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ACY-1215 (Ricolinostat) in Combination With Pomalidomide and Low-dose Dex in Relapsed-and-Refractory Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Acetylon Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT01997840
First received: November 20, 2013
Last updated: October 17, 2016
Last verified: October 2016
  Purpose

Phase 1b: To evaluate the side effects and determine the best dose of ACY-1215 in combination with Pomalidomide and low-dose dexamethasone in patients with relapsed-and-refractory multiple myeloma.

Phase 2: To determine the overall response rate of ACY-1215 in combination with Pomolidomide and low-dose dexamethasone in patients with relapsed-and-refractory multiple myeloma


Condition Intervention Phase
Multiple Myeloma
Drug: ACY-1215 (Ricolinostat) in combination with pomalidomide and 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 1b/2 Multicenter, Open Label, Dose-Escalation Study to Determine the Maximum Tolerated Dose, Safety, and Efficacy of ACY-1215 (Ricolinostat) in Combination With Pomalidomide and Dex in Patients With Relapsed-and-Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Acetylon Pharmaceuticals Incorporated:

Primary Outcome Measures:
  • Phase 1b: MTD and dosing schedule of ACY-1215 administered in combination with pomalidomide and low-dose dexamethasone in patients with MM [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Phase 2: Overall response rate of ACY-1215 in combination with pomalidomide and dexamethasone in patients with relapsed-and-refractory multiple myeloma [ Time Frame: Every 56 days for the duration on treatment, an estimated average of 4 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Phase 1b & 2: Safety assessed by type, frequency and severity of AEs and relationship of AEs to study drug [ Time Frame: Upon completion of a 28 day treatment cycle and for the duration of treatment, an estimated average of 4 months. ] [ Designated as safety issue: Yes ]
  • Phase 1b and 2: Efficacy assessed by time to response, duration of response, time to progression, progression free survival, and objective response as assessed by a central adjudication committee [ Time Frame: Every 56 days on treatment, estimated average of 4 months. Survival will be evaluated every 4 months for up to 5 years. ] [ Designated as safety issue: Yes ]
  • Phase 1b: Plasma levels of ACY-1215 and plasma levels of pomalidomide [ Time Frame: Up to 8 days post first dose ] [ Designated as safety issue: Yes ]
  • Phase 1b: Exposure response of treatment including biomarkers relating to intracellular protein acetylation, protein levels, mRNA and microRA expression profiles. [ Time Frame: Up to 24 hours post first dose ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • Phase 2: Relationship between response to treatment and any cytogenetic abnormalities [ Time Frame: Duration on study, estimated average of 4 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: November 2013
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ACY-1215 in combination with pomalidomide and dexamethasone
ACY-1215 (Ricolinostat) in combination with pomalidomide and dexamethasone
Drug: ACY-1215 (Ricolinostat) in combination with pomalidomide and dexamethasone
ACY-1215 (Ricolinostat) 160mg QD Days 1-21 with pomalidomide 4mg QD Days 1-21 and dexamethasone 40mg QD Days 1,8,15,22 of a 28-day cycle
Other Names:
  • Pomalyst
  • Ricolinostat
  • Dexamethasone

  Eligibility

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

Inclusion Criteria:

  • Must have a documented diagnosis of multiple myeloma and have relapsed-and-refractory disease. Patients must have received at least 2 lines of prior therapies. Patients must have relapsed after having achieved at least stable disease (SD) for at least one cycle of treatment to at least one prior regimen and then developed progressive disease (PD). Patients must also have documented evidence of PD during or within 60 days (measured from the end of the last cycle) of completing treatment with the last anti-myeloma drug regimen used just prior to study entry (refractory disease)
  • Must have undergone prior treatment with at least 2 cycles of lenalidomide and at least 2 cycles of a proteasome inhibitor (either in separate regimens or within the same regimen)
  • Must not be a candidate for autologous stem cell transplant (ASCT), has declined the option of ASCT, or has relapsed after prior ASCT
  • Must have measurable levels of myeloma paraprotein in serum (≥ 0.5 g/dL) or urine (≥ 0.2 g/24 hours)
  • Must have Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
  • Females of child bearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to, and again within 24 hours of starting pomalidomide and must either commit to continued abstinence from heterosexual intercourse 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 before she starts taking pomalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods,and Education and Counseling Guidance must be followed per protocol
  • Must be 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 international normalized ratio (INR) of 2 to 3

Exclusion Criteria:

  • Pregnant or lactating females
  • Prior therapy with HDAC inhibitor
  • Any of the following laboratory abnormalities:

    • ANC < 1,000/µL
    • Platelet count < 75,000/ µL for patients in whom < 50% of bone marrow nucleated cells are plasma cells; and < 50,000/ µL for patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells
    • Hemoglobin < 8g/dL (<4.9 mmol/L; prior red blood cell [RBC] transfusion is permitted)
    • Creatine clearance < 45mL/min according to Cockcroft-Gault formula. If creatine clearance calculated from the 24-hour urine sample is ≥ 45 mL/min, patient will qualify for the study
    • Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST), or serum glutamic pyruvic transaminase (SGPT)/ alanine aminotransferase (ALT) > 3.0 × ULN
    • Serum total bilirubin > 2.0 mg/dL
  • Prior history of malignancies, other than MM, unless the patient has been free of the disease for ≥ 3 years. Exceptions include the following:

    • Basal or squamous cell carcinoma of the skin
    • Carcinoma in situ of the cervix or breast
    • Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)
  • Corrected QT interval using Fridericia's formula (QTcF) value > 480 msec at screening; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy; previous history of drug-induced QTc prolongation or the need for treatment with medications known or suspected of producing prolonged QTc intervals on electrocardiogram (ECG)
  • Positive human immunodeficiency virus (HIV), hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection
  • Hypersensitivity to thalidomide, lenalidomide, or dexamethasone (such as Steven Johnson Syndrome). Hypersensitivity, such as rash, that can be medically managed is allowable
  • Peripheral neuropathy ≥ Grade 2 despite supportive therapy
  • Radiotherapy or systemic therapy (standard or an investigational or biologic anticancer agent) within 14 days of initiation of study drug treatment
  • Current enrollment in another clinical trial involving treatment and/or is receiving an investigational agent for any reason
  • Inability or unwillingness to comply with birth control requirements or regional REMS/RevAid programs
  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: NCT01997840

Locations
United States, Georgia
Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Washington University School of Medicine at St. Louis
St. Louis, Missouri, United States, 63110
United States, New York
New York Medical College
Hawthorne, New York, United States, 10512
New York Medical College
Hawthorne, New York, United States, 10532
Mt. Sinai Medical Center
New York, New York, United States, 10029
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Ohio State University, James Cancer Hospital
Columbus, Ohio, United States, 43210
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
Fred Hutchinson Cancer Research Institute
Seattle, Washington, United States, 98109
United States, Wisconsin
Medical College of Wisconsin - Clinical Cancer Center
Milwaukee, Wisconsin, United States, 53226
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Canada, Alberta
Tom Baker Cancer Center
Calgary, Alberta, Canada, T2N 4N2
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 2M9
Greece
"University of Athens school of Medicine"
Athens, Greece
Italy
A.O.U. Citta della Salute e della Scienza di Torino/Hematology
Torino, Italy
Sponsors and Collaborators
Acetylon Pharmaceuticals Incorporated
Investigators
Principal Investigator: Noopur Raje, MD Massachusetts General Hospital
  More Information

Responsible Party: Acetylon Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT01997840     History of Changes
Other Study ID Numbers: ACE-MM-102 
Study First Received: November 20, 2013
Last Updated: October 17, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Acetylon Pharmaceuticals Incorporated:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Blood Protein Disorders
Hematologic Diseases
Dexamethasone
Dexamethasone acetate
Pomalidomide

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
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

ClinicalTrials.gov processed this record on December 07, 2016