Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This study is a single-center, single-arm, open-label, Phase II interventional clinical trial designed to evaluate the efficacy and safety of a CM336 and isatuximab regimen in patients with newly diagnosed multiple myeloma (NDMM) accompanied by renal impairment ([eGFR] < 40 mL/min). Enrolled subjects will receive three consecutive cycles of induction therapy with CM336 in combination with isatuximab.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CM336 plus Isatuximab | Experimental | Enrolled patients will receive 3 cycles of induction therapy with CM336 in combination with isatuximab. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CM336 Plus Isatuximab | Drug | CM336: Administered subcutaneously (SC) via a step-up dosing regimen, which includes a step-up dosing phase and a target dosing phase. Upon reaching the target dose, it will be administered once weekly. Isatuximab: Administered intravenously (IV) at a dose of 10 mg/kg, given weekly during Cycle 1, and every two weeks during Cycles 2 and 3. |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Renal Response Rate (Minor Response or better) | The Overall Renal Response Rate is defined as the percentage of participants who achieve a renal response of Minor Response or better (including Minor Response, Partial Response, and Complete Response) according to the International Myeloma Working Group (IMWG) criteria for renal impairment. | At the end of Cycle 3 (each cycle is 28 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of Renal Partial Response or Better | Rate of renal partial response or better is defined as the percentage of participants who achieve a renal response of Partial Response or better (including Partial Response and Complete Response) according to the International Myeloma Working Group (IMWG) criteria for renal impairment. | At the end of Cycle 3 (each cycle is 28 days) |
Not provided
Inclusion Criteria:
Age 18 to 80 years.
Newly diagnosed symptomatic multiple myeloma (NDMM) according to the International Myeloma Working Group (IMWG) criteria. Patients who have received up to 1 cycle of prior anti-myeloma therapy, excluding immunotherapeutic agents, are allowed to enroll.
Presence of measurable disease at diagnosis, meeting at least one of the following criteria:
A.Serum M-protein ≥ 1 g/dL (> 10 g/L) measured by serum protein electrophoresis (SPEP) (for IgA or IgD myeloma, quantitative IgA or IgD levels may be used instead); OR
B.Urine M-protein ≥ 200 mg/24 hours; OR
C.If both serum and urine M-protein do not meet the above criteria, an abnormal serum free light chain (FLC) ratio (normal FLC ratio: 0.26 to 1.65) with an involved serum FLC level ≥ 100 mg/L.
Accompanied by myeloma-related renal impairment (RI), defined as an estimated glomerular filtration rate (eGFR) < 40 mL/min (calculated using the Modification of Diet in Renal Disease [MDRD] formula). The type of renal impairment must be restricted to cast nephropathy, which can be confirmed by renal biopsy or by the investigator's clinical judgment based on light chain proteinuria. If urine albumin accounts for more than 30% of the total urine protein, a renal biopsy is mandatory to confirm cast nephropathy.
Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2.
Adequate major organ function, meeting the following criteria:
A. Hematological function:
B. Hepatic function:
Alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN), aspartate aminotransferase (AST) ≤ 3 × ULN, and total bilirubin ≤ 2 × ULN (subjects with a history of Gilbert's syndrome are eligible if direct bilirubin ≤ 2.0 × ULN).
C. Coagulation function:
International Normalized Ratio (INR) or Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN.
No active concomitant malignancies or malignancies with an expected survival of less than 12 months.
Willingness to participate in the study, good compliance, and ability to sign the informed consent form (ICF).
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Gang An, PhD & MD | Contact | +86 13502181109 | angang@ihcams.ac.cn |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences | Recruiting | Tianjin | 300000 | China |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| C000599209 | isatuximab |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Hematological Overall Response Rate (ORR) | The percentage of participants who achieve a hematological response of Partial Response (PR) or better (including PR, Very Good Partial Response [VGPR], Complete Response [CR], and Stringent Complete Response [sCR]) according to the International Myeloma Working Group (IMWG) uniform response criteria. | From the first dose of CM336 through 30 days after the last dose of CM336 |
| MRD Negativity Rate | The percentage of participants who achieve MRD negativity in the bone marrow. MRD negativity is defined by a threshold of 10^-5, assessed via Next-Generation Flow (NGF) cytometry in accordance with IMWG criteria. | At the end of Cycle 3 (each cycle is 28 days) |
| Kinetics of Serum Free Light Chain (sFLC) Reduction | The rate and time to achieve a specific percentage or absolute reduction in involved serum free light chain (sFLC) levels from baseline. | From the first dose of CM336 through 30 days after the last dose of CM336 |
| Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Safety will be assessed by monitoring the incidence, nature, and severity of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs), adverse events of special interest (AESIs) such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), graded according to NCI CTCAE v5.0 and ASTCT criteria. Dose interruptions, modifications, or discontinuations due to toxicity will also be recorded. | From the first dose of CM336 through 30 days after the last dose of CM336. |
| PFS | The time from the start of the study treatment to the date of first documented disease progression (according to IMWG criteria) or death from any cause, whichever occurs first. | From the first dose of CM336 up to the date of first documented disease progression or death, up to approximately 24 months. |
| OS | The time from the start of the study treatment to the date of death from any cause. | From the first dose of CM336 up to the date of death from any cause, up to approximately 24 months. |
| D014652 |
| Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |