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Study of ACY-241 Alone and in Combination With Pomalidomide and Dexamethasone in Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2016 by Acetylon Pharmaceuticals Incorporated
Sponsor:
Information provided by (Responsible Party):
Acetylon Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT02400242
First received: March 3, 2015
Last updated: October 12, 2016
Last verified: October 2016
  Purpose
This is a phase 1a/1b, multicenter, single-arm, open-label, dose escalation study to determine the maximum tolerated dose (MTD) and evaluate the safety and preliminary antitumor activity of ACY-241 for oral administration as monotherapy and in combination therapy with orally administered pomalidomide and low-dose dexamethasone in eligible patients with relapsed or relapsed-and-refractory multiple myeloma (MM).

Condition Intervention Phase
Multiple Myeloma
Drug: ACY-241
Drug: Pomalidomide
Drug: Dexamethasone
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Dose-Escalation Study to Determine the Maximum Tolerated Dose, Safety, and Preliminary Antitumor Activity of Oral ACY-241 Alone and in Combination With Pomalidomide and Low Dose Dexamethasone in Relapsed or Relapsed and Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Acetylon Pharmaceuticals Incorporated:

Primary Outcome Measures:
  • Maximum tolerated dose of ACY-241 as monotherapy as assessed by dose limiting toxicities [ Time Frame: Cycle 1 (28 days) ]
  • Maximum tolerated dose of ACY-241 in combination with pomalidomide and low dose dexamethasone as assessed by dose limiting toxicities [ Time Frame: Cycle 2 (28 days) ]
    First cycle of combination therapy


Secondary Outcome Measures:
  • Frequency and severity of AEs as measured by safety and tolerability [ Time Frame: Cycle 1 (28 days) ]
  • Single- and multiple-dose peak-plasma concentration [ Time Frame: Cycle 1 days 1, 2, 15 and 16 ]
  • Single- and multiple-dose area under the plasma concentration versus time curve [ Time Frame: Cycle 1 days 1, 2, 15 and 16 ]
  • Change in acetylation of histone and tubulin as a measure of pharmacodynamics [ Time Frame: Cycles 1 days 1, 2, 15, 16 and 22 ]
  • Change in fetal hemoglobin expression as a measure of pharmacodynamics [ Time Frame: Cycles 1 days 1, 2, 15, 16 and 22 ]
  • ACY-241 metabolite concentration in blood samples [ Time Frame: Cycles 1 days 1, 2, 15, 16 and 22 ]
  • Exposure response analyses of potential biomarkers of response. [ Time Frame: Cycles 1 days 1, 2, 15, 16 and 22 ]
  • Frequency and severity of AEs as measured by safety and tolerability in combination [ Time Frame: Beginning at Cycle 2 (28 day cycle each) until end of treatment ]
  • Change in fetal hemoglobin expression as a measure of pharmacodynamics [ Time Frame: Cycle 2 days 1, 2, 15, 16 and 22 ]
  • Change in acetylation of histone and tubulin as a measure of pharmacodynamics [ Time Frame: Cycle 2 days 1, 2, 15, 16 and 22 ]
  • Single- and multiple-dose area under the plasma concentration versus time curve [ Time Frame: Cycle 2 days 1, 2, 15, and 16 ]
  • Quantification of M-protein as a measure of anti-tumor activity [ Time Frame: Day 1 of each cycle beginning at Cycle 2 ]

Estimated Enrollment: 115
Study Start Date: April 2015
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ACY-241, Pomalidomide, and dexamethasone
Open label dosing cohorts will evaluate oral ACY-241 (dosing ranging from 180 mg to 480 mg days 1-21) in combination with oral pomalidomide (4 mg days 1-21), and oral dexamethasone (40 mg qd on days 1, 8, 15, 22).
Drug: ACY-241
Dose escalation up to 480 mg administered orally on Days 1-21 of a 28 day cycle.
Other Name: Histone deacetylase inhibitor
Drug: Pomalidomide
4 mg qd dosed on days 1-21 of a 28 day cycle
Other Name: immunomodulatory agent
Drug: Dexamethasone
40 mg qd on days 1, 8, 15, 22
Other Name: corticosteriod

Detailed Description:
During phase 1a, patients will receive 1 cycle of ACY-241 monotherapy. Patients who complete the ACY-241 monotherapy cycle without a dose limiting toxicity (DLT) and are clinically stable may continue to phase 1b combination therapy, beginning with Cycle 2. During phase 1b, patients will receive ACY 241 in combination with pomalidomide and low dose dexamethasone at the currently approved pomalidomide dose and schedule. Each cohort of patients in phase 1a and phase 1b will consist of at least 3 patients. The first patient enrolled in each cohort of phase 1a will be observed for 1 week before enrollment of subsequent patients in the cohort. Patients who withdraw consent before entering phase 1b will be replaced. (Replacement patients must complete phase 1a prior to continuing to phase 1b.) Patients who experience a DLT or other unacceptable toxicity in Cycle 1 of phase 1a monotherapy or Cycle 2, the first cycle of phase 1b combination therapy, will be removed from study treatment. An assessment of the safety of treatment will be completed by the Safety Review Committee (SRC) prior to dose-escalation.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Must have a documented diagnosis of MM and have relapsed or relapsed-and-refractory disease. All patients must have relapsed after having achieved at least stable disease (SD) for at least 1 cycle of treatment to at least 1 prior regimen and then developed progressive disease (PD). Relapsed-and-refractory patients also have documented evidence of PD during or within 60 days of completing last treatment
  • Must have undergone prior treatment with at least 2 cycles of lenalidomide and at least 2 cycles of proteasome inhibitor unless not a candidate.
  • May have undergone prior treatment with pomalidomide if patient is not refractory to pomalidomide and has previously achieved a response of MR or better to pomalidomide.
  • Must have measurable disease (serum M-protein or urine M-protein).
  • Must have Eastern Cooperative Oncology Group (ECOG) Performance score of 0, 1, or 2.
  • Must be able to take low-dose aspirin, low molecular weight heparin, or other equivalent antithrombotic or anticoagulant daily as prophylactic anticoagulation.

Key Exclusion Criteria:

  • Prior therapy with pomalidomide with best response of PD or SD.
  • Prior therapy with histone deacetylase (HDAC) inhibitor.
  • Any of the following laboratory abnormalities: Absolute neutrophil count(ANC) < 1,000/µL, Platelet count < 75,000/µL or < 50,000/µL for patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells, Hemoglobin < 8 g/dL, Creatinine clearance < 45 mL/min according to Cockcroft-Gault formula. If creatinine clearance calculated from the 24 hour urine sample is ≥ 45 mL/min, patient will qualify for the trial, Aspartate transaminase (AST) or Alanine transaminase (ALT) > 3.0 × Upper Limited Normal (ULN), Serum total bilirubin > 2.0 mg/dL or > 3.0 × ULN for patients with hereditary benign hyperbilirubinaemia.
  • Hematologic growth factors are not allowed at screening or during the first cycle of phase 1a or 1b.
  • Nonsecretory myeloma or free light chain detected in serum only (ogliosecretory).
  • Hypersensitivity to thalidomide, lenalidomide, pomalidomide, or dexamethasone
  • Patients who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant less than 12 months prior to initiation of study
  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: NCT02400242

Contacts
Contact: Lisa M Smith 617-245-1332 lsmith@acetylon.com
Contact: Robert Markelewicz, MD rmarkelewicz@acetylon.com

Locations
United States, Arizona
University of Arizona Recruiting
Tucson, Arizona, United States, 8719
Principal Investigator: Amit Agarwal, MD, PhD         
United States, Colorado
Colorado Blood Instittute Recruiting
Denver, Colorado, United States, 80218
Principal Investigator: Jeffrey Matous, MD         
United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Principal Investigator: James Hoffman, MD         
United States, Georgia
Emory University Winship Cancer Center Recruiting
Atlanta, Georgia, United States, 30322
Principal Investigator: Nooka Anjay, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Principal Investigator: Noopur Raj, MD         
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Sub-Investigator: Paul Richardson, MD         
United States, New York
Weill Cornell Medical College Recruiting
New York, New York, United States, 10065
Principal Investigator: Rueben Niesvizky, MD         
United States, Ohio
Gabrail Cancer Center Recruiting
Canton, Ohio, United States, 44718
Principal Investigator: Nashat Gabrail, MD         
United States, Washington
Swedish Cancer Center Recruiting
Seattle, Washington, United States, 98104
Principal Investigator: John Pagel, MD         
France
CHRU de Lille - Hôpital Claude Huriez Recruiting
Lille, France
Principal Investigator: Thierry Facon, MD         
University Hospital Hôtel-Dieu Recruiting
Nantes, France
Principal Investigator: Philippe Moreau, MD         
Germany
Medizinische Klinik, Abt. Innere Medizin V Recruiting
Heidelberg, Germany, 69120
Principal Investigator: Marc-Steffen Raab, MD         
Greece
University of Athens School of Medicine Recruiting
Athens, Greece, 11528
Principal Investigator: Evangelos Terpos, MD         
Ireland
Mater Misericordiae University Hospital and Mater Private Hospital Not yet recruiting
Dublin, Ireland
Principal Investigator: Peter O'Gorman         
Spain
Clinica Universidad de Navarra Recruiting
Navarra, Spain
Principal Investigator: Jesus San Miguel, MD         
Hospital Universitario Salamanca Recruiting
Salamanca, Spain, 37007
Principal Investigator: Maria Victoria Mateos Manteca, MD         
Sponsors and Collaborators
Acetylon Pharmaceuticals Incorporated
Investigators
Principal Investigator: Ruben Niesvizky, MD Weill Medical College of Cornell University
  More Information

Responsible Party: Acetylon Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT02400242     History of Changes
Other Study ID Numbers: ACE-MM-200
Study First Received: March 3, 2015
Last Updated: October 12, 2016

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
Pomalidomide
Thalidomide
BB 1101
Histone Deacetylase Inhibitors
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on March 29, 2017