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

Conditions

• Multiple Myeloma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• CC-220 — DRUG
  CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.
• Dexamethasone — DRUG
  Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects \>75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.
• Daratumumab — DRUG
  Specified dose on specified days
• Bortezomib — DRUG
  Specified dose on specified days
• Carfilzomib — DRUG
  Intravenous (IV) CFZ administered at a starting dose of 20 mg/m2 on C1D1 and C1D2; and at a dose level specified by cohort dose level thereafter Days 1, 2, 8, 9, 15, 16 of each 28-day cycle.
• Daratumumab - 16mg/kg — DRUG
  Daratumumab (DARA) 16mg/kg by intravenous infusion 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.
• Bortezomib (BTZ) — DRUG
  Bortezomib 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.
• Daratumumab- 1800mg — DRUG
  Daratumumab (DARA) 1800 mg by subcutaneous injection 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.

Study Details

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

Key Dates

Start date

Oct 14, 2016

Status verified

Mar 2026

Primary completion

May 9, 2024

Completion

Jul 28, 2028

Study Design

Enrollment

466 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Cohort A: CC-220 Monotherapy - Part 1
  Oral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle
• Experimental: Cohort B: CC-220 in combination with Dexamethasone - Part 1
  * Oral 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.
• Experimental: Cohort D: CC-220 in combination with Dexamethasone - Part 2
  * Oral 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.
• Experimental: Cohort E: CC-220 with DEX and daratumumab (DARA) - Part 1
  * Oral 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 16mg/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. Once the MTD and/or RP2D is determined in Cohort E (CC-220Dd), subjects will be enrolled at this dose level using SC DARA. * Oral 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. * Subcutaneous DARA at dose 1800 mg over 3 to 5 minutes 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.
• Experimental: Cohort F: CC-220 with DEX and bortezomib - Part 1
  * Oral 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.
• Experimental: Cohort G1-CC-220 in combination with CFZ and DEX -Part 1
  * Oral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle * Intravenous (IV) CFZ (Carfilzomib)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 (Dexamethasone) 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
• Experimental: Cohort G2 - CC-220 in combination with CFZ and DEX - Part 1
  * Oral 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
• Experimental: CohortI-CC-220 in combination with DEX in post BCMA RRMM-Part2
  * Oral 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, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.
• Experimental: CohortJ1:CC-220 in combination with DEX and BTZ in NDMM-Part 2
  * Oral CC-220 at Recommended Phase 2 Dose from Day 1-14 of each 21-day cycle (Cycle 1 to 8) and from Day 1-21 of each 28-day cycle (Cycle 9 and above). * Oral DEX at Cycles 1 to 8, 20 mg (≤ 75 years old) or 10 mg (\> 75 years old) on Days 1, 2, 4, 5, 8, 9, 11 and 12 of each 21-day cycle and Cycles ≥ 9, 40 mg (≤ 75 years old) or 20 mg (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle. * Subcutaneous BTZ at dose 1.3 mg/m2 on Days 1, 4, 8 and 11 at Cycle 1-8 of each 21-day cycle.
• Experimental: CohortJ2:CC-220 in combination with DEX and BTZ in NDMM-Part 2
  * Oral CC-220 at Recommended Phase 2 Dose from Day 1-14 of each 21-day cycle. * Oral DEX at 20 mg/day (≤ 75 years old) or 10 mg/day (\> 75 years old) for Cycles 1 to 6 on Days 1, 2, 4, 5, 8, 9, 11 and 12 of a 21-day cycle. * Subcutaneous BTZ at dose 1.3 mg/m2 on Days 1, 4, 8 and 11 at Cycle 1-6 of each 21-day cycle.
• Experimental: Cohort K: CC-220 with DEX and DARA in NDMM and not autologous stem cell transplant eligible - Part 2
  Oral CC-220 at 1.0mg, 1.3mg or 1.6mg from Days 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, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle. Subcutaneous DARA at 1800 mg over 3 to 5minutes on Days 1, 8, 15, and 22 at cycle 1-2 of a 28-day cycle, Days1, and 15 at cycle 3-6 of a 28-day cycle, and Day1 at cycle ≥7 of each 28-day cycle.

Primary Outcome Measure

Number of Participants With Dose Limiting Toxicities in Part 1. [ Time Frame: From first dose to 28 days post last dose (up to 28 days) ]

Locations (58)

Find similar trials in Scottsdale, AZ

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