ELISA in Relapsed/Refractory MM
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorMassachusetts General Hospital
About this trial
This is an open-label phase 2 study of elranatamab in combination with isatuximab administered subcutaneously in patients with relapsed and refractory multiple myeloma (RRMM) who have received at least one prior line of therapy and who have had previous treatment with both immunomodulatory drugs (IMiDs) and a proteasome inhibitor (PI). The subcutaneous injection method of isatuximab administration, including the device used to administer isatuximab, is investigational.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
1. This study will enroll patients with relapsed and refractory multiple myeloma who have had at least 1 prior line of therapy including patients who have had previous treatment with both immunomodulatory drugs (IMiDs) and a proteasome inhibitor (PI). Prior therapy with anti-CD38 and anti-B cell maturation antigen (BCMA) target will be permitted except an anti-BCMA T cell engager.
a. Serum monoclonal protein ≥ 0.5 g/dL. Patients with IgD disease and lower amounts of monoclonal protein may be permitted to enroll with PI approval
b. ≥ 200 mg of monoclonal protein in the urine on 24-hour electrophoresis
c. Serum free light chain ≥ 100 mg/L (10 mg/dL) and abnormal serum free kappa to serum free lambda light chain (FLC) ratio (<0.26 or >1.65)
Disqualifiers
1. Patients with active plasma cell leukemia, POEMS syndrome, or amyloidosis are excluded from this trial.
2. Stem cell transplant within 12 weeks prior to enrollment, or active GVHD.
3. Ongoing Grade ≥2 peripheral sensory or motor neuropathy.
4. History of any grade peripheral sensory or motor neuropathy with prior BCMA directed therapy. History of GBS or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy.
Trial design
Design model
Single group
Treatments tested in this trial
elranatamab
DrugSubcutaneously injected study drug, usually into the abdomen or lower stomach. Each vial of elranatamab contains a sufficient amount of product to ensure an extractable volume of 1.9 mL at a concentration of 40 mg/mL. The dosing is as follows: * Cycle 1 Day 1: 12 mg/0.3 mL; * Cycle 1 Day 4: 32 mg/0.8 mL; * Cycle 1 Day 8, 15, 22: 76 mg/1.9 mL; * Cycles 2-6, Day 1 and 15: 76 mg/1.9 mL; * Cycles 7-12, Day 1: 76 mg/1.9 mL; * Cycles 13-24, Day 1 of Cycles 13, 16, 19, 22 (every 12 weeks): 76 mg/1.9 mL
Isatuximab SC
DrugIsatuximab (SAR650984) is an IgG1 derived monoclonal antibody binding selectively the human CD38 membrane protein. Subcutaneously (SC) injected study drug with each vial containing 140 mg/mL (1400 mg/10mL) isatuximab. Isatuximab SC will be injected using the investigational OBDS and in the following doses: * Cycles 2-6, Day 1 and 15: 1400 mg/10 mL * Cycles 7-12, Day 1: 1400 mg/10 mL * Cycles 13-24, Day 1 of Cycles 13, 16, 19, 22 (every 12 weeks): 1400 mg/10 mL
Isatuximab SC-OBDS
DeviceThe On Body Delivery System (OBDS) also called Isatuximab SC Wearable Injection System, is a sterile, single-use, disposable, elastomeric, user-filled investigational medical device. The OBDD has a reservoir for the drug product (isatuximab). A self-contained, integrated needle (with manual insertion and automatic retraction mechanism) is provided within the OBDS. The OBDS will be used to inject isatuximab each time the participant receives isatuximab in this study. Study drug administration will be done by trained medical professionals in the clinic. The OBDS device will be prepared by the medical professional, placed on the abdomen using the adhesive (sticky) pads that are on the device, the study drug (isatuximab) will be injected, and then the device will be removed.
Treatment groups
30 Participants
are divided into 1 treatment groupGroup A: Elranatamab + Isatuximab-irfcExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
Objective response rate (ORR)
Objective Response will be classified using the International Myeloma Working Group (IMWG) Uniform Response criteria. The rate (ORR) will be calculated using a Simon's two-stage design to test the null hypothesis that the ORR ≤ 0.40 versus the alternative that ORR ≥ 0.60. All patients who receive at least one complete cycle of treatment will be included in a response evaluation. Participants who do not complete cycle 1 (i.e., due to disease progression or who die prior to the end of cycle 1) will not be considered evaluable for response; these participants may be replaced. In the first stage, 22 patients will be accrued. If there are 10 or fewer responses in these 22 patients, the study will be stopped. Otherwise, study will continue to enroll to a total of 30. The null hypothesis will be rejected if 16 or more responses are observed in 30 patients.
Time frame
Day 1 to 2 years post-treatment.Secondary outcomes
1
Incidence of Drug Related Toxicities
All participants who receive at least one dose of study treatment will be evaluable for toxicity. CTCAE v5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) CRS and ICANS grading criteria will be used. Adverse events will be summarized on all patients treated. The number of drug related toxicities, and details (categorization and grading) will be described.
Time frame
Day 1 to 30 days post-treatment (30 days post last dose). Participants can receive treatment until disease progression, unacceptable toxicity, or withdrawal.2
Median Progression Free Survival (PFS)
PFS is defined as the time from start of treatment to disease progression or death from any cause. Patients who have not progressed or died are censored at the date last known progression-free. PFS will be determined according to Kaplan-Meier methodology.
Time frame
Day 1 through end of follow-up, up to 5 years.3
Median Overall Survival (OS)
OS is defined as the time from registration to death due to any cause, or censored at date last known alive. Median OS will be determined according to Kaplan-Meier methodology.
Time frame
Day 1 through end of follow-up, up to 5 years.4
Rate of Minimal Residual Disease (MRD) status in participants who have achieved very good partial response (VGPR) or complete response (CR)
MRD assessment will be assessed by next generation sequencing via bone marrow aspirate whenever a bone marrow sample is obtained. Those with VGPR or CR (per IMWG) will be included in this assessment. The rate is number of MRD-negative compared to MRD-positive and will be reported at various time points (time of VGPR/CR/sCR (variable, 3-6 months on treatment) and after 12 and 24 months on treatment).
Time frame
Screening through 24 months on treatment.Sponsors and contacts
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Source ClinicalTrials.gov