Status and phase
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About
This research study is investigating the safety and effectiveness of using combination of isatuximab, lenalidomide and dexamethasone for the treatment of newly diagnosed multiple myeloma (MM). The study team will use lower doses than is currently standard for these drugs. Lower doses will be used to avoid or possibly reduce any unwanted side effects commonly associated with these drugs. Using lower doses of the combination isatuximab, lenalidomide and dexamethasone, has not been approved by the Food and Drug Administration (FDA) for the treatment of newly diagnosed MM.
Full description
This study aims to determine the optimal treatment regimen for older and/or otherwise toxicity-vulnerable patients with newly diagnosed multiple myeloma (NDMM) who cannot receive approved standard therapy. As a result, this Phase II trial of isatuximab, lenalidomide, and dexamethasone (Isa-Rd) selectively enroll much older and/or otherwise highly toxicity-vulnerable participants. Furthermore, the safety and effectiveness of isatuximab when used in combination with lenalidomide and dexamethasone at lower doses will be evaluated. It is expected that using this combination at lower doses, may help patients achieve a better response while causing fewer or less severe side effects.
All participants on the trial will also be evaluated by Cancer and Aging Research Group Geriatric Assessments (CARG-GA) and patient-reported outcome (PRO) measures of quality of life (QOL). "Geriatric assessment" will be referred to as "global assessment" for study purposes, to reflect the fact that younger participants will likely participate in the study. Optional correlative blood samples will be collected to study biomarkers of aging and frailty with a focus on both the relation to isatuximab specifically, as well as treatment response and risk for intolerability.
Duration of Therapy:
The length of study participation will depend on the response to the treatment, and it may last approximately 2 years. Participants will receive isatuximab for two years, and then isatuximab will be discontinued. Dexamethasone administration will occur weekly for the first eight cycles. Lenalidomide will be continued as maintenance until disease progression or unacceptable toxicity.
In the absence of treatment delays due to adverse events, treatment should continue until:
Duration of Follow Up:
All participants (including those withdrawn for AE (Adverse Event) will be followed after removal from study treatment until death or full subject withdrawal from the study for other reasons. Participants removed from study treatment for unacceptable AEs will be followed for resolution or stabilization of the adverse event(s).
Enrollment
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Inclusion and exclusion criteria
Subject Eligibility In order to participate in this study a subject must meet all of the eligibility criteria outlined below.
Inclusion Criteria
Written informed consent obtained to participate in the study and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information (PHI). Consent must be obtained before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
Willing and able to adhere to the study visit schedule and other protocol requirements based on the judgement of the investigator or protocol designee.
Predicted high risk for severe toxicity from intensive induction regimens, such as standard (full-dose) Bortezomib, cyclophosphamide, dexamethasone (VCD), lenalidomide, bortezomib, and dexamethasone (RVD), or lenalidomide and weekly dexamethasone (Rd) as each regimen was published. (Such regimens often use, for example, twice-weekly bortezomib or lenalidomide at 25 mg.) High-risk is defined as one of the following:
Subjects qualifying for enrollment by criterion C should be discussed with the Medical Monitor before enrollment, to ensure uniform application of this criterion across participating sites.
Measurable MM diagnosed according to the following standard criteria. Criteria A and B must be met, in addition to C and/or D:
Monoclonal plasma cells in bone marrow ≥ 10% and/or presence of biopsy-proven plasmacytoma
Monoclonal protein (M-protein) present in serum and/or urine, defined as serum M-protein of ≥ 1 g/dL (0.5 g/dL for Immunoglobulin A (IgA) MM) OR urine M-protein of ≥ 200 mg/24 hours. Subjects lacking an M-protein meeting those criteria must have a serum free light chain assay with an involved light chain ≥ 10 mg/dL (100 mg/L) and an abnormal serum free light chain ratio.
One or more MM-related organ dysfunction findings such as hypercalcemia, renal insufficiency, anemia, and bone lesions (CRAB) criteria listed below:
Myeloma-related biomarker of malignancy (1 or more should be fulfilled):
No prior systemic anti-myeloma therapy lasting more than 28 days (generally one cycle). Any prior therapy must be completed a minimum of 14 days before starting study drugs.
Subjects who require radiotherapy (which must be localized in its field size) may be treated during screening but initiating study therapy should be deferred until the radiotherapy is completed and 14 days have elapsed since the last date of radiotherapy.
Demonstrate adequate organ function and laboratory values as defined in below.
Hematological
Renal
• Calculated or measured glomerular filtration rate (GFR):Any GFR as long as not currently dialysis-dependent
Females of childbearing potential (FCBP)* must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin two acceptable methods of birth control, one highly effective method and one additional effective method at the same time, at least 28 days before she starts taking lenalidomide through 30 days after the last dose of lenalidomide and 5 months after the last dose of isatuximab. FCBP must also agree to ongoing pregnancy testing during the entire duration of treatment and monthly for 5 months after the last dose of isatuximab. Men must agree to use a latex or synthetic condom during sexual contact with a FCBP even if they have had a vasectomy from the time of signing the informed consent form through 30 days after the last dose of lenalidomide and 5 months after the last dose of isatuximab. These same subjects must not donate sperm. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. All subjects enrolled into this trial, must be registered in and must comply with all requirements of the REVLIMID Risk Evaluation and Mitigation Strategy (REMS) program.
Exclusion Criteria
Primary purpose
Allocation
Interventional model
Masking
50 participants in 1 patient group
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Central trial contact
Shamina Williams; Lori Stravers
Data sourced from clinicaltrials.gov
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