Isatuximab, Carfilzomib, and Pomalidomide for the Treatment of Relapsed or Refractory Multiple Myeloma

NCT04850599 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: STUDY00021808NCI-2021-02297
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the effect of isatuximab, carfilzomib, and pomalidomide in treating patients with multiple myeloma that has come back (relapsed) or does not respond to treatment (refractory). Isatuximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as pomalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving isatuximab, carfilzomib, and pomalidomide may help treat patients with multiple myeloma.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  Defined as the proportion of participants who achieve a response \>= partial response (PR) (i.e., PR, very good partial response, complete response, or stringent complete response) according to International Myeloma Working Group criteria. ORR will be measured from start of study treatment (i.e., cycle 1 day 1) to the earliest of the following events: end of cycle 4, start of new anti-myeloma therapy, documented disease progression, or death. Will be evaluated using the response-evaluable analysis set. A point estimate and exact 95% confidence interval will be provided.

  Up to end of cycle 4 (each cycles is 28 days), disease progression, start of new anti-myeloma therapy, or death (whichever occurs first)

Secondary Outcomes (5)

• Incidence of grade > 2 toxicities

  Up to 30 days after discontinuing study treatment

• Duration of response (DOR)

  From initial disease response (>= PR) until disease progression, disease-related death, death from other cause (competing risk), or end of follow-up (censored), whichever occurs first, assessed up to 24 months

• Time to next treatment

  From start of study regimen until start of new anti-myeloma therapy, death from any cause before new therapy, or end of follow-up (censored), whichever occurs first, assessed up to 24 months

• Progression-free survival

  From start of study treatment until disease progression, death, or end of follow-up (censored), whichever occurs first, assessed up to 24 months

• Overall survival

  From start of study treatment until death or last known alive (censored), assessed up to 24 months

Other Outcomes (1)

• Frequency of minimal residual disease negative remissions at time of complete response

  First post-baseline bone marrow or aspirate until last standard of care bone marrow biopsy on study (including follow-up), assessed up to 24 months

Study Arms (1)

Treatment (isatuximab, carfilzomib, pomalidomide)

EXPERIMENTAL

Patients receive isatuximab IV over 30-60 minutes on days 1, 8, 15, and 22 of cycle 1, and days 1 and 15 of subsequent cycles, carfilzomib IV over 10 to 30 minutes on days 1, 8, 15, and pomalidomide PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Carfilzomib; Biological: Isatuximab; Drug: Pomalidomide

Interventions

Carfilzomib DRUG

Given IV

Also known as: Kyprolis, PR-171

Treatment (isatuximab, carfilzomib, pomalidomide)

Isatuximab BIOLOGICAL

Given IV

Also known as: Hu 38SB19, Isatuximab-irfc, SAR 650984, SAR650984, Sarclisa

Treatment (isatuximab, carfilzomib, pomalidomide)

Pomalidomide DRUG

Given PO

Also known as: 4-Aminothalidomide, Actimid, CC-4047, Imnovid, Pomalyst

Treatment (isatuximab, carfilzomib, pomalidomide)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant or legally authorized representative (LAR) must provide written informed consent before any study specific procedures or interventions are performed
• Participants must be \>= 18 years of age
• Histologically or cytologically confirmed diagnosis of multiple myeloma (MM) as defined by 2016 International Myeloma Working Group (IMWG) criteria
• Relapsed or relapsed and refractory (R/R) MM, as defined by International Myeloma Working Group (IMWG) criteria:
• Relapsed myeloma: Previously treated myeloma that has progressed and is neither "refractory myeloma" nor "relapsed-and-refractory myeloma"
• Refractory myeloma: Nonresponsive myeloma while on primary or salvage therapy, or progresses within 60 days of last therapy. Nonresponsive disease is defined as failure to achieve minimal response (MR) or better, achieved with any therapy. Cases in which there is no significant change in M protein and no evidence of clinical progression, are included, as well those cases that progress in disease course
• Primary refractory myeloma: Disease that is nonresponsive in patients who have never achieved a minimal response or better with any therapy
• Relapsed-and-refractory myeloma: Disease that is nonresponsive while on salvage therapy or progresses with 60 days of last therapy after achieving MR or better previously before progressing
• Participant has received at least 1 line of prior therapy.
• Prior exposure to proteasome inhibitor is permitted. The washout period is 2 weeks (14 days) prior to start of study treatment (cycle 1 day 1 \[C1D1\])
• Prior exposure to immunomodulatory imide drug (IMiD) therapy (lenalidomide, pomalidomide, or thalidomide) is permitted. The washout period is 2 weeks (14 days) prior to start of study treatment (C1D1)
• Prior treatment with anti-CD38 therapy (e.g., daratumumab) is permitted. The washout period is 6 months prior to start of study treatment (C1D1)
• Measurable disease with at least one of the following:
• Monoclonal immunoglobulin spike on serum protein electrophoresis of \>= 0.5 g/dL
• Urine monoclonal immunoglobulin spike of \>= 200 mg/24 hours

You may not qualify if:

• Waldenstrom macroglobulinemia
• Multiple myeloma of immunoglobulin M (IgM) subtype
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Plasma cell leukemia (\> 2.0 x 10\^9/L circulating plasma cells by standard differential)
• Myelodysplastic syndrome
• Participants with known or suspected amyloidosis
• Individuals that are refractory to prior treatment with either carfilzomib or pomalidomide
• Intolerance leading to discontinuation of either carfilzomib or pomalidomide
• Prior allogeneic stem cell transplant
• Second malignancy requiring concurrent treatment or those with non-hematological malignancies (except non-melanoma skin cancers). Cancer treated with curative intent \< 5 years previously will not be allowed unless approved by the principal investigator (PI). Cancer treated with curative intent \> 5 years previously is allowed
• Any known allergies or hypersensitivity to isatuximab or other monoclonal antibody therapies and required premedications
• Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
• Hypersensitivity to any of the components of study therapy that is not amenable to premedication with steroids and H2 blockers
• Participant has received prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, of the first dose of study medication. Wash-out period of prior anti-CD38 therapy (e.g. Daratumumab) is 6 months before first dose of study medication.
• Exception: Emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 mg per day for a maximum of 4 days) before treatment is not a barrier to eligibility

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Oregon Health and Science University: collaborator
• Sanofi: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; isatuximab; pomalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Rebecca W Silbermann

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 14, 2021
• First Posted: April 20, 2021
• Study Start: June 14, 2022
• Primary Completion (Estimated): October 15, 2026
• Study Completion (Estimated): February 21, 2029
• Last Updated: December 18, 2025

Record last verified: 2025-12

Locations

US (1)