Phase 1b Study Evaluating ACY-1215 (Ricolinostat) in Combination With Pomalidomide and Dexamethasone in Relapsed or Relapsed-and-Refractory Multiple Myeloma

NCT02189343 | Completed Phase 1 DMC

• 1 other identifier: ACE-MM-104
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 3

Brief Summary

To determine the maximum tolerated dose (MTD), if present, and dose schedule of ACY-1215 (ricolinostat) in combination with pomalidomide and low-dose dexamethasone in patients with relapsed-and-refractory multiple myeloma.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Relapsed and Refractory; Refractory Disease; Progressive Disease; Pomalidomide; Dexamethasone; Proteasome Inhibitor; Ricolinostat

Outcome Measures

Primary Outcomes (1)

• Determine Maximum Tolerated Dose (MTD) if any, and recommended dose schedule

  Identify the MTD of ACY-1215 administered in an alternative liquid formulation (ALF) if present, and identify a recommended dose and schedule. Patients will be followed for completion of 6 28-day Cycles of Study Treatment (for ITT Population analysis).

  Every 56 days on treatment, estimated average of 4 months.

Secondary Outcomes (4)

• Safety

  Upon completion of a 28-day treatment cycle and for the duration of treatment, an estimated average of 4 months.

• Anti-Tumor Activity

  Upon completion of a 28-day treatment cycle and for the duration of treatment, an estimated average of 4 months.

• Pharmacokinetics

  Up to 8 days post first dose

• Pharmacodynamics

  Up to 24 hours post first dose

Study Arms (1)

Dose Escalation Cohort

EXPERIMENTAL

Dose Escalating Cohorts of ACY-1215 in combination with pomalidomide and dexamethasone.

Drug: ACY-1215 in combination with pomalidomide and dexamethasone

Interventions

ACY-1215 in combination with pomalidomide and dexamethasone DRUG

Escalating dose Cohorts to determine a potential Maximum Tolerated Dose to recommend for a dosing schedule.

Also known as: ACY-1215 (Ricolinostat), Pomalidomide, Dexamethasone

Dose Escalation Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients meeting all of the following criteria may be enrolled in the study:
• Must be able to understand and voluntarily sign an ICF.
• Must be registered into the mandatory POMALYST Risk Evaluation and Mitigation Strategy (REMS)™ program, and be willing and able to comply with the requirements of the POMALYST REMS™ program (Appendix 9.3).
• Must be ≥ 18 years of age at the time of signing the ICF.
• Must be able to adhere to the study visit schedule and other protocol requirements.
• Must have a documented diagnosis of MM and have relapsed or 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 for at least 1 cycle of treatment to at least 1 prior regimen and then developed PD. Relapsed and relapsed-and-refractory patients must have documented evidence of PD during or within 60 days (measured from the end of the last cycle) of completing treatment with the last antimyeloma drug regimen used just prior to study entry.
• Patients must have undergone prior treatment with at least 2 cycles of lenalidomide and at least 2 cycles of a proteasome inhibitor (either in a separate regimen or within the same regimen.
• Must not be a candidate for autologous stem cell transplant (ASCT), have declined the option of ASCT, or have relapsed after prior ASCT.
• Must have measurable levels of myeloma paraprotein in serum (≥ 0.5 g/dL) or urine (≥ 0.2 g/24 hours). Patients who do not have myeloma paraprotein must have serum free light chain (SFLC) concentration of ≥ 10 mg/dL, provided SFLC ratio is abnormal. Nonsecretory myeloma is excluded.
• Must have Eastern Cooperative Oncology Group performance status score of 0, 1, or 2.
• Females of childbearing potential must have a negative serum or urine pregnancy test as described in Appendix 9.3 for the POMALYST REMS™ program. Females of childbearing potential and males must either commit to continued abstinence from heterosexual intercourse or must abide by birth control requirements as described in Appendix 9.3 for the POMALYST REMS™ program.
• Must agree to refrain from donating blood while on study drug and for 28 days after discontinuation from this study.
• Must agree not to share study medication with another person.
• Must be able to take 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 of 2 to 3.

You may not qualify if:

• Patients meeting any of the following criteria will be excluded from enrollment in the study:
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the ICF or from following the study requirements.
• Pregnant or lactating females.
• Prior therapy with histone deacetylase inhibitor or pomalidomide.
• 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, or a platelet count \< 50,000 for patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells
• Hemoglobin \< 8 g/dL (\< 4.9 mmol/L; prior red blood cell transfusion or recombinant human erythropoietin use is permitted).
• 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.
• Serum glutamic oxaloacetic transaminase/aspartate aminotransferase, or serum glutamic pyruvic transaminase/alanine aminotransferase \> 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
• Ductal carcinoma in situ; or cervical intraepithelial neoplasia
• Carcinoma of the prostate with a current prostate-specific antigen below the upper limit of normal

Sponsors & Collaborators

• Celgene: lead

Study Sites (3)

UT Southwestern Medical Center Simmons Comprehensive Cancer Center

Dallas, Texas, 75390-8852, United States

Location

CTRC at The UT Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

University of Utah Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Recurrence; Disease; Disease Progression

Interventions

ricolinostat; pomalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Sumit Madan, MD

  The University of Texas Health Science Center at San Antonio

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2014
• First Posted: July 14, 2014
• Study Start: September 15, 2014
• Primary Completion: April 18, 2018
• Study Completion: April 30, 2018
• Last Updated: November 21, 2019

Record last verified: 2019-11

Locations

US (3)