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

Sponsor

Celgene (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT01997840

Collaborator

(none)

103

Enrollment

Locations

Arm

112

Anticipated Duration (Months)

4.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: ACY-1215 (Ricolinostat) in combination with pomalidomide and dexamethasone	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

103 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1B/2 Multi-Center, Open Label, Dose-Escalation Study to Determine the Maximum Tolerated Dose, Safety, and Efficacy of ACY-1215 (RICOLINOSTAT) in Combination With Pomalidomide and Low-Dose Dexamethasone in Patients With Relapsed and Refractory Multiple Myeloma

Actual Study Start Date :

Mar 1, 2014

Anticipated Primary Completion Date :

Jun 30, 2023

Anticipated Study Completion Date :

Jun 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

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 [28 days]
Phase 2: Overall response rate of ACY-1215 in combination with pomalidomide and dexamethasone in patients with relapsed-and-refractory multiple myeloma [Every 56 days for the duration on treatment, an estimated average of 4 months]

Secondary Outcome Measures

Phase 1b & 2: Safety assessed by type, frequency and severity of AEs and relationship of AEs to study drug [Upon completion of a 28 day treatment cycle and for the duration of treatment, an estimated average of 4 months.]
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 [Every 56 days on treatment, estimated average of 4 months. Survival will be evaluated every 4 months for up to 5 years.]
Phase 1b: Plasma levels of ACY-1215 and plasma levels of pomalidomide [Up to 8 days post first dose]
Phase 1b: Exposure response of treatment including biomarkers relating to intracellular protein acetylation, protein levels, mRNA and microRA expression profiles. [Up to 24 hours post first dose]

Other Outcome Measures

Phase 2: Relationship between response to treatment and any cytogenetic abnormalities [Duration on study, estimated average of 4 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
2	Horizon Oncology Center	Lafayette	Indiana	United States	47905
3	Local Institution - 207	Lafayette	Indiana	United States	47905
4	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
5	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
6	Univesity of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0922
7	Local Institution - 209	Saint Louis	Missouri	United States	63110
8	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
9	Local Institution - 213	Hawthorne	New York	United States	10532
10	New York Medical College	Hawthorne	New York	United States	10532
11	Mt. Sinai Medical Center Division of Hematology/Oncology	New York	New York	United States	10029
12	Cleveland Clinic	Cleveland	Ohio	United States	44195
13	Ohio State University Arthur G. James Cancer Hospital	Columbus	Ohio	United States	43210-1240
14	Local Institution - 210	Pittsburgh	Pennsylvania	United States	15232
15	University of Pittsburgh Medical Center - Cancer Pavilion	Pittsburgh	Pennsylvania	United States	15232
16	Local Institution - 212	San Antonio	Texas	United States	78229
17	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
18	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109-1023
19	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
20	Tom Baker Cancer Center	Calgary	Alberta	Canada	T2N 4N2
21	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
22	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 2M9
23	Alexandra Hospital, University of Athens	Athens		Greece	11528
24	Azienda Ospedaliera Citta della Salute e della Scienza di Torino	Torino		Italy	01012
25	Local Institution - 320	Torino		Italy	01012