What side effects are associated with this type of intervention?

Common treatments for Multiple Myeloma, particularly those involving immunomodulatory drugs like lenalidomide and pomalidomide, and proteasome inhibitors like bortezomib, often result in side effects such as neutropenia, thrombocytopenia, anemia, gastrointestinal issues (nausea, diarrhea, constipation), peripheral neuropathy, fatigue, and increased risk of infections. Severe adverse events can include cardiac issues, hypertension, and secondary malignancies.

What prior FDA approvals exist?

The FDA has approved several treatments for Multiple Myeloma that are similar to CC-92480, a Cereblon E3 Ligase Modulator. Lenalidomide and pomalidomide, both of which modulate the Cereblon E3 ligase, have been approved for use in various stages of Multiple Myeloma. Lenalidomide is often used in combination with dexamethasone and other agents for both newly diagnosed and relapsed/refractory cases. Pomalidomide is typically used in patients who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. Other approved treatments include bortezomib, carfilzomib, and daratumumab, which are used in various combinations to enhance efficacy and manage relapsed or refractory Multiple Myeloma.

What other types of research exist?

Promising novel alternatives to CC-92480 for Multiple Myeloma patients include: 1) Carfilzomib, particularly in combination regimens such as KPd (carfilzomib, pomalidomide, dexamethasone), which has shown a 62% response rate and a median PFS of 10.3 months in phase 1/2 studies. 2) Ixazomib, an oral proteasome inhibitor, combined with dexamethasone, which has demonstrated durable responses and longer median time to vital organ deterioration or mortality compared to non-proteasome inhibitor regimens. 3) Venetoclax, especially in combination with low-dose cytarabine (LoDAC), which has shown superior outcomes compared to LoDAC monotherapy in AML and may be considered for Multiple Myeloma with specific genetic profiles.

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Proteasome Inhibitor

CC-92480 + Standard Treatments 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

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

For participants in Cohorts A, B, C, D, E, F, H, I, J, and K: documented diagnosis of multiple myeloma (MM) and measurable disease, documented disease progression during or after their last antimyeloma regimen, achieved a response (minimal response [MR] or better) to at least 1 prior treatment regimen

Must not have

Known central nervous system (CNS) involvement with myeloma

Plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclon), or clinically significant amyloidosis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called CC-92480 to see if it can help patients who are already getting standard treatments. The goal is to find out if adding this new drug can make their treatment work better.

Who is the study for?

This trial is for adults with Multiple Myeloma who've seen their cancer grow despite treatment and responded at least once to prior therapy. They should be fairly active and able to care for themselves (ECOG score of 0-2). People can't join if they have myeloma in the brain, took strong immune drugs recently, or have certain other blood disorders or uncontrolled conditions like high blood pressure.

What is being tested?

The study tests CC-92480 combined with standard myeloma treatments (like Isatuximab, Bortezomib) to see how safe it is and if it works against cancer that's come back or didn't respond well before. Participants will receive different combinations based on which group they're assigned to.

What are the potential side effects?

Possible side effects include reactions where the drug enters the body, changes in blood counts leading to increased infection risk or bleeding problems, fatigue, nausea, nerve damage causing pain or numbness, and potential heart issues.

Eligibility Criteria

Inclusion Criteria

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

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

Select...

I have multiple myeloma with measurable disease and it has worsened after treatment but I responded to at least one prior treatment.

Exclusion Criteria

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

Select...

My myeloma has spread to my brain or spinal cord.

Select...

I have a specific blood disorder such as plasma cell leukemia or Waldenstrom's macroglobulinemia.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

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

Treatment Details

Awards & Highlights

No Placebo-Only Group

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

Trial Design

15Treatment groups

Experimental Treatment

Group I: Subcohort E3: CC-92480 with daratumumab and dexamethasoneExperimental Treatment3 Interventions

Oral CC-92480 at RP2D administered over a 28-day cycle Either Intravenous (IV) DARA administered at a dose of 16 mg/kg or Subcutaneous (SC) DARA administered at a dose of 1800 mg over 3 to 5 minutes Oral/IV dexamethasone 40 mg weekly or 20 mg weekly for subjects older than 75 years or underweight administered over a 28-day cycle

Group II: Subcohort E2: CC-92480 with daratumumab and dexamethasoneExperimental Treatment3 Interventions

Oral CC-92480 at RP2D administered over a 21-day cycle from Cycle 1 to Cycle 8 and over a 28-day cycle from Cycle 9 onwards Either Intravenous (IV) DARA administered at a dose of 16 mg/kg or Subcutaneous (SC) DARA administered at a dose of 1800 mg over 3 to 5 minutes Oral/IV dexamethasone 40 mg weekly or 20 mg weekly for subjects older than 75 years or underweight, administered over a 21-day cycle from Cycle 1 to Cycle 8 and over a 28-day cycle from Cycle 9 onwards

Group III: Subcohort E1: CC-92480 with daratumumab and dexamethasoneExperimental Treatment3 Interventions

Oral CC-92480 at RP2D administered over a 28-day cycle Either IV DARA administered at a dose of 16 mg/kg or SC DARA administered at a dose of 1800 mg over 3 to 5 minutes Oral/IV dexamethasone 40 mg weekly or 20 mg weekly for subjects older than 75 years or underweight administered over a 28-day cycle

Group IV: Subcohort B3: CC-92480 with daratumumab and dexamethasoneExperimental Treatment3 Interventions

Oral CC-92480 at specified cohort B dose administered over a 28-day cycle Either Intravenous (IV) DARA administered at a dose of 16 mg/kg or Subcutaneous (SC) DARA administered at a dose of 1800 mg over 3 to 5 minutes Oral/IV dexamethasone 40 mg weekly or 20 mg weekly for subjects older than 75 years or underweight administered over a 28-day cycle

Group V: Subcohort B2: CC-92480 with daratumumab and dexamethasoneExperimental Treatment3 Interventions

Oral CC-92480 at specified cohort dose administered over a 21-day cycle from Cycle 1 to Cycle 8 and over a 28-day cycle from Cycle 9 onwards Either Intravenous (IV) DARA administered at a dose of 16 mg/kg or Subcutaneous (SC) DARA administered at a dose of 1800 mg over 3 to 5 minutes Oral/IV dexamethasone 40 mg weekly or 20 mg weekly for subjects older than 75 years or underweight, administered over a 21-day cycle from Cycle 1 to Cycle 8 and over a 28-day cycle from Cycle 9 onwards

Group VI: Subcohort B1: CC-92480 with daratumumab and dexamethasoneExperimental Treatment3 Interventions

Oral CC-92480 at specified cohort dose administered over a 28-day cycle Either Intravenous (IV) DARA administered at a dose of 16 mg/kg or Subcutaneous (SC) DARA administered at a dose of 1800 mg over 3 to 5 minutes Oral/IV dexamethasone 40 mg weekly or 20 mg weekly for subjects older than 75 years or underweight administered over a 28-day cycle

Group VII: Cohort K: CC-92480 with isatuximab and dexamethasoneExperimental Treatment3 Interventions

Group VIII: Cohort J: CC-92480 with elotuzumab and dexamethasoneExperimental Treatment3 Interventions

Group IX: Cohort I: CC-92480 with isatuximab and dexamethasoneExperimental Treatment3 Interventions

Group X: Cohort H: CC-92480 with elotuzumab and dexamethasoneExperimental Treatment3 Interventions

Group XI: Cohort G: CC-92480 with bortezomib and dexamethasoneExperimental Treatment3 Interventions

Oral CC-92480 at RP2D administered over a 21-day cycle Subcutaneous bortezomib 1.3 mg/m2 administered over a 21-day cycle up to Cycle 6 Oral dexamethasone 20 mg/day (≤ 75 years old) or 10 mg/day (> 75 years old) on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle up to Cycle 6

Group XII: Cohort F: CC-92480 with carfilzomib and dexamethasoneExperimental Treatment3 Interventions

Oral CC-92480 at RP2D administered over a 28-day cycle Intravenous (IV) carfilzomib 20 mg/m2 then 56 mg/m2 administered over a 28-day cycle Oral/IV dexamethasone 40 mg/day (20 mg/day for subjects > 75 years old) administered over a 28-day cycle

Group XIII: Cohort D: CC-92480 with bortezomib and dexamethasoneExperimental Treatment3 Interventions

Oral CC-92480 at RP2D administered over a 21-day cycle Subcutaneous bortezomib 1.3 mg/m2 administered over a 21-day cycle Oral dexamethasone 20 mg/day (≤ 75 years old) or 10 mg/day (> 75 years old) on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle in the first 8 cycles and on days 1, 2, 8 and 9 after Cycle 8

Group XIV: Cohort C: CC-92480 with carfilzomib and dexamethasoneExperimental Treatment3 Interventions

Oral CC-92480 at specified cohort C dose administered over a 28-day cycle Intravenous (IV) carfilzomib 20 mg/m2 then 56 mg/m2 administered over a 28-day cycle Oral/IV dexamethasone 40 mg/day (20 mg/day for subjects > 75 years old) administered over a 28-day cycle

Group XV: Cohort A: CC-92480 with bortezomib and dexamethasoneExperimental Treatment3 Interventions

Oral CC-92480 at specified cohort A dose administered over a 21-day cycle Subcutaneous bortezomib 1.3 mg/m2 administered over a 21-day cycle Oral dexamethasone 20 mg/day (≤ 75 years old) or 10 mg/day (> 75 years old) on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle in the first 8 cycles and on days 1, 2, 8 and 9 after Cycle 8

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

CC-92480

2018

Completed Phase 1

~150

Isatuximab

2016

Completed Phase 3

~370

Bortezomib

2005

Completed Phase 3

~1410

Dexamethasone

2007

Completed Phase 4

~2650

Daratumumab

2014

Completed Phase 3

~2000

Carfilzomib

2017

Completed Phase 3

~1430

Elotuzumab

2016

Completed Phase 3

~910

0 / 4Eligibility 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

Multiple Myeloma treatments often target specific cellular mechanisms to inhibit cancer cell growth and survival. Proteasome inhibitors (e.g., bortezomib) block the proteasome's function, leading to the accumulation of toxic proteins in cancer cells. Immunomodulatory drugs (IMiDs) like lenalidomide and pomalidomide, and newer CELMoDs like CC-92480, bind to cereblon, altering the activity of the E3 ubiquitin ligase complex, which results in the degradation of proteins essential for myeloma cell survival. Monoclonal antibodies (e.g., daratumumab) target specific antigens on myeloma cells, marking them for destruction by the immune system. These mechanisms are crucial as they provide multiple avenues to disrupt the cancer cells' lifecycle, offering hope for improved outcomes and prolonged survival for Multiple Myeloma patients.