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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04883242
Recruitment Status : Recruiting
First Posted : May 12, 2021
Last Update Posted : March 16, 2022
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
University of Washington

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : July 29, 2021
Estimated Primary Completion Date : December 31, 2029
Estimated Study Completion Date : December 31, 2029


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




Primary Outcome Measures :
  1. Overall response rate [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to 5 years post treatment ]
  4. Incidence of adverse events [ Time Frame: 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 [ Time Frame: Up to 5 years post treatment ]
    Measured by next-generation sequencing of immunoglobulin genes in the bone marrow.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 >= 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04883242


Contacts
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Contact: Andrew J. Cowan 206.667.4551 ajcowan@seattlecca.org

Locations
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United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Andrew J. Cowan    206-667-4551    ajcowan@seattlecca.org   
Principal Investigator: Andrew J. Cowan         
Sponsors and Collaborators
University of Washington
Genzyme, a Sanofi Company
Investigators
Layout table for investigator information
Principal Investigator: Andrew J. Cowan Fred Hutch/University of Washington Cancer Consortium
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Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT04883242    
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 )
First Posted: May 12, 2021    Key Record Dates
Last Update Posted: March 16, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Dexamethasone acetate
Pomalidomide
Ichthammol
BB 1101
Antibodies, Monoclonal
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal