NCT02773030 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-03-20

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Participants With Dose Limiting Toxicities in Part 1.

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outcome · POSTED

Overall Response Rate (ORR) in Cohort D and Cohort H2

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outcome · POSTED

Number of Participants With Treatment Related Adverse Events

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outcome · POSTED

Number of Participants With Treatment Emergent Adverse Events of Special Interest (AESI)

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outcome · POSTED

Very Good Partial Response Rate (ORR) in Cohort J1 and Cohort K

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outcome · POSTED

Overall Response Rate (ORR)

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outcome · POSTED

Time to Response (TTR)

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outcome · POSTED

Duration of Response

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outcome · POSTED

Progression Free Survival

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outcome · POSTED

Overall Survival for Cohort D, Cohort H2 and Cohort I

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outcome · POSTED

Auc(Tau)

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outcome · POSTED

Cmax

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outcome · POSTED

Tmax

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: 1\. All subjects in RRMM cohorts must have a documented diagnosis of Multiple Myeloma and have measurable disease defined as: 1. M-protein (serum and/or urine protein electrophoresis (sPEP or uPEP)): sPEP ≥0.5 g/dL or uPEP ≥200 mg/24 hours and/or 2. 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 in RRMM cohorts must have documented disease progression on or within 60 days from the last dose of their last myeloma therapy. Subjects who had CAR T therapy as their last myeloma therapy must have documented disease progression. 3\. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2 3. Subject must have documented diagnosis with previously untreated symptomatic MM as defined by the criteria below (Rajkumar, 2016): MM diagnostic criteria; \- Clonal bone marrow plasma cells ≥ 10% or biopsy-proven bony or extramedullary plasmacytoma \- Any one or more of the following myeloma defining events: * One or more of the following myeloma-related organ dysfunction (at least one of the following); • \[C\] Calcium elevation (serum calcium \> 0.25 mmol/L \[\> 1 mg/dL\] higher than the upper limit of laboratory normal or \> 2.75 mmol/L \[\> 11 mg/dL\]) • \[R\] Renal insufficiency (serum creatinine \> 2 mg/dl \[\> 177 μmol/L\] or creatinine clearance \< 40 ml/min) * \[A\] Anemia (hemoglobin \< 10 g/dl or \> 2 g/dL below the lower limit of laboratory normal) * \[B\] Bone lesions (lytic or osteopenic) one or more bone lesions on skeletal radiography, computed tomography (CT), or positron emission tomography (PET)/CT * One or more of the following biomarkers of malignancy: * Clonal bone marrow plasma cell percentage\* ≥ 60% * Abnormal serum free light-chain (FLC) ratio ≥ 100 (involved kappa) or \<0.01 (involved lambda) and involved FLC level must be ≥ 100 mg/L * \>1 focal lesion detected by magnetic resonance imaging (MRI) (at least 5 mm in size) AND have measurable disease, as assessed by central laboratory, defined by any of the following: \- Immunoglobulin (Ig)G myeloma: serum M-protein level ≥ 1.0 g/dL or urine M-protein level ≥ 200 mg/24 hours; or \- IgA, IgM, IgD, or IgE multiple myeloma: serum M-protein level ≥ 0.5 g/dL or urine M-protein level ≥ 200 mg/24 hours; or \- Light chain multiple myeloma without measurable disease in serum or urine: serum FLC ≥ 100 mg/L and abnormal kappa lambda (κ/λ) ratio 4. Subjects in Cohort J1 are not considered by the investigator as eligible for high-dose chemotherapy and autologous stem cell transplantation due to: \- Age ≥65 years, OR \- In subjects \<65 years: presence of important comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with autologous stem cell transplantation. 5\. Subjects in Cohort J2 are considered by the investigator as eligible for high-dose chemotherapy and autologous stem cell transplantation according to the institution's criteria based on age, medical history, cardiac and pulmonary status, overall health and condition, co-morbid condition(s), physical examination, and laboratory data. Exclusion Criteria: 1\. Subject has nonsecretory 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 for Part 1. For Part 2; platelet count \< 75,000/μL for subjects in whom \< 50% of bone marrow nucleated cells are plasma cells; otherwise platelet count \< 50,000/μL (transfusions are not permitted to achieve minimum platelet counts • 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 creatinine clearance (\[CrCl\] \<45 mL/min) or requiring dialysis would be excluded 4. Subjects with peripheral neuropathy ≥Grade 2
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Oral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle
intervention Names
Drug: CC-220
label
Cohort A: CC-220 Monotherapy - Part 1
type
EXPERIMENTAL
description
* 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.
intervention Names
Drug: CC-220
Drug: Dexamethasone
label
Cohort B: CC-220 in combination with Dexamethasone - Part 1
type
EXPERIMENTAL
description
* 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.
intervention Names
Drug: CC-220
Drug: Dexamethasone
label
Cohort D: CC-220 in combination with Dexamethasone - Part 2
type
EXPERIMENTAL
description
* 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.
intervention Names
Drug: CC-220
Drug: Dexamethasone
Drug: Daratumumab
Drug: Daratumumab - 16mg/kg
Drug: Daratumumab- 1800mg
label
Cohort E: CC-220 with DEX and daratumumab (DARA) - Part 1
type
EXPERIMENTAL
description
* 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.
intervention Names
Drug: CC-220
Drug: Dexamethasone
Drug: Bortezomib
Drug: Bortezomib (BTZ)
label
Cohort F: CC-220 with DEX and bortezomib - Part 1
type
EXPERIMENTAL
description
* 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
intervention Names
Drug: CC-220
Drug: Dexamethasone
Drug: Carfilzomib
label
Cohort G1-CC-220 in combination with CFZ and DEX -Part 1
type
EXPERIMENTAL
description
* 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
intervention Names
Drug: CC-220
Drug: Dexamethasone
Drug: Carfilzomib
label
Cohort G2 - CC-220 in combination with CFZ and DEX - Part 1
type
EXPERIMENTAL
description
* 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.
intervention Names
Drug: CC-220
Drug: Dexamethasone
label
CohortI-CC-220 in combination with DEX in post BCMA RRMM-Part2
type
EXPERIMENTAL
description
* 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.
intervention Names
Drug: CC-220
Drug: Dexamethasone
Drug: Bortezomib
Drug: Bortezomib (BTZ)
label
CohortJ1:CC-220 in combination with DEX and BTZ in NDMM-Part 2
type
EXPERIMENTAL
description
* 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.
intervention Names
Drug: CC-220
Drug: Dexamethasone
Drug: Bortezomib
Drug: Bortezomib (BTZ)
label
CohortJ2:CC-220 in combination with DEX and BTZ in NDMM-Part 2
type
EXPERIMENTAL
description
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.
intervention Names
Drug: Daratumumab
label
Cohort K: CC-220 with DEX and DARA in NDMM and not autologous stem cell transplant eligible - Part 2
type
EXPERIMENTAL

interventions

arm Group Labels
Cohort A: CC-220 Monotherapy - Part 1
Cohort B: CC-220 in combination with Dexamethasone - Part 1
Cohort D: CC-220 in combination with Dexamethasone - Part 2
Cohort E: CC-220 with DEX and daratumumab (DARA) - Part 1
Cohort F: CC-220 with DEX and bortezomib - Part 1
Cohort G1-CC-220 in combination with CFZ and DEX -Part 1
Cohort G2 - CC-220 in combination with CFZ and DEX - Part 1
CohortI-CC-220 in combination with DEX in post BCMA RRMM-Part2
CohortJ1:CC-220 in combination with DEX and BTZ in NDMM-Part 2
CohortJ2:CC-220 in combination with DEX and BTZ in NDMM-Part 2
description
CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.
name
CC-220
other Names
Iberdomide
type
DRUG
arm Group Labels
Cohort B: CC-220 in combination with Dexamethasone - Part 1
Cohort D: CC-220 in combination with Dexamethasone - Part 2
Cohort E: CC-220 with DEX and daratumumab (DARA) - Part 1
Cohort F: CC-220 with DEX and bortezomib - Part 1
Cohort G1-CC-220 in combination with CFZ and DEX -Part 1
Cohort G2 - CC-220 in combination with CFZ and DEX - Part 1
CohortI-CC-220 in combination with DEX in post BCMA RRMM-Part2
CohortJ1:CC-220 in combination with DEX and BTZ in NDMM-Part 2
CohortJ2:CC-220 in combination with DEX and BTZ in NDMM-Part 2
description
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.
name
Dexamethasone
other Names
Decadron
type
DRUG
arm Group Labels
Cohort E: CC-220 with DEX and daratumumab (DARA) - Part 1
Cohort K: CC-220 with DEX and DARA in NDMM and not autologous stem cell transplant eligible - Part 2
description
Specified dose on specified days
name
Daratumumab
other Names
Darzalex
type
DRUG
arm Group Labels
Cohort F: CC-220 with DEX and bortezomib - Part 1
CohortJ1:CC-220 in combination with DEX and BTZ in NDMM-Part 2
CohortJ2:CC-220 in combination with DEX and BTZ in NDMM-Part 2
description
Specified dose on specified days
name
Bortezomib
other Names
Velcade
type
DRUG
arm Group Labels
Cohort G1-CC-220 in combination with CFZ and DEX -Part 1
Cohort G2 - CC-220 in combination with CFZ and DEX - Part 1
description
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.
name
Carfilzomib
other Names
Kyprolis
type
DRUG
arm Group Labels
Cohort E: CC-220 with DEX and daratumumab (DARA) - Part 1
description
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.
name
Daratumumab - 16mg/kg
other Names
Darzalex
type
DRUG
arm Group Labels
Cohort F: CC-220 with DEX and bortezomib - Part 1
CohortJ1:CC-220 in combination with DEX and BTZ in NDMM-Part 2
CohortJ2:CC-220 in combination with DEX and BTZ in NDMM-Part 2
description
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.
name
Bortezomib (BTZ)
other Names
Velcade
type
DRUG
arm Group Labels
Cohort E: CC-220 with DEX and daratumumab (DARA) - Part 1
description
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.
name
Daratumumab- 1800mg
other Names
Darzalex Faspro
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 466
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
The dose-limiting toxicity (DLT) population includes subjects who missed no more than 4 doses of CC-220, 2 doses of DEX, 1 dose of IV DARA (Cohort E), 1 dose of BTZ (Cohort F), or 1 dose of CFZ (Cohort G1 or G2) during Cycle 1 for reasons other than DLT. This population will be used for analyzing the primary endpoint regarding the determination of the MTD. Hematologic DLTs: Grade 4 neutropenia (ANC \<500/μL for \>5 days) Grade 3 neutropenia (ANC \<1,000/μL) with fever ≥38.5°C Grade 4 thrombocytopenia (platelet count \<25,000/μL) or Grade 3 thrombocytopenia with bleeding or need for platelet transfusion Any other grade 4 hematologic toxicity, except anemia, not resolving to pretreatment baseline within 72 hours. Non-hematologic DLT: Any non-hematological toxicity ≥ Grade 3, except alopecia and nausea controlled by medical management.
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)
description
Tumor response, including progressive disease (PD) according to the IMWG Uniform Response Criteria (Kumar, 2016) for subjects who achieved partial response (PR) or better.
measure
Overall Response Rate (ORR) in Cohort D and Cohort H2
time Frame
Approximately on average (Cohort D: 21.14 weeks, Cohort H2: 22.11 Weeks)

secondary Outcomes

description
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.
measure
Number of Participants With Treatment Related Adverse Events
time Frame
Approximately on average of (Cohort A: 16.23 Cohort B: 10.32 Cohort D: 18.68 Cohort E: 15.65 Cohort F: 12.66 Cohort G: 16.03 Cohort H1: 17.22 Cohort H2: 21.07 Cohort I: 17.10 Cohort J: 20.56 Cohort K: 13.56) Months
description
An adverse event of special interest (AESI) is one of scientific and medical interest specific to understanding the safety profile of the Investigational Product, CC-220, and may require close monitoring and rapid communication by the Investigator to the Sponsor. An AESI may be serious or nonserious. The rapid reporting of AESIs allows ongoing surveillance of these events in order to characterize and understand their association with the use of this investigational product.
measure
Number of Participants With Treatment Emergent Adverse Events of Special Interest (AESI)
time Frame
Approximately on average of (Cohort A: 16.23 Cohort B: 10.32 Cohort D: 18.68 Cohort E: 15.65 Cohort F: 12.66 Cohort G: 16.03 Cohort H1: 17.22 Cohort H2: 21.07 Cohort I: 17.10 Cohort J: 20.56 Cohort K: 13.56) Months
description
The very good partial response or better (≥ VGPR) rate is defined as the proportion of subjects with best response of VGPR or better during the trial without administration of myeloma therapy other than study treatment. The ≥ VGPR rate with 95% confidence interval (CI) together with the proportions in each response category based on the IMWG Uniform Response Criteria.
measure
Very Good Partial Response Rate (ORR) in Cohort J1 and Cohort K
time Frame
On Average of (Cohort J: 86.21, Cohort K: 56.29) Weeks
description
Tumor response, including progressive disease (PD) according to the IMWG Uniform Response Criteria (Kumar, 2016) for subjects who achieved partial response (PR) or better.
measure
Overall Response Rate (ORR)
time Frame
On Average of (Cohort A: 44.96, Cohort B: 32.79, Cohort D: 21.14, Cohort E: 53.74, Cohort F: 46.34, Cohort G: 63.26, Cohort H1: 58.10, Cohort H2: 22.11, Cohort I: 20.96, Cohort J: 86.21, Cohort K: 56.29) Weeks
description
Time to response is defined as the time from the first dose date of study treatment to the first date of documented response (PR or better). Time to response will be summarized for responders using descriptive statistics by cohort and dose level.
measure
Time to Response (TTR)
time Frame
On Average of (Cohort A:19.14, Cohort B: 12.39, Cohort D: 7.54, Cohort E: 5.44, Cohort F: 4.97, Cohort G: 12.30, Cohort H: 4.14, Cohort I: 8.79, Cohort J: 4.76, Cohort K: 6.51) Weeks
description
Duration of response is defined as time from the earliest date of documented response (PR or better) to the earliest date of disease progression per IMWG Uniform Response Criteria or death, whichever occurred first. Participants who do not have progression of disease or death will be censored on the last adequate response assessment date. Duration of response for responders will be summarized using Kaplan-Meier estimates by cohort and dose level as appropriate. Data will be collected and analyzed per Cohort Totals.
measure
Duration of Response
time Frame
On Average of (Cohort A:161.33, Cohort B: 63.74, Cohort D: 39.16, Cohort E: 89.56, Cohort F: 69.24, Cohort G: 80.93, Cohort H1: 77.11, Cohort H2: 42.71, Cohort I: 36.80, Cohort J: 92.36, Cohort K: 51.85) Weeks
description
Time from the first dose of investigational product (IP) to the first documentation of PD or death from any cause, whichever occurs first Data will be collected and analyzed per Cohort Totals.
measure
Progression Free Survival
time Frame
On Average of (Cohort A: 44.96, Cohort B: 32.79, Cohort D: 21.14, Cohort E: 53.74, Cohort F: 46.34, Cohort G: 63.26, Cohort H1: 58.10, Cohort H2: 22.11, Cohort I: 20.96, Cohort J: 86.21, Cohort K: 56.29) Weeks
description
Time from first dose of IP to death due to any cause Data will be collected and analyzed per Cohort Totals.
measure
Overall Survival for Cohort D, Cohort H2 and Cohort I
time Frame
On Average of (Cohort D: 81.14 Cohort H2: 91.54 Cohort I: 74.20)Weeks
description
Area under the plasma concentration time-curve. AUC over the dosing interval.
measure
Auc(Tau)
time Frame
From Cycle 1 Day 1 to Cycle 1 Day 15 (15 days)
description
Cmax is defined as maximum plasma concentration of the drug.
measure
Cmax
time Frame
From Cycle 1 Day 1 to Cycle 1 Day 15 (15 days)
description
Tmax is defined is the time to maximum plasma concentration.
measure
Tmax
time Frame
From Cycle 1 Day 1 to Cycle 1 Day 15 (15 days)

Full study description

brief Summary: 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.
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.

Source references

references

citation
Amatangelo M, Flynt E, Stong N, Ray P, Van Oekelen O, Wang M, Ortiz M, Maciag P, Peluso T, Parekh S, van de Donk NWCJ, Lonial S, Thakurta A. Pharmacodynamic changes in tumor and immune cells drive iberdomide's clinical mechanisms of activity in relapsed and refractory multiple myeloma. Cell Rep Med. 2024 Jun 18;5(6):101571. doi: 10.1016/j.xcrm.2024.101571. Epub 2024 May 21.
pmid
38776914
type
DERIVED
citation
Lonial S, Popat R, Hulin C, Jagannath S, Oriol A, Richardson PG, Facon T, Weisel K, Larsen JT, Minnema MC, Abdallah AO, Badros AZ, Knop S, Stadtmauer EA, Cheng Y, Amatangelo M, Chen M, Nguyen TV, Amin A, Peluso T, van de Donk NWCJ. Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1/2 trial. Lancet Haematol. 2022 Nov;9(11):e822-e832. doi: 10.1016/S2352-3026(22)00290-3. Epub 2022 Oct 6.
pmid
36209764
type
DERIVED