The goal of this clinical trial is to learn whether CM336, a BCMA/CD3 bispecific antibody, can improve treatment outcomes when combined with isatuximab, lenalidomide, and bortezomib in adults with newly diagnosed primary plasma cell leukemia (pPCL). The study will also evaluate the safety of this treatment combination.
The main questions it aims to answer are:
How many participants achieve minimal residual disease (MRD) negativity after 9 treatment cycles? What side effects occur during treatment with CM336 combined with isatuximab, lenalidomide, and bortezomib? How many participants respond to treatment, and how long do those responses last? How long do participants remain free from disease progression, and how long do they survive after starting treatment? All participants will receive the study treatment. There is no comparison group in this study.
Participants will:
Receive CM336 by subcutaneous injection together with isatuximab, lenalidomide, and bortezomib in 28-day treatment cycles.
Undergo regular blood tests, bone marrow examinations, and disease assessments to monitor treatment response and safety.
Have stem cells collected after the first 3 treatment cycles if appropriate. Continue treatment for up to 18 cycles, followed by maintenance treatment with isatuximab and lenalidomide until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision.
Be monitored throughout the study for side effects.
Able to understand and voluntarily sign a written informed consent form (ICF).
Age 18 to 75 years.
≥5% circulating plasma cells on peripheral blood smear; or
Absolute circulating plasma cell count >2 × 10⁹/L.
Diagnosis of smoldering multiple myeloma (SMM), monoclonal gammopathy of undetermined significance (MGUS), Waldenström macroglobulinemia, POEMS syndrome, amyloidosis, or secondary plasma cell leukemia.
Central nervous system (CNS) involvement or clinical evidence of leptomeningeal involvement.
Known intolerance, hypersensitivity, allergy, or contraindication to CM336, isatuximab, bortezomib or lenalidomide.
Concurrent active malignancy or any serious concomitant disease that, in the investigator's judgment, could compromise participant safety or interfere with study participation.