- Histologically confirmed diagnosis of multiple myeloma with a measurable disease
parameter at time of screening. A measurable disease parameter is defined as one or
more of the following:
- Serum monoclonal protein ≥ 0.5 g/dL
- 24 hour urine monoclonal protein ≥ 0.2 g/24 hour
- Serum free light chain ratio > 5x normal ratio with an absolute difference of
10mg/dL between the involved and uninvolved free light chain
- Soft tissue plasmacytoma ≥ 2 cm measurable by either physical examination and/or
applicable radiographs (e.g. MRI, CT, etc.)
- Bone marrow plasma cells ≥ 30%
- Penta-refractory disease defined as both of the following:
- Previously received treatment with an alkylating agent, bortezomib, carfilzomib,
lenalidomide, pomalidomide, and daratumumab, in combination or as single-agents.
- Refractory (defined per IMWG Consensus Criteria as disease that is nonresponsive
while on therapy, or progresses within 60 days of last dose) to a proteasome
inhibitor, an IMID, and their most recent therapy.
- Patients must have had at least 3 cycles of daratumumab treatment with at least 6
weeks from the last treatment with daratumumab to the first study treatment OR at
least 2 cycles of daratumumab treatment in case another therapy is given between
daratumumab and isatuximab with at least 12 weeks from the last treatment with
daratumumab to the first study treatment.
- At least 18 years of age.
- Performance status of ECOG ≤ 2 Note: Participants with lower performance status based
solely on bone pain secondary to multiple myeloma will be eligible.
- Normal bone marrow and organ function as defined as ALL of the following:
- Absolute neutrophil count ≥ 1500/mm3
- Platelets ≥ 75,000 (transfusions not permitted within 7 days of screening)
- ALT (SGPT) and AST (SGOT) < 3.5 x the upper limit of the institutional normal
- Total bilirubin ≤ 2.0 x mg/dL.
- Creatinine clearance > 30 ml/min using Cockcroft-Gault formula
- Females of childbearing potential (FCBP) must agree to refrain from becoming pregnant
while on study drug and for 3 months after discontinuation from study drug, and must
agree to use adequate contraception including hormonal contraception, (e.g. birth
control pills, etc.), barrier method contraception (e.g. condoms), or abstinence
during that time frame. Men engaging in sexual intercourse with a FCBP must agree to
use adequate contraception including hormonal contraception, (e.g. birth control
pills, etc), barrier method contraception (e.g. condoms), or abstinence while on study
drug and for 3 months after discontinuation from study drug
- Ability to understand and willing to sign a written informed consent document.
- Prior exposure to isatuximab or bendamustine
- History of plasma cell leukemia or MM CNS involvement.
- Receiving renal replacement therapy, hemodialysis, or peritoneal dialysis.
- Diagnosed with another concurrent malignancy requiring treatment.
- Known active hepatitis A, B, or C. Antibody testing not required for screening.
- Known intolerance to infused protein products, sucrose, histidine, polysorbate 80 or
known hypersensitivity to any of the components of study therapy.
- Receiving any other investigational agents within 14 days prior to enrollment.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
pregnancy test within 14 days of study entry.
- Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or
they have a history of AIDS-defining opportunistic infection within the 12 months
prior to registration. Concurrent treatment with effective ART according to DHHS
treatment guidelines is recommended.