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

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 mutliple 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: Recruiting
• Conditions: Refractory Multiple Myeloma; Recurrent Multiple Myeloma
• Intervention / Treatment: Drug: Dexamethasone; Drug: Pomalidomide; Biological: Isatuximab; Drug: Carfilzomib

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.

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

• Study Type: Interventional
• Enrollment (Estimated): 37
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Andrew J. Cowan; Phone Number: 206.667.4551; Email: ajcowan@seattlecca.org

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutch/University of Washington Cancer Consortium
      • Principal Investigator: Andrew J. Cowan
      • Contact: Andrew J. Cowan; Phone Number: 206-667-4551; Email: ajcowan@seattlecca.org

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 (with the exception of non-melanoma skin cancer, curatively treated localized prostate cancer, curatively treated superficial bladder cancer and cervical carcinoma in site on biopsy or a squamous intraepithelial lesion on papanicolaou [PAP] smear)
• 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
• Treatment with anti-CD38 monoclonal antibody therapy in the last 90 days

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.

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; 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

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

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: Genzyme, a Sanofi Company
• Investigators: Principal Investigator: Andrew J. Cowan, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2021
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029

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 (Estimated): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dermatologic Agents; Anti-Bacterial Agents; Leprostatic Agents; Dexamethasone; Dexamethasone acetate; BB 1101; Thalidomide; Pomalidomide; Antibodies, Monoclonal; Ichthammol
• 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