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)
37
Enrollment
1
Location
1
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 DiseaseIntervention/TreatmentPhase
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

ArmIntervention/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

    1. 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

    1. 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).

    2. 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.

    3. Time to progression [Up to 5 years post treatment]

    4. 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.

    5. 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:
    No
    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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Fred Hutch/University of Washington Cancer ConsortiumSeattleWashingtonUnited States98109

    Sponsors and Collaborators

    • University of Washington
    • Genzyme, a Sanofi Company

    Investigators

    • Principal Investigator: Andrew J. Cowan, Fred Hutch/University of Washington Cancer Consortium

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University of Washington
    ClinicalTrials.gov Identifier:
    NCT04883242
    Other Study ID Numbers:
    • RG1121154
    • NCI-2021-03406
    • 10690
    First Posted:
    May 12, 2021
    Last Update Posted:
    Mar 16, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 16, 2022