efficacy of ACY-1215 in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma who have had 1-3 prior therapies and who are not lenalidomide-refractory.


Condition Intervention Phase
Multiple Myeloma
Drug: ACY-1215
Drug: lenalidomide
Drug: Dexamethasone
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 I/II, Open Label, Multicenter Study of ACY-1215 in Combination With Lenalidomide 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:
  • Establish optimal dose of ACY-1215 in combination with lenalidomide and dexamethasone [ Time Frame: Upon completion of a 28 day treatment cycle ] [ Designated as safety issue: Yes ]

    Determine maximum tolerated dose (MTD) of combination therapy. Patients will be assessed for dose-limiting toxicities (DLT) at each visit during Cycle 1.

    During the second part of the study, investigate efficacy of the dose determined during the first part of the study by objective response rate and progression-free survival.



Secondary Outcome Measures:
  • Evaluate safety by assessing toxicities [ Time Frame: Upon completion of a 28 day treatment cycle ] [ Designated as safety issue: Yes ]
    Evaluate safety by assessing possible toxicities of thrombocytopenia, neutropenia, serum creatinine, total bilirubin, diarrhea, and/or vomiting.

  • Determine the preliminary anti-tumor activity of ACY-1215 in combination with lenalidomide and dexamethasone [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: Yes ]
    Change in M-protein (baseline to the end of each 28 day cycle, up to 24 weeks), objective response rate assessed according to the IMWG criteria (baseline, every other day 15 of each cycle, up to 24 weeks).

  • Area under the plasma concentration versus time curve (AUC) [ Time Frame: Upon completion of a 28 day cycle. ] [ Designated as safety issue: No ]
    AUC of ACY-1215 and lenalidomide

  • Changes in acetylated tubulin and acetylated histone levels [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]
    Evaluation of changes in acetylated tubulin(blood and bone marrow)and acetylated histones (blood and bone marrow)at baseline and post-treatment (Day 1 and up to week 24)


Estimated Enrollment: 148
Study Start Date: April 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ACY-1215, Lenalidomide and dexamethasone
Open label dosing cohorts will evaluate oral ACY-1215 (doses ranging from 40 - 480 mg days 1-5, 8-12, 15-19) in combination with oral Lenalidomide (doses ranging from 15 - 25 mg days 1-21) and oral dexamethasone (40 mg once weekly).
Drug: ACY-1215
Dose escalation up to 480 mg administered orally on Days 1-5, 8-12 and 15-19 of a 28 day dosing schedule.
Other Name: Histone deacetylase inhibitor
Drug: lenalidomide
Dosed on Days 1-21 of a 28 day cycle.
Other Name: Revlimid
Drug: Dexamethasone
Dosed on Days 1, 8, 15 and 22 of a 28 day treatment cycle.
Other Name: steroid

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Relapsed or Relapsed/Refractory MM with progressive disease (PD) according to IMWG.
  • Received at least 1 prior line of therapy for MM (Phase 1)
  • Secretory MM for which the patient previously received 1-3 prior lines of therapy (Phase 2).
  • Able to provide written consent
  • Not a candidate for autologous stem cell transplant (ASCT) or declined option.
  • ≥18 years of age
  • Karnofsky Performance Status score ≥ 70
  • Adequate bone marrow reserve as evidenced by ANC > 1.0x10^9/L;Platelet > 50x10^9/L
  • Creatinine Clearance of ≥ 50 mL/min
  • Adequate hepatic function as evidenced by serum bilirubin values < 2.0 mg/dL; ALT and/or AST < 3xULN.
  • Corrected serum calcium ≤ ULN
  • Recovered from the effects of any prior systemic therapy or radiotherapy for Multiple Myeloma
  • Able to take acetylsalicylic acid (ASA) (81 or 325 mg) daily as prophylactic anticoagulation. Patients intolerant to ASA may use low molecular weight heparin. Lovenox is recommended. Coumadin will be allowed provided the patient is fully anticoagulated, with an INR of 2 or 3.
  • Agreement to participate in RevAssist® Program
  • Female of childbearing potential must have a negative serum or urinary pregnancy test with a sensitivity of at least 50 mIU/mL 10-14 days prior to and again within 24 hours of prescribing lenalidomide for Cycle 1 and must either commit to continued abstinence or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method at the same time, at least 28 days prior to taking lenalidomide. Also agree to ongoing pregnancy testing.
  • If male, including those who have had a vasectomy, must agree to use a latex condom during any sexual contact with a female of childbearing potential.

Exclusion Criteria:

  • Received any of the following antitumor therapies

    • Radiotherapy or systemic therapy within 2 weeks of Cycle 1 Day 1 (C1D1)
    • Investigational or biologic therapies within 3 weeks of C1D1
    • Prior peripheral ASCT within 12 weeks of C1D1
    • Prior allogeneic stem cell transplant
    • Prior treatment with a histone deacetylase (HDAC) inhibitor
  • Presence of an active systemic infection requiring treatment.
  • History of other malignancies unless a.) the patient has undergone definitive treatment more than 5 years prior and is without evidence of recurrent malignant disease or b.) had basal or squamous cell carcinoma of the skin; superficial carcinoma of the bladder; carcinoma of the prostate with current prostat specific antigen < 0.1 ng/mL; ductal carcinoma in situ; or cervical intraepithelial neoplasia.
  • Known or suspected human immunodeficiency virus (HIV), hepatitis B surface antigen-positive status or known or suspected active hepatitis C infection.
  • If female, is lactating.
  • History of significant cardiovascular, neurological, endocrine, gastrointestinal, respiratory, or inflammatory illness that could preclude study participation, pose an undue medical hazard, or interfere with the interpretation of the study results, including but not limited to congestive heart failure (NYHA Class 3 or 4), unstable angina; cardiac arrhythmia, recent (within past 6 months) myocardial infarction or stroke; uncontrolled hypertension; diabetes mellitus with >2 episodes of ketoacidosis in the preceding 12 months, COPD requiring >2 hospitalizations in preceding 12 months
  • QTcF > 480 msec, family or personal history of long QTc syndrome or ventricular bigeminy; previous history of drug-induced QTc prolongation or the need for medications known or suspected of producing prolonged QTc intervals on ECG
  • Current enrollment in another clinical trial involving treatment and/or is receiving an investigational agent for any reason
  • Documented plasma cell leukemia or known amyloidosis. (Plasma cell leukemia is defined as the presence of >20% plasma cells in the peripheral blood and an absolute plasma cell count of ≥2000 muL
  • Known hypersensitivity to thalidomide or lenalidomide.
  • History of erythema nodosum characterized by desquamating rash while taking thalidomide or similar drugs.
  • Non-secretory or oligo-secretory Multiple Myeloma (Phase II only; such disease is permissible in Phase I).
  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: NCT01583283

Contacts
Contact: Gretchen Patrick 617-245-1319 gpatrick@acetylon.com

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Nicole Couture    617-724-2689    ncouture@partners.org   
Principal Investigator: Andrew Yee, MD         
United States, North Carolina
UNC Lineberger Comprehensive Cancer Center Recruiting
Chapel Hill, North Carolina, United States, 27599-7305
Contact: Elizabeth Tita, RN, BSN    919-843-7657    elizabeth_tita@med.unc.edu   
Principal Investigator: Peter Voorhees, MD         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Cindy Farley    615-329-7237    cindy.farley@scresearch.net   
Principal Investigator: Jesus Berdeja, MD         
United States, Washington
Fred Hutchinson Cancer Research Institute Recruiting
Seattle, Washington, United States, 98109
Contact: Cari Morin    206-667-6238    cmorin@fhcrc.org   
Principal Investigator: William Bensinger, MD         
Sponsors and Collaborators
Acetylon Pharmaceuticals Incorporated
Investigators
Principal Investigator: Noopur Raje, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Acetylon Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT01583283     History of Changes
Other Study ID Numbers: ACE-MM-101
Study First Received: April 11, 2012
Last Updated: January 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Acetylon Pharmaceuticals Incorporated:
Multiple Myeloma
Relapsed
Refractory
Histone deacetylase inhibitors
Lenalidomide
Revlimid
Dexamethasone

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
Histone Deacetylase Inhibitors
Lenalidomide
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents

ClinicalTrials.gov processed this record on November 24, 2014