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

Isa-CAPED MM: Isatuximab, Carfilzomib, Pomalidomide, and Dexamethasone (Isa-KPd) for Patients With Relapsed/Refractory Multiple Myeloma

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Refractory Multiple Myeloma; Recurrent Multiple Myeloma
• Intervention / Treatment: Procedure: Magnetic Resonance Imaging; Procedure: Computed Tomography; Drug: Dexamethasone; Drug: Pomalidomide; Procedure: Bone Marrow Aspiration; Biological: Isatuximab; Drug: Carfilzomib; Procedure: Positron Emission Tomography; Procedure: Bone Marrow Biopsy; Procedure: Skeletal Survey X-Ray

Detailed Description

OUTLINE:

INDUCTION: Patients receive isatuximab intravenously (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 orally (PO) once daily (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, computed tomography (CT), positron emission tomography (PET)-CT, or magnetic resonance imaging (MRI), bone marrow and blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 30 days, then for up to 5 years.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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)
• Total bilirubin =< 2 x ULN
• Absolute neutrophil count (ANC) >= 1,000/uL
• Platelets >= 50,000/uL
• Hemoglobin >= 8 g/dL
• Growth factor use or transfusions may be used to meet the eligibility requirement for ANC, platelets, and hemoglobin
• Female patients of childbearing potential and male patients must agree to use 2 effective forms of contraception or continuously abstain from heterosexual intercourse during the period of therapy, and for 6 months after discontinuation of study treatment for females and 3 months after discontinuation of study treatment for males

Exclusion Criteria:

• 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

  • However, the following diagnoses are eligible for inclusion: non-melanoma skin cancer, localized prostate cancer, superficial bladder cancer, cervical carcinoma in situ, on biopsy or any prior malignancy with an estimated > 90% 1-year cure rate per sponsor-investigator
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (isatuximab, carfilzomib, pomalidomide, steroid); 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.

Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Procedure: Computed Tomography; Undergo CT; Other Names: CAT Scan; Computed Axial Tomography; Drug: Dexamethasone; Given PO or IV; Other Names: Decadron; Hemady; 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 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; Hexadecadrol; Hexadrol; Lokalison-F; Loverine; Methylfluorprednisolone; Millicorten; Mymethasone; Orgadrone; Spersadex; TaperDex; Visumetazone; ZoDex; Drug: Pomalidomide; Given PO; Other Names: Pomalyst; Imnovid; 4-Aminothalidomide; Actimid; CC-4047; CC4047; Procedure: Bone Marrow Aspiration; Undergo bone marrow aspiration; Biological: Isatuximab; Given IV; Other Names: Hu 38SB19; SAR 650984; SAR650984; Sarclisa; Isatuximab-irfc; SAR-650984; Drug: Carfilzomib; Given IV; Other Names: Kyprolis; PR-171; CFZ; Carfilnat; Procedure: Positron Emission Tomography; Undergo PET-CT; Other Names: PET scan; Procedure: Bone Marrow Biopsy; Undergo bone marrow biopsy; Procedure: Skeletal Survey X-Ray; Undergo skeletal x-ray

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS will be calculated using assessments by investigators. Kaplan-Meier methodology will be used to estimate event-free curves and corresponding quartiles (including the median).	From first study drug administration to the first occurrence of disease progression or death from any cause, assessed up to 5 years
Overall survival	Kaplan-Meier methodology will be used to estimate the event-free curves.	From the first study drug administration to death from any cause, assessed up to 5 years
Time to progression		Up to 5 years post treatment
Incidence of adverse events	Will be measured by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.	Up to 30 days post treatment
Rates of minimal residual disease negativity	Measured by next-generation sequencing of immunoglobulin genes in the bone marrow.	Up to 5 years post treatment
Duration of response		Up to 5 years post treatment

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: Genzyme, a Sanofi Company
• Investigators: Principal Investigator: Rahul Banerjee, MD, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: May 6, 2021
• First Submitted That Met QC Criteria: May 6, 2021
• First Posted (Actual): May 12, 2021

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Sulfur Compounds; Organic Chemicals; Investigative Techniques; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Benzene Derivatives; Chemistry Techniques, Analytical; Sulfonic Acids; Sulfur Acids; Spectrum Analysis; Pregnadienetriols; Benzenesulfonates; Arylsulfonates; Arylsulfonic Acids; Dexamethasone; Calcium Dobesilate; Magnetic Resonance Spectroscopy; carfilzomib; pomalidomide; dexamethasone 21-phosphate; isatuximab; auricularum; dexamethasone acetate
• Other Study ID Numbers: RG1121154; NCI-2021-03406 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 10690 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No