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

Phase 1
Completed
Conditions
Multiple Myeloma
Interventions
Registration Number
NCT02189343
Lead Sponsor
Celgene
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.

Detailed Description

To determine the maximum tolerated dose (MTD), if present, and to identify a recommended dose and schedule of ricolinostat administered in an alternative liquid formulation (ALF) (10mg/mL) in combination with pomalidomide and low-dose dexamethasone in patients with relapsed or relapsed-and-refractory multiple myeloma.

To evaluate the safety and any anti-tumor activity of ricolinostat administered in combination with pomalidomide and dexamethasone as treatment for patients with relapsed or relapsed-and-refractory multiple myeloma, including duration of response.

To assess the Pharmacokinetics and Pharmacodynamics of all three medications administered in combination, and to assess the Pharmacokinetics of ricolinostat and pomalidomide specifically. An evaluation of the relationship between response and biomarkers relating to interacellular acetylation may also be completed.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
16
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Dose Escalation CohortACY-1215 in combination with pomalidomide and dexamethasoneDose Escalating Cohorts of ACY-1215 in combination with pomalidomide and dexamethasone.
Primary Outcome Measures
NameTimeMethod
Determine Maximum Tolerated Dose (MTD) if any, and recommended dose scheduleEvery 56 days on treatment, estimated average of 4 months.

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).

Secondary Outcome Measures
NameTimeMethod
Anti-Tumor ActivityUpon completion of a 28-day treatment cycle and for the duration of treatment, an estimated average of 4 months.

Anti-tumor activity will be measured by objective response to treatment as assessed by the site Investigators using International Myeloma Working Group (IMWG) Uniform Response criteria. Anti-tumor activity will also be measured by duration of response, time to response, and time to progression. The Response rate will be the percentage of patients who achieve PR or better. The number of patients who have at least MR or better will also be collected as clinical benefit response. Progression-free survival (PFS) will be defined as the time from first dose of study treatment to the first documentation of disease progression or death from any cause during the study. For responders, time to tumor response and response duration will be analyzed.

PharmacokineticsUp to 8 days post first dose

Plasma levels of ACY-1215 will be measured to assess the single and multiple dose PK of AC-1215 in combination with pomalidomide and low-dose dexamethasone. Plasma levels of pomalidomide will be measured to assess the PK of pomalidomide in combination with ACY-1215 and low-dose dexamethasone.

PharmacodynamicsUp to 24 hours post first dose

Exposure response of ACY-1215 in combination with pomalidomide and low-dose dexamethasone, including biomarkers relating to intracellular protein acetylation, protein levels, mRNA and microRA expression profiles.

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

To assess the type, frequency, and severity of adverse events (AEs) and relationship of AEs to study drug.

Trial Locations

Locations (3)

UT Southwestern Medical Center Simmons Comprehensive Cancer Center

🇺🇸

Dallas, Texas, United States

CTRC at The UT Health Science Center at San Antonio

🇺🇸

San Antonio, Texas, United States

University of Utah Huntsman Cancer Institute

🇺🇸

Salt Lake City, Utah, United States

UT Southwestern Medical Center Simmons Comprehensive Cancer Center
🇺🇸Dallas, Texas, United States
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