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

NCT04883242 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: RG1121154NCI-2021-0340610690
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the effect of isatuximab, carfilzomib, pomalidomide, and dexamethasone 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 proteins needed for cell growth. Pomalidomide may help shrink or slow the growth of multiple myeloma. Anti-inflammatory drugs, such as dexamethasone lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Giving isatuximab, carfilzomib, pomalidomide, and dexamethasone may kill more cancer cells.

Conditions

Recurrent Multiple Myeloma; Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  Responses will be based on the International Myeloma Working Group criteria for response in multiple myeloma.

  Up to 5 years post treatment

Secondary Outcomes (6)

• Progression-free survival (PFS)

  From first study drug administration to the first occurrence of disease progression or death from any cause, assessed up to 5 years

• Overall survival

  From the first study drug administration to death from any cause, assessed up to 5 years

• Duration of response

  Up to 5 years post treatment

• Time to progression

  Up to 5 years post treatment

• Incidence of adverse events

  Up to 30 days post treatment

Study Arms (1)

Treatment (isatuximab, carfilzomib, pomalidomide, steroid)

EXPERIMENTAL

INDUCTION: Patients receive isatuximab IV on days 1, 8, 15, and 22 of cycle 1 and days 1 and 15 of subsequent cycles carfilzomib IV over 30 minutes on days 1, 8, and 15, pomalidomide PO QD on days 1-21, and dexamethasone PO or IV on days 1,8, 15, and 22. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive isatuximab IV days 1 and 15, carfilzomib IV over 30 minutes on days 1 and 15, pomalidomide PO QD on days 1-21, and dexamethasone PO or IV on days 1, 8, 15, and 22. Cycles repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity. All patients undergo bone marrow aspirate and biopsy during screening, skeletal x-ray, CT, PET-CT, or MRI, bone marrow and blood sample collection throughout the study.

Drug: Carfilzomib; Drug: Dexamethasone; Biological: Isatuximab; Drug: Pomalidomide; Procedure: Bone Marrow Biopsy; Procedure: Bone Marrow Aspiration; Procedure: Skeletal Survey X-Ray; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Procedure: Magnetic Resonance Imaging

Interventions

Isatuximab BIOLOGICAL

Given IV

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

Treatment (isatuximab, carfilzomib, pomalidomide, steroid)

Pomalidomide DRUG

Given PO

Also known as: 4-Aminothalidomide, Actimid, CC-4047, Imnovid, Pomalyst, CC4047

Treatment (isatuximab, carfilzomib, pomalidomide, steroid)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Treatment (isatuximab, carfilzomib, pomalidomide, steroid)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Treatment (isatuximab, carfilzomib, pomalidomide, steroid)

Skeletal Survey X-Ray PROCEDURE

Undergo skeletal x-ray

Treatment (isatuximab, carfilzomib, pomalidomide, steroid)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT Scan, Computed Axial Tomography

Treatment (isatuximab, carfilzomib, pomalidomide, steroid)

Positron Emission Tomography PROCEDURE

Undergo PET-CT

Also known as: PET scan

Treatment (isatuximab, carfilzomib, pomalidomide, steroid)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: MRI

Treatment (isatuximab, carfilzomib, pomalidomide, steroid)

Carfilzomib DRUG

Given IV

Also known as: Kyprolis, PR-171, Carfilnat, CFZ

Treatment (isatuximab, carfilzomib, pomalidomide, steroid)

Dexamethasone DRUG

Given PO or IV

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Treatment (isatuximab, carfilzomib, pomalidomide, steroid)

Eligibility Criteria

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

You may qualify if:

• Patients with relapsed or refractory multiple myeloma, with \>= 1 prior therapy
• Must have received prior lenalidomide therapy
• Must have measurable disease, as defined by International Myeloma Working Group criteria, having one or more of the following:
• Serum M protein \>= 0.5 g/dL
• Urine M protein \>= 200 mg/24 hours
• Involved serum free light chain level \>= 10 mg/dL with abnormal kappa/lambda ratio
• Measurable biopsy-proven plasmacytomas (\>= 1 lesion has a single diameter \>= 2 cm)
• Bone marrow plasma cells \>= 30%
• Age 18 years and older, and have the capacity to give informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Subjects should have resolution of any toxicities from prior therapy to grade =\< 1 or baseline prior to enrollment (with the exception of peripheral neuropathy)
• Subjects are required to have grade =\< 2 peripheral neuropathy to enroll
• Prior autologous stem cell transplant is allowed; patients must be \>= 6 months post- autologous stem cell transplantation to enroll
• Estimated glomerular filtration rate (eGFR) \>= 20 ml/min
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x upper limit of normal (ULN)

You may not qualify if:

• History of clinically significant cardiovascular disease, including congestive heart failure New York Heart Association (NYHA) class 3-4, symptomatic ischemia, left ventricular ejection fraction \< 40%, uncontrolled conduction abnormalities, myocardial infarction in last 6 months
• Uncontrolled hypertension as determined by the principal investigator (PI) or designee
• Active plasma cell leukemia or systemic amyloid light-chain (AL) amyloidosis
• History of another primary malignancy that has not been in remission for at least 1 year
• For patients with chronic hepatitis B viral infection, the hepatitis B virus (HBV) polymerase chain reaction (PCR) must be undetectable on suppressive therapy
• Patients with a history of Hepatitis C viral infection must have been treated and cured. For patients on treatment for hepatitis C, they are eligible if they have an undetectable hepatitis C virus (HCV) viral load
• Subjects with active uncontrolled infection
• Concurrent use of other anticancer agents or experimental treatments

Sponsors & Collaborators

• Genzyme, a Sanofi Company: collaborator
• University of Washington: lead

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; isatuximab; pomalidomide; Magnetic Resonance Spectroscopy

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

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Rahul Banerjee, MD

  Fred Hutch/University of Washington Cancer Consortium

  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: SPONSOR

Study Record Dates

• First Submitted: May 6, 2021
• First Posted: May 12, 2021
• Study Start: July 29, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2031
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)