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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04883242
Other study ID # RG1121154
Secondary ID NCI-2021-0340610
Status Recruiting
Phase Phase 2
First received
Last updated
Start date July 29, 2021
Est. completion date December 31, 2029

Study information

Verified date May 2024
Source University of Washington
Contact Andrew J. Cowan
Phone 206.667.4551
Email ajcowan@fredhutch.org
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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. All patients undergo bone marrow aspirate and biopsy during screening, skeletal x-ray, computed tomography (CT), positron emission tomography (PET)-CT, or magnetic resonance imaging (MRI), bone marrow and blood sample collection throughout the study. After completion of study treatment, patients are followed up at 30 days, then for up to 5 years.


Recruitment information / eligibility

Status Recruiting
Enrollment 37
Est. completion date December 31, 2029
Est. primary completion date December 31, 2029
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 - However, the following diagnoses are eligible for inclusion: non-melanoma skin cancer, localized prostate cancer, superficial bladder cancer, cervical carcinoma in situ, on biopsy or any prior malignancy with an estimated > 90% 1-year cure rate per sponsor-investigator - 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 Design


Intervention

Drug:
Carfilzomib
Given IV
Dexamethasone
Given PO or IV
Biological:
Isatuximab
Given IV
Drug:
Pomalidomide
Given PO
Procedure:
Bone Marrow Biopsy
Undergo bone marrow biopsy
Bone Marrow Aspiration
Undergo bone marrow aspiration
Skeletal Survey X-Ray
Undergo skeletal x-ray
Computed Tomography
Undergo CT
Positron Emission Tomography
Undergo PET-CT
Magnetic Resonance Imaging
Undergo MRI

Locations

Country Name City State
United States Fred Hutch/University of Washington Cancer Consortium Seattle Washington

Sponsors (2)

Lead Sponsor Collaborator
University of Washington Genzyme, a Sanofi Company

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 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
Secondary 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
Secondary Time to progression Up to 5 years post treatment
Secondary 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
Secondary Rates of minimal residual disease negativity Measured by next-generation sequencing of immunoglobulin genes in the bone marrow. Up to 5 years post treatment
See also
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Completed NCT01775553 - Study of High Dose Carfilzomib in Multiple Myeloma Patients Who Have Progressed On Standard Dose Carfilzomib Phase 2
Completed NCT01212952 - Pomalidomide, Bortezomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma Phase 1/Phase 2
Terminated NCT01078441 - Bortezomib, Liposomal Doxorubicin Hydrochloride, Dexamethasone, and Cyclophosphamide in Treating Patients With Multiple Myeloma That Relapsed After Autologous Stem Cell Transplant Phase 2
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Completed NCT00514137 - Sunitinib in Treating Patients With Relapsed Multiple Myeloma Phase 2
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