Clinical Trials /

A Study to Determine Dose, Safety, Tolerability and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Subjects With Multiple Myeloma

NCT02773030

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, CC-220 in combination with DEX (DoubleT) for Relapsed Refractory Multiple Myeloma and CC-220 in combination with DEX and BTZ for Newly Diagnosed Multiple Myeloma.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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)
  • Official Title: A Phase 1b/2a Multicenter, Open-label, Dose-escalation Study to Determine the Maximum Tolerated Dose, Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of CC-220 Monotherapy and in Combination With Other Treatments in Subjects With Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: CC-220-MM-001
  • SECONDARY ID: U1111-1182-9200
  • SECONDARY ID: 2016-000860-40
  • NCT ID: NCT02773030

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
CC-220IberdomideCohort A: CC-220 Monotherapy - Part 1
DexamethasoneDecadronCohort B: CC-220 in combination with Dexamethasone - Part 1
DaratumumabDarzalexCohort E: CC-220 with DEX and daratumumab (DARA) - Part 1
Bortezomib (BTZ)VelcadeCohort F: CC-220 with DEX and bortezomib - Part 1
CarfilzomibKyprolisCohort G1 - CC-220 in combination with once weekly CFZ and DEX

Purpose

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).

Detailed Description

      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 Arms

NameTypeDescriptionInterventions
Cohort A: CC-220 Monotherapy - Part 1ExperimentalOral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle
  • CC-220
Cohort B: CC-220 in combination with Dexamethasone - Part 1ExperimentalOral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle. For subjects ≤ 75 years old, oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, DEX will be administered at 20 mg on Days 1, 8,15, and 22 of each 28-day cycle. Subjects who surpass the age of 75 years while on treatment may be switched to the 20 mg QD dosage based on the investigator's best judgment.
  • CC-220
  • Dexamethasone
Cohort C: CC-220 Monotherapy - Part 2ExperimentalOral CC-220 at Recommended Phase 2 dose (RP2D) from Day 1-21 of each 28-day cycle
  • CC-220
Cohort D: CC-220 in combination with Dexamethasone - Part 2ExperimentalOral CC-220 at Recommended Phase 2 dose (RP2D) from Day 1-21 of each 28-day cycle Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.
  • CC-220
  • Dexamethasone
Cohort E: CC-220 with DEX and daratumumab (DARA) - Part 1ExperimentalOral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle. Oral DEX for subjects ≤ 75 years old at 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, oral DEX at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle. Intravenous DARA at dose 16 mg/kg on Days 1, 8, 15, and 22 at cycle 1-2, Days 1, 15 at cycle 3-6, and Day 1 at cycle ≥7 of each 28-day cycle.
  • CC-220
  • Dexamethasone
  • Daratumumab
Cohort F: CC-220 with DEX and bortezomib - Part 1ExperimentalOral CC-220 at dose specified by cohort dose level from Day 1-14 of each 21-day cycle. Oral DEX for subjects ≤ 75 years old at 40 mg on Days 1, 8, and 15 of each 21-day cycle. For subjects >75 years old, oral DEX at 20 mg on Days 1, 8, and 15 of each 21-day cycle. Subcutaneous BTZ at dose 1.3 mg/m^2 on Days 1, 4, 8 and 11 at cycle 1-8, and Days 1, 8 at cycle ≥9 of each 21-day cycle.
  • CC-220
  • Dexamethasone
  • Bortezomib (BTZ)
Cohort G1 - CC-220 in combination with once weekly CFZ and DEXExperimentalOral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle Intravenous (IV) CFZ administered at a starting dose of 20 mg/m2 on C1D1; and at a dose specified by cohort dose level thereafter on days 1, 8, 15 of each 28-day cycle Oral DEX on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects ≤ 75 years old, the DEX dose will be 40 mg. For subjects > 75 years old, the DEX dose will be 20 mg
  • CC-220
  • Dexamethasone
  • Carfilzomib
Cohort G2 -CC-220 in combination with twice weekly CFZ and DEXExperimentalOral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle Intravenous (IV) CFZ administered at a starting dose of 20 mg/m2 on C1D1; and at a dose level specified by cohort dose level thereafter Days 1, 2, 8, 9, 15, 16 of each 28-day cycle Oral DEX on Days 1, 2, 8, 9, 15, 16, 22, 23 of each 28-day cycle. The DEX dose will be 20 mg
  • CC-220
  • Dexamethasone
  • Carfilzomib

Eligibility Criteria

        Inclusion Criteria:

          1. 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

          2. All subjects must have documented disease progression on or within 60 days from the
             last dose of their last myeloma therapy

          3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2

        Exclusion Criteria:

          1. Subject has nonsecretory or oligosecretory multiple myeloma

          2. Subjects with Plasma Cell leukemia or amyloidosis

          3. 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

          4. Subjects with peripheral neuropathy ≥Grade 2
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated doses (MTDs) of CC-220 as monotherapy and in combination with other treatment
Time Frame:Approximately 1 year
Safety Issue:
Description:Establish the maximum tolerated doses (MTDs) of CC-220 monotherapy, in combination with DEX, and in combination with DEX and daratumumab (CC-220Dd), in combination with DEX and bortezomib (CC-220Vd), and in combination with DEX and carfilzomib (CC-220Kd)

Secondary Outcome Measures

Measure:Adverse Events (AEs)
Time Frame:Approximately 3 years
Safety Issue:
Description:Type, frequency, seriousness and severity of adverse events (AEs) (and AEs of special interest) and relationship of AEs to investigational product
Measure:Overall response rate (ORR)
Time Frame:Approximately 3 years
Safety Issue:
Description:Tumor response, including progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria (Rajkumar, 2011)
Measure:Time to Response (TTR)
Time Frame:Approximately 3 years
Safety Issue:
Description:Is defined as the time from the first date of dosing of IP to the first date of documented response (partial response [PR] or greater).
Measure:Duration of Response (DOR)
Time Frame:Approximately 3 years
Safety Issue:
Description:Is defined as Time from the first documentation of response (PR or greater) to the first documentation of Progressive disease (PD)
Measure:Pharmacokinetics ‐AUC 0-τ
Time Frame:Approximately 1 year
Safety Issue:
Description:Area under the plasma concentration-time curve from time zero to tau, where tau is the dosing interval
Measure:Pharmacokinetics ‐Cmax
Time Frame:Approximately 1 year
Safety Issue:
Description:Maximum plasma concentration of drug
Measure:Pharmacokinetics ‐Tmax
Time Frame:Approximately 1 year
Safety Issue:
Description:Time to Maximum plasma concentration of drug
Measure:Pharmacokinetics ‐t1/2
Time Frame:Approximately 1 year
Safety Issue:
Description:Terminal-phase elimination half life
Measure:Pharmacokinetics ‐CLss/F
Time Frame:Approximately 1 year
Safety Issue:
Description:Apparent total plasma clearance when dosed daily
Measure:Pharmacokinetics ‐Vss/F
Time Frame:Approximately 1 year
Safety Issue:
Description:Apparent total volume of distribution at steady state when dosed orally
Measure:Progression-free Survival (PFS)
Time Frame:Approximately 3 years
Safety Issue:
Description:Time from the first dose of investigational product (IP) to the first documentation of PD or death from any cause, whichever occurs first
Measure:Overall Survival (OS) in Part 2
Time Frame:Approximately 3 years
Safety Issue:
Description:Time from first dose of IP to death due to any cause

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Celgene

Trial Keywords

  • Multiple Myeloma
  • Relapsed
  • Refractory
  • Pharmacokinetics
  • Safety
  • Efficacy
  • CC-220
  • Relapsed and refractory multiple myeloma
  • Dexamethasone
  • Daratumumab
  • Bortezomib

Last Updated

October 20, 2019