A Study to Determine Dose, Safety, Tolerability, Drug Levels, and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Participants With Multiple Myeloma
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| ClinicalTrials.gov Identifier: NCT02773030 |
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Recruitment Status :
Active, not recruiting
First Posted : May 16, 2016
Last Update Posted : April 22, 2024
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Multiple Myeloma | Drug: CC-220 Drug: Dexamethasone Drug: Daratumumab Drug: Bortezomib Drug: Carfilzomib | Phase 1 Phase 2 |
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.
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 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 recommended phase 2 dose (RP2D) is established in Part 1 in either Cohort A, Cohort B, Cohort E or Cohort F. The cohorts 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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 532 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 as Monotherapy and in Combination With Other Treatments in Subjects With Multiple Myeloma |
| Actual Study Start Date : | October 14, 2016 |
| Estimated Primary Completion Date : | April 30, 2024 |
| Estimated Study Completion Date : | February 6, 2028 |
| Arm | Intervention/treatment |
|---|---|
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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
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Drug: CC-220
Specified dose on specified days
Other Name: Iberdomide |
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Experimental: Cohort B: CC-220 in combination with Dexamethasone (DEX) - 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. |
Drug: CC-220
Specified dose on specified days
Other Name: Iberdomide Drug: Dexamethasone Specified dose on specified days
Other Name: Decadron |
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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 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 |
Drug: CC-220
Specified dose on specified days
Other Name: Iberdomide Drug: Dexamethasone Specified dose on specified days
Other Name: Decadron |
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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 a dose of 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. |
Drug: CC-220
Specified dose on specified days
Other Name: Iberdomide Drug: Dexamethasone Specified dose on specified days
Other Name: Decadron Drug: Daratumumab Specified dose on specified days
Other Name: Darzalex |
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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, and 8 at cycle ≥9 of each 21-day cycle. |
Drug: CC-220
Specified dose on specified days
Other Name: Iberdomide Drug: Dexamethasone Specified dose on specified days
Other Name: Decadron Drug: Bortezomib Specified dose on specified days
Other Name: Velcade |
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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, and 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 |
Drug: CC-220
Specified dose on specified days
Other Name: Iberdomide Drug: Dexamethasone Specified dose on specified days
Other Name: Decadron Drug: Carfilzomib Specified dose on specified days
Other Name: Kyprolis |
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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 C1D2; 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, and 23 of each 28-day cycle. The DEX dose will be 20 mg. |
Drug: CC-220
Specified dose on specified days
Other Name: Iberdomide Drug: Dexamethasone Specified dose on specified days
Other Name: Decadron Drug: Carfilzomib Specified dose on specified days
Other Name: Kyprolis |
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Experimental: Cohort I: CC-220 in combination with DEX in post BCMA RRMM - 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, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle. |
Drug: CC-220
Specified dose on specified days
Other Name: Iberdomide Drug: Dexamethasone Specified dose on specified days
Other Name: Decadron |
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Experimental: Cohort J1: CC-220 in combination with DEX and BTZ in NDMM - Part 2
Oral CC-220 at 1.0mg, 1.3mg or 1.6mg administered at cycles 1 to 8 on Days 1 to 14 of each 21-day cycle and cycles ≥ 9 on Days 1 to 21 of each 28-day cycle. 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. |
Drug: CC-220
Specified dose on specified days
Other Name: Iberdomide Drug: Dexamethasone Specified dose on specified days
Other Name: Decadron Drug: Bortezomib Specified dose on specified days
Other Name: Velcade |
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Experimental: Cohort J2: 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. |
Drug: CC-220
Specified dose on specified days
Other Name: Iberdomide Drug: Dexamethasone Specified dose on specified days
Other Name: Decadron Drug: Bortezomib Specified dose on specified days
Other Name: Velcade |
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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. |
Drug: CC-220
Specified dose on specified days
Other Name: Iberdomide Drug: Dexamethasone Specified dose on specified days
Other Name: Decadron Drug: Daratumumab Specified dose on specified days
Other Name: Darzalex |
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Experimental: Cohort C: CC-220 Monotherapy in RRMM - Part 2
CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.
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Drug: CC-220
Specified dose on specified days
Other Name: Iberdomide |
- Establish maximum tolerated doses (MTDs) of CC-220 as monotherapy and in combination with other treatment [ Time Frame: Approximately 3 years ]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)
- Establish Recommended Phase 2 doses (RP2Ds) of CC-220 as monotherapy and in combination with other treatment [ Time Frame: Approximately 3 years ]RP2D is defined as the dose selected for phase 2 based on safety, pharmacokinetics and biomarker data from phase 1 of the study
- Overall response rate (ORR) of CC-220 in combination with Dexamethasone (DEX) in Cohort D [ Time Frame: Approximately 5 years ]Tumor response, including progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria (Kumar, 2011) in CC-220 in combination with DEX
- Adverse Events (AEs) [ Time Frame: Approximately 5 years ]Type, frequency, seriousness and severity of adverse events (AEs) (and AEs of special interest) and relationship of AEs to investigational product
- Overall response rate (ORR) [ Time Frame: Approximately 5 years ]Tumor response, including progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria (Kumar, 2016) for subjects who achieved partial response (PR) or better
- Time to Response (TTR) [ Time Frame: Approximately 5 years ]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)
- Duration of Response (DOR) [ Time Frame: Approximately 5 years ]Is defined as Time from the first documentation of response (PR or greater) to the first documentation of Progressive disease (PD)
- Progression-free Survival (PFS) [ Time Frame: Approximately 5 years ]Time from the first dose of investigational product (IP) to the first documentation of PD or death from any cause, whichever occurs first
- Overall Survival (OS) in Part 2 relapsed and refractory multiple myeloma (RRMM) cohorts [ Time Frame: Approximately 5 years ]Time from first dose of IP to death due to any cause
- Pharmacokinetics - Area under the plasma concentration-time curve from time zero to tau, where tau is the dosing interval (AUC[TAU]) [ Time Frame: Approximately 1 year ]
- Pharmacokinetics - Maximum plasma concentration of drug (Cmax) [ Time Frame: Approximately 1 year ]
- Pharmacokinetics - Time to maximum plasma concentration of drug (Tmax) [ Time Frame: Approximately 1 year ]
- Very good partial response or better rate (VGPR) [ Time Frame: Approximately 4 years ]Tumor response, including progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria (Kumar, 2016) for subjects who achieved VGPR or better
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2
- Relapsed and refractory multiple myeloma (RRMM) participants must have documented disease progression on or within 60 days from the last dose of their last myeloma therapy
- Newly diagnosed multiple myeloma (NDMM) participants must have documented diagnosis with previously untreated symptomatic multiple myeloma (MM)
- Participants in Cohorts J1 and K are those for whom autologous stem cell transplantation is not planned for initial therapy or are not considered by the investigator as eligible for high-dose chemotherapy and autologous stem cell transplantation
Exclusion Criteria:
- Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the participant from participating in the study
- Nonsecretory multiple myeloma
- Prior history of malignancies, other than MM and select non-invasive malignancies, unless the participant has been free of the disease for ≥ 5 years
Other protocol-defined inclusion/exclusion criteria apply
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02773030
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| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Celgene |
| ClinicalTrials.gov Identifier: | NCT02773030 |
| Other Study ID Numbers: |
CC-220-MM-001 U1111-1182-9200 ( Registry Identifier: WHO ) 2016-000860-40 ( EudraCT Number ) |
| First Posted: | May 16, 2016 Key Record Dates |
| Last Update Posted: | April 22, 2024 |
| Last Verified: | April 2024 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Multiple Myeloma Relapsed Refractory Pharmacokinetics Safety Efficacy CC-220 |
Relapsed and refractory multiple myeloma Dexamethasone Daratumumab Bortezomib Newly diagnosed multiple myeloma Newly diagnosed multiple myeloma transplant non-eligible |
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Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases |
Dexamethasone Bortezomib Daratumumab Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents |