A Study to Determine Dose and Tolerability of CC-220 Monotherapy, in Combination With Dexamethasone, and in Combination With Dexamethasone and Daratumumab or Bortezomib in Subjects With Relapsed and Refractory Multiple Myeloma (MM)

Status: Active

Description

This is a multicenter, multi-country, open-label, Phase 1b / 2a dose-escalation study consisting of two parts: dose escalation (Part 1) for CC-220 MonoT, CC-220 in combination with DEX, CC-220 in combination with DEX and DARA, CC-220 in combination with DEX and BTZ and CC-220 in combination with DEX and CFZ; and the expansion of the RP2D (Part 2) for CC-220 MonoT and CC-220 in combination with DEX (DoubleT).

Eligibility Criteria

Inclusion Criteria

  • Subjects must have a documented diagnosis of Multiple Myeloma and have measurable disease defined as:
  • M-protein (serum and/or urine protein electrophoresis (sPEP or uPEP)): sPEP ≥0.5 g/dL or uPEP ≥200 mg/24 hours and/or
  • Light chain Multiple Myeloma without measurable disease in the serum or urine: serum immunoglobulin free light chain ≥ 10 mg/dL (100 mg/L) and abnormal serum immunoglobulin kappa lambda free light chain ratio
  • All subjects must have documented disease progression on or within 60 days from the last dose of their last myeloma therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2

Exclusion Criteria

  • Subject has nonsecretory or oligosecretory multiple myeloma
  • Subjects with Plasma Cell leukemia or amyloidosis
  • Any of the following laboratory abnormalities
  • Absolute neutrophil count (ANC) <1,000/μL
  • Platelet count <75,000/μL
  • Corrected serum calcium >13.5 mg/dL (>3.4 mmol/L)
  • Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT)≥2.0 x upper limit of normal (ULN)
  • Serum total bilirubin and alkaline phosphatase >1.5 x ULN
  • Subjects with serious renal impairment ([CrCl] <50 mL/min) or requiring dialysis would be excluded
  • Subjects with peripheral neuropathy ≥Grade 2

Locations & Contacts

Arizona

Scottsdale
Mayo Clinic in Arizona
Status: Active
Name Not Available

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: Active
Contact: Sagar Lonial
Phone: 404-778-1868
Email: sloni01@emory.edu

Maryland

Baltimore
University of Maryland / Greenebaum Cancer Center
Status: Active
Contact: Emily Lederer
Phone: 410-328-7558
Email: elederer@umm.edu

Massachusetts

Boston
Brigham and Women's Hospital
Status: Active
Name Not Available
Dana-Farber Cancer Institute
Status: Active
Name Not Available
Massachusetts General Hospital Cancer Center
Status: Active
Name Not Available

Michigan

Ann Arbor
University of Michigan Comprehensive Cancer Center
Status: Approved
Name Not Available
Detroit
Wayne State University / Karmanos Cancer Institute
Status: Active
Name Not Available

New Jersey

Hackensack
Hackensack University Medical Center
Status: Active
Name Not Available

New York

New York
Icahn School of Medicine at Mount Sinai
Status: Active
Name Not Available

Ohio

Cleveland
Case Comprehensive Cancer Center
Status: In review
Name Not Available
Columbus
Ohio State University Comprehensive Cancer Center
Status: In review
Name Not Available

Pennsylvania

Philadelphia
University of Pennsylvania / Abramson Cancer Center
Status: Active
Name Not Available

Trial Objectives and Outline

Subjects assigned to CC-220 monotherapy, who develop progressive disease (PD) will have the option to receive DEX in addition to CC-220 after consultation with the Medical Monitor. The dose of CC-220 will not be higher than the dose of CC-220 used in combination with dexamethasone in Cohort B that has been determined to be safe. Progressive disease must be confirmed in accordance with international myeloma working group (IMWG) criteria. The starting dose of DEX will be 40 mg for subjects who are ≤75 years of age and 20 mg for subjects who are >75 years of age, given once weekly. This treatment will continue until PD, unacceptable toxicity or the subject withdraws consent. For Cohorts A and B, the starting dose level of CC-220, dose level 1, is 0.3 mg. A dose level -1, of 0.15 mg, may also be evaluated if the starting dose level of 0.3 mg for 21 days of a 28-day cycle is not tolerated. For Cohorts E and F, the starting dose level of CC-220, dose level 1, is one dose level below the maximum dose for Cohort B that has been determined to be safe by the dose escalation committee (DEC) at the start of enrollment for both cohorts. For Cohort E in addition to CC-220 and DEX, daratumumab will be administered intravenously (IV) at a 16mg/kg dose. For Cohort F in addition to CC-220 and DEX, bortezomib will be administered subcutaneous (SC) at a 1.3mg/m2 dose. All subjects with a minimal response (MR) or better who discontinue study treatment in Part 1 or Part 2 of the study for a reason other than PD or withdrawal of consent from the study will be followed for response assessment every 28 days (every 21 days for Cohort F) until PD. The study will be conducted in compliance with the International Council for Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good Clinical Practice (GCP) and applicable regulatory requirements. The initiation of Part 2 will begin when the RP2D is established in Part 1 in either Cohort A or Cohort B. Either cohort may begin once the RP2D is determined for each cohort independently during Part 1. All expansion decisions will be determined by the DEC after review of all safety, PK, biomarker and preliminary efficacy data, as applicable. During Part 2, the Independent Expert Reviewer will review safety data and any other data deemed relevant so that subject safety is ensured.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Celgene

Trial IDs

Primary ID CC-220-MM-001
Secondary IDs NCI-2016-01463, U1111-1182-9200, 2016-000860-40
Clinicaltrials.gov ID NCT02773030