CM336 Plus Isa-VR in Newly Diagnosed Primary Plasma Cell Leukemia (CAREMM-011)

A Prospective, Single-Arm, Single-Center, Phase II Study Evaluating the Safety and Efficacy of CM336 in Combination With Isatuximab, Lenalidomide, and Bortezomib in Newly Diagnosed Primary Plasma Cell Leukemia

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Plasma Cell Leukemia (PCL)
• Intervention / Treatment: Drug: CM336; Drug: Isatuximab; Drug: Bortezomib; Drug: Lenalidomide

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gang An, PhD & MD; Phone Number: +86 13502181109; Email: angang@ihcams.ac.cn

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300000
      • Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
      • Contact: Gang An, PhD & MD; Phone Number: +0086 13502181109; Email: angang@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Able to understand and voluntarily sign a written informed consent form (ICF).
2. Age 18 to 75 years.

3. Newly diagnosed primary plasma cell leukemia (pPCL) according to International Myeloma Working Group (IMWG) criteria, defined as either:

   • ≥5% circulating plasma cells on peripheral blood smear; or
   • Absolute circulating plasma cell count >2 × 10⁹/L.

   Patients who have received no more than one prior cycle of anti-myeloma therapy before enrollment are eligible, provided they have not received monoclonal antibodies or immunotherapy agents.

4. Measurable disease, defined by at least one of the following:

   • Serum M-protein ≥10 g/L as measured by serum protein electrophoresis (SPEP); for IgA or IgD myeloma, quantitative IgA or IgD levels may be used instead;
   • Urine M-protein ≥200 mg/24 hours;
   • If neither serum nor urine M-protein meets the above criteria, involved serum free light chain (FLC) ≥100 mg/L with an abnormal serum FLC ratio (normal range: 0.26-1.65).

5. Adequate hepatic function, defined as:

   • Total bilirubin <1.5 × upper limit of normal (ULN), except for participants with Gilbert syndrome, who must have total bilirubin <3 × ULN;
   • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN.
6. Adequate renal function, defined as creatinine clearance ≥30 mL/min, calculated using the Cockcroft-Gault formula.

7. Adequate hematologic function within 7 days prior to enrollment, defined as:

   • White blood cell (WBC) count ≥1.5 × 10⁹/L;
   • Absolute neutrophil count (ANC) ≥1.0 × 10⁹/L;
   • Hemoglobin ≥70 g/L;
   • Platelet count ≥50 × 10⁹/L;

   Alternatively, eligibility may be determined by the investigator based on clinical judgment.

8. Participants receiving hematopoietic growth factor support, including erythropoietin, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), or thrombopoietic agents, must have a washout period of at least 2 weeks between the last administration of growth factor support and screening assessments.

9. Participants receiving blood product transfusions must meet the following requirements:

   • At least 2 weeks between the last red blood cell (RBC) transfusion and hemoglobin assessment at screening;
   • At least 1 week between the last platelet transfusion and platelet count assessment at screening.
10. Able and willing to receive protocol-recommended prophylactic anticoagulation therapy.
11. Female participants of childbearing potential must have a negative serum pregnancy test at screening and agree to use effective contraception from the time of signing the informed consent form, throughout study treatment, and for at least 3 months after the last dose of study treatment.

Male participants, including those who have undergone vasectomy, must agree to use condoms during sexual intercourse with women of childbearing potential and must not plan to father a child from the time of signing informed consent through 3 months after the last dose of study treatment.

Exclusion Criteria:

1. Diagnosis of smoldering multiple myeloma (SMM), monoclonal gammopathy of undetermined significance (MGUS), Waldenström macroglobulinemia, POEMS syndrome, amyloidosis, or secondary plasma cell leukemia.
2. Central nervous system (CNS) involvement or clinical evidence of leptomeningeal involvement.
3. Known intolerance, hypersensitivity, allergy, or contraindication to CM336, isatuximab, bortezomib or lenalidomide.

4. Severe and/or uncontrolled cardiovascular disease, including:

   Unstable angina; Symptomatic congestive heart failure; Myocardial infarction within 6 months prior to enrollment; Severe and uncontrolled cardiac arrhythmias; Any other cardiovascular or cerebrovascular condition deemed by the investigator to make participation inappropriate.

5. Active infection, including:

   Human immunodeficiency virus (HIV) infection; Active hepatitis B infection (HBV DNA positive); Active hepatitis C infection (HCV RNA positive); Active or latent syphilis infection (positive Treponema pallidum antibody test); Active pulmonary tuberculosis, as evidenced by chest imaging or other relevant assessments within 3 months prior to screening or during the screening period; Any other infection considered by the investigator to make participation inappropriate.

6. Concurrent active malignancy or any serious concomitant disease that, in the investigator's judgment, could compromise participant safety or interfere with study participation.
7. Pregnant or breastfeeding women.
8. Estimated life expectancy of less than 6 months.
9. Active gastrointestinal disorders that may impair the participant's ability to swallow oral medication or may interfere with the absorption of study treatment.
10. Major surgery within 2 weeks prior to enrollment (e.g., surgery requiring general anesthesia), incomplete recovery from prior surgery, or planned major surgery during study participation. Kyphoplasty and vertebroplasty are not considered major surgery. Participants undergoing procedures under local anesthesia may be eligible.
11. Receipt of a live attenuated vaccine within 4 weeks before the first dose of study treatment.
12. Any active severe psychiatric disorder, medical condition, symptom, or other circumstance that, in the investigator's judgment, may interfere with treatment, protocol compliance, or the ability to provide informed consent.
13. Inability or unwillingness to provide written informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CM336 plus Isa-VR; Enrolled patients will receive 18 cycles of therapy with CM336 in combination with isatuximab, bortezomib and lenalidomide

Drug: CM336; CM336 is administered subcutaneously (SC) using a step-up dosing regimen, followed by a target dose of 160 mg. During Cycle 1, CM336 is administered weekly; from Cycle 2 through Cycle 18, it is administered every 4 weeks.; Drug: Isatuximab; Isatuximab is administered intravenously (IV) at 10 mg/kg. It is given weekly during Cycle 1, every 2 weeks during Cycles 2-12, and every 4 weeks during Cycles 13-18.; Drug: Bortezomib; Bortezomib is administered subcutaneously (SC) at 1.3 mg/m² once weekly during Cycles 1-18.; Drug: Lenalidomide; Lenalidomide is administered orally at 25 mg once daily on Days 1-21 of each 28-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Minimal residual disease (MRD) negative rate	After 9 cycles (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence and severity of adverse events (AEs)	From the first dose of CM336 through 30 days after the last dose of CM336, up to approximately 18 months.
Duration of MRD negativity	From the date of first documented MRD negativity until disease progression, death, or end of follow-up, whichever occurs first, assessed up to approximately 36 months.
Hematological Overall Response Rate (ORR)	Up to 18 treatment cycles, each cycle is 28 days
Progression-free survival (PFS)	From the first dose of study treatment until the date of first documented disease progression or death from any cause, whichever occurs first, assessed up to approximately 36 months.
Overall survival (OS)	From the first dose of study treatment until death from any cause, assessed up to approximately 36 months.

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Estimated): June 20, 2026
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): December 30, 2031

Study Registration Dates

• First Submitted: June 8, 2026
• First Submitted That Met QC Criteria: June 11, 2026
• First Posted (Actual): June 17, 2026

Study Record Updates

• Last Update Posted (Actual): June 17, 2026
• Last Update Submitted That Met QC Criteria: June 11, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: BCMA/CD3 bispecific antibody; CM336; Primary plasma cell leukemia
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Leukemia; Multiple Myeloma; Hemic and Lymphatic Diseases; Leukemia, Plasma Cell; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Piperidines; Inorganic Chemicals; Boronic Acids; Acids, Noncarboxylic; Acids; Boron Compounds; Pyrazines; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; Bortezomib; isatuximab
• Other Study ID Numbers: IIT2026071

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No