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

Sponsor

University of Washington (Other)

Overall Status

Recruiting

CT.gov ID

NCT04883242

Collaborator

Genzyme, a Sanofi Company (Industry)

Enrollment

Location

Arm

101.1

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

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 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.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Plasma Cell Myeloma Refractory Plasma Cell Myeloma	Drug: Carfilzomib Drug: Dexamethasone Biological: Isatuximab Drug: Pomalidomide	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

37 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 29, 2021

Anticipated Primary Completion Date :

Dec 31, 2029

Anticipated Study Completion Date :

Dec 31, 2029

Arms and Interventions

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: Carfilzomib Given IV Other Names: Kyprolis PR-171 Drug: Dexamethasone Given PO or IV Other Names: 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 Biological: Isatuximab Given IV Other Names: Hu 38SB19 Isatuximab-irfc SAR 650984 SAR650984 Sarclisa Drug: Pomalidomide Given PO Other Names: 4-Aminothalidomide Actimid CC-4047 Imnovid Pomalyst

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: Carfilzomib

Given IV

Other Names:

Kyprolis

PR-171

Drug: Dexamethasone

Given PO or IV

Other Names:

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

Biological: Isatuximab

Given IV

Other Names:

Hu 38SB19

Isatuximab-irfc

SAR 650984

SAR650984

Sarclisa

Drug: Pomalidomide

Given PO

Other Names:

4-Aminothalidomide

Actimid

CC-4047

Imnovid

Pomalyst

Outcome Measures

Primary Outcome Measures

Overall response rate [Up to 5 years post treatment]
Responses will be based on the International Myeloma Working Group criteria for response in multiple myeloma.

Secondary Outcome Measures

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]
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).
Overall survival [From the first study drug administration to death from any cause, assessed up to 5 years]
Kaplan-Meier methodology will be used to estimate the event-free curves.
Time to progression [Up to 5 years post treatment]
Incidence of adverse events [Up to 30 days post treatment]
Will be measured by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Rates of minimal residual disease negativity [Up to 5 years post treatment]
Measured by next-generation sequencing of immunoglobulin genes in the bone marrow.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with relapsed or refractory multiple myeloma, with 1 to 3 therapies
Must have received prior lenalidomide therapy and progressed on either a lenalidomide-containing regimen or lenalidomide maintenance (defined as a dose of 10-15 mg lenalidomide daily after induction regimen or maintenance)
Must have measurable disease, as defined by International Myeloma Working Group criteria, having one or more of the following:
Serum M protein >= 1.0 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)
Active hepatitis B, hepatitis C at time of screening
Subjects with active uncontrolled infection
Concurrent use of other anticancer agents or experimental treatments
Treatment with anti-CD38 monoclonal antibody therapy in the last 6 months