What side effects are associated with this type of intervention?

Common treatments for Multiple Myeloma, such as those involving CC-220, dexamethasone, daratumumab, bortezomib, and carfilzomib, are associated with several side effects. Dexamethasone can cause hyperglycemia, insomnia, and increased risk of infections. Daratumumab may lead to infusion-related reactions and respiratory issues. Bortezomib is known for causing peripheral neuropathy, gastrointestinal disturbances, and increased risk of herpes zoster. Carfilzomib can result in cardiovascular complications, fatigue, and dyspnea. These treatments, while effective, require careful management of their side effects to ensure patient safety and quality of life.

What prior FDA approvals exist?

The FDA has approved several treatments for Multiple Myeloma that involve immune modulation and targeting myeloma cells. Daratumumab, a monoclonal antibody, has been approved for use both as a monotherapy and in combination with other drugs like bortezomib, lenalidomide, and dexamethasone. Bortezomib, a proteasome inhibitor, is often used in combination with dexamethasone and other agents. Lenalidomide, an immunomodulatory drug, is also frequently used in combination regimens. These treatments aim to enhance the immune system's ability to target and destroy myeloma cells, similar to the investigational drug CC-220 being studied in the trial.

What other types of research exist?

Promising novel alternatives to CC-220 for Multiple Myeloma patients include: 1) BCMA-targeted therapies such as CAR-T cell therapy (e.g., idecabtagene vicleucel) and bispecific antibodies (e.g., teclistamab); 2) Selinexor, a selective inhibitor of nuclear export; 3) Venetoclax, particularly for patients with t(11;14) translocation; 4) Newer proteasome inhibitors like ixazomib; and 5) Monoclonal antibodies such as isatuximab. These therapies have shown significant efficacy in clinical trials and offer new mechanisms of action for targeting Multiple Myeloma cells.

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Immunomodulatory Agent

CC-220 Combination Therapy for Multiple Myeloma

Phase 1 & 2

Waitlist Available

Research Sponsored by Celgene

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Must not have

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up approximately 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new drug, CC-220, alone and with other drugs for patients with multiple myeloma who haven't responded to other treatments or are newly diagnosed. The drugs work by controlling cancer cell growth and killing cancer cells through different mechanisms.

Who is the study for?

This trial is for adults with Multiple Myeloma, either newly diagnosed and untreated (NDMM) or those whose disease has returned after treatment (RRMM). They must be in fairly good health overall, as indicated by an ECOG score of 0-2. People who have had other cancers within the last 5 years or have a significant medical condition that could interfere with the study cannot participate.

What is being tested?

The trial is testing different doses and combinations of a drug called CC-220 alone or with other treatments like Dexamethasone, Daratumumab, Bortezomib, and Carfilzomib. It's divided into two parts: finding the right dose and then expanding to more patients at that dose to see how well it works for both new and returning cases of Multiple Myeloma.

What are the potential side effects?

Possible side effects include reactions where the drugs are given, changes in blood counts leading to increased infection risk or bleeding problems, fatigue, nausea, nerve damage causing pain or weakness especially in hands and feet (neuropathy), liver issues, and potential heart complications.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with multiple myeloma and have not received any treatment.

Select...

I am not planned for or eligible for stem cell transplant as my initial treatment.

Select...

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

My multiple myeloma does not produce detectable levels of M protein.

Select...

I have been cancer-free for over 5 years, except for multiple myeloma or certain non-invasive cancers.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ approximately 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~approximately 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and approximately 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Establish Recommended Phase 2 doses (RP2Ds) of CC-220 as monotherapy and in combination with other treatment

Establish maximum tolerated doses (MTDs) of CC-220 as monotherapy and in combination with other treatment

Overall response rate (ORR) of CC-220 in combination with Dexamethasone (DEX) in Cohort D

Secondary study objectives

Adverse Events (AEs)

Duration of Response (DOR)

Overall Survival (OS) in Part 2 relapsed and refractory multiple myeloma (RRMM) cohorts

+4 more

Side effects data

From 2021 Phase 2 trial • 289 Patients • NCT03161483

20%

Neutropenia

19%

Urinary tract infection

19%

Upper respiratory tract infection

12%

Leukopenia

12%

Nasopharyngitis

10%

Diarrhoea

10%

Influenza

Anaemia

Nausea

Bronchitis

Back pain

Hypertension

Sinusitis

Lymphopenia

Pharyngitis

Pruritus

Headache

Pneumonia

Vomiting

Pyrexia

COVID-19

Gastroenteritis

Hypertriglyceridaemia

Limb injury

Oral herpes

Dyspnoea

Tinnitus

Abscess limb

Joint injury

Forearm fracture

Radius fracture

Polyneuropathy

Proteinuria

Chronic obstructive pulmonary disease

Oropharyngeal pain

Cellulitis

Gastroenteritis viral

Influenza like illness

Lower respiratory tract infection

Joint instability

Epistaxis

Abdominal pain upper

COVID-19 pneumonia

Uterine haemorrhage

Hypoaesthesia

100%

80%

60%

40%

20%

Study treatment Arm

0.45mg QD

Active Treatment Phase 0.30mg Following Placebo

0.15mg QD

0.30mg QD

Active Treatment Phase 0.45mg Following Placebo

Placebo

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

12Treatment groups

Experimental Treatment

Group I: Cohort K: CC-220 with DEX and DARA in NDMM and not autologous stem cell transplant eligible - Part 2Experimental Treatment3 Interventions

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.

Group II: Cohort J2: CC-220 in combination with DEX and BTZ in NDMM - Part 2Experimental Treatment3 Interventions

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.

Group III: Cohort J1: CC-220 in combination with DEX and BTZ in NDMM - Part 2Experimental Treatment3 Interventions

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.

Group IV: Cohort I: CC-220 in combination with DEX in post BCMA RRMM - Part 2Experimental Treatment2 Interventions

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.

Group V: Cohort G2 - CC-220 in combination with CFZ and DEX - Part 1Experimental Treatment3 Interventions

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.

Group VI: Cohort G1: CC-220 in combination with CFZ and DEX - Part 1Experimental Treatment3 Interventions

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

Group VII: Cohort F: CC-220 with DEX and bortezomib - Part 1Experimental Treatment3 Interventions

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.

Group VIII: Cohort E: CC-220 with DEX and daratumumab (DARA) - Part 1Experimental Treatment3 Interventions

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.

Group IX: Cohort D: CC-220 in combination with Dexamethasone - Part 2Experimental Treatment2 Interventions

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

Group X: Cohort C: CC-220 Monotherapy in RRMM - Part 2Experimental Treatment1 Intervention

CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.

Group XI: Cohort B: CC-220 in combination with Dexamethasone (DEX) - Part 1Experimental Treatment2 Interventions

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.

Group XII: Cohort A: CC-220 Monotherapy - Part 1Experimental Treatment1 Intervention

Oral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

CC-220

2016

Completed Phase 2

~620

Dexamethasone

2007

Completed Phase 4

~2650

Carfilzomib

2017

Completed Phase 3

~1430

Bortezomib

2005

Completed Phase 3

~1410

Daratumumab

2014

Completed Phase 3

~2000

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Multiple Myeloma include immune modulators and agents that target myeloma cells directly. Dexamethasone is a corticosteroid that reduces inflammation and suppresses the immune system, helping to control myeloma cell growth. Daratumumab is a monoclonal antibody that targets CD38 on myeloma cells, leading to their destruction by the immune system. Bortezomib and carfilzomib are proteasome inhibitors that disrupt protein degradation in myeloma cells, causing cell death. These treatments are crucial for Multiple Myeloma patients as they target the disease through different mechanisms, improving treatment efficacy and patient outcomes.

The immune microenvironment of myeloma.