Clinical Trial: NCT04883242 - My Cancer Genome

NCT04883242

Description:

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. 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. 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.

Related Conditions:

Multiple Myeloma

Recruiting Status:

Recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT04883242

Trial Eligibility

Document

Title

Brief Title: Isatuximab, Carfilzomib, Pomalidomide, and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma
Official Title: Isatuximab, Carfilzomib, Pomalidomide, and Dexamethasone (Isa-KPd) for Patients With Relapsed/Refractory Multiple Myeloma

Clinical Trial IDs

ORG STUDY ID: RG1121154
SECONDARY ID: NCI-2021-03406
SECONDARY ID: 10690
NCT ID: NCT04883242

Conditions

Recurrent Plasma Cell Myeloma
Refractory Plasma Cell Myeloma

Interventions

Drug	Synonyms	Arms
Carfilzomib	Kyprolis, PR-171	Treatment (isatuximab, carfilzomib, pomalidomide, steroid)
Dexamethasone	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)
Isatuximab	Hu 38SB19, Isatuximab-irfc, SAR 650984, SAR650984, Sarclisa	Treatment (isatuximab, carfilzomib, pomalidomide, steroid)
Pomalidomide	4-Aminothalidomide, Actimid, CC-4047, Imnovid, Pomalyst	Treatment (isatuximab, carfilzomib, pomalidomide, steroid)

Purpose

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.

Trial Arms

Name	Type	Description	Interventions
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.	Carfilzomib Dexamethasone Isatuximab Pomalidomide

Eligibility Criteria

        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 >= 2cm)

               -  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

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Overall response rate
Time Frame:	Up to 5 years post treatment
Safety Issue:
Description:	Responses will be based on the International Myeloma Working Group criteria for response in multiple myeloma.

Secondary Outcome Measures

Measure:	Progression-free survival (PFS)
Time Frame:	From first study drug administration to the first occurrence of disease progression or death from any cause, assessed up to 5 years
Safety Issue:
Description:	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).

Measure:	Overall survival
Time Frame:	From the first study drug administration to death from any cause, assessed up to 5 years
Safety Issue:
Description:	Kaplan-Meier methodology will be used to estimate the event-free curves.

Measure:	Time to progression
Time Frame:	Up to 5 years post treatment
Safety Issue:
Description:

Measure:	Incidence of adverse events
Time Frame:	Up to 30 days post treatment
Safety Issue:
Description:	Will be measured by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Measure:	Rates of minimal residual disease negativity
Time Frame:	Up to 5 years post treatment
Safety Issue:
Description:	Measured by next-generation sequencing of immunoglobulin genes in the bone marrow.

Details

Phase:	Phase 2
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	University of Washington

Last Updated

August 3, 2021

Clinical Trials /

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