Relapsed/Refractory Multiple Myeloma
Conditions
Brief summary
This is a Phase I/II, single-arm, open-label, multicenter clinical trial in patients with relapsed/refractory multiple myeloma (R/R MM). The study aims to evaluate the safety, tolerability, efficacy, cellular kinetics, and immunogenicity of CT0596.
Detailed description
Phase I employs a BOIN design for dose escalation to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D). Phase II will further confirm the clinical efficacy of CT0596 at the RP2D in R/R MM, with the primary efficacy endpoint being the overall response rate (ORR) at Week 12 post-infusion, assessed by an Independent Review Committee (IRC) per International Myeloma Working Group(IMWG) 2016 criteria.
Interventions
DRUGCT0596
CAR-T cells
Sponsors
UCARsgen Biotech Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Voluntarily participate in the trial; fully understand and sign the informed consent form (ICF); willing and able to comply with all trial procedures. * Age ≥ 18 years, male or female. * Patients with relapsed/refractory multiple myeloma (R/R MM) who have received at least 3 prior lines of therapy, including at least one proteasome inhibitor (PI), at least one immunomodulatory agent (IMiD), and at least one anti-CD38 monoclonal antibody. * Relapsed/refractory disease defined per IMWG 2016 response criteria,. * Must have measurable disease: * Life expectancy ≥ 12 weeks. * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. * Must have Adequate organ function * Female participants of childbearing potential must have a negative pregnancy test at screening and prior to lymphodepletion, and must agree to use highly effective contraception for at least 1 year after CT0596 infusion, and absolutely refrain from oocyte donation. Male participants with active sexual life with WOCBP must agree to use highly effective contraception for at least 1 year after infusion and absolutely refrain from sperm donation。
Exclusion criteria
* Pregnant or lactating women. * Positive for HIV, syphilis, active hepatitis B (HBV-DNA above LLoD), or active hepatitis C (positive for both HCV antibody and HCV-RNA). * Presence of any uncontrolled active infection, including but not limited to active tuberculosis (per investigator), active CMV and/or EBV infection, etc. * Toxicity from prior therapy not recovered to ≤ Grade 1 per Common Terminology Criteria for Adverse Events(CTCAE) V5.0 (except alopecia and other events deemed tolerable by the investigator). * Prior BCMA-targeted therapy (refer to the protocol for exceptions). * Prior allogeneic stem cell transplantation; or autologous SCT within 3 months prior to signing ICF; or planned Hematopoietic Stem Cell Transplantation(HSCT) during the trial. * Received disease-directed therapy within 14 days or 5 half-lives (whichever is shorter) prior to lymphodepletion. * Received any cell therapy within 6 months prior to ICF; or prior CAR-T with best response \< PR. * Received systemic corticosteroids equivalent to \> 15 mg/day of prednisone within 7 days prior to lymphodepletion (excluding topical use). * Received live-attenuated, inactivated, or RNA vaccines within 4 weeks prior to lymphodepletion. * Major surgery within 2 weeks prior to lymphodepletion, or planned major surgery during trial or within 4 weeks after treatment (excluding local anesthesia surgeries). * Allergy or intolerance to lymphodepletion agents, tocilizumab, or any component of infusion (e.g., DMSO); or history of severe allergy such as anaphylactic shock. * Diagnosed with secondary plasma cell leukemia, solitary extramedullary plasmacytoma, Waldenström macroglobulinemia, POEMS syndrome, or primary light chain amyloidosis at screening. * Severe cardiac diseases within 6 months prior to screening. * Severe pulmonary disease that may jeopardize the patient's life per investigator. * Inability to tolerate an adequate lymphodepletion regimen. * Secondary primary malignancy requiring treatment or not in complete remission within 2 years prior to screening, except for successfully treated non-metastatic basal/squamous cell skin carcinoma, non-metastatic prostate cancer, carcinoma in situ (breast/cervix), non-muscle-invasive bladder cancer, or low-grade thyroid cancer. * Known symptomatic central nervous system (CNS) disease or suspected CNS metastasis. * Patients assessed by the investigator as unable or unwilling to comply with protocol requirements, or otherwise unsuitable for participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I:Adverse Events (AE) after CT0596 infusion | 24months after CT0596 infusion | An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria. |
| Phase I:Maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) | 28 days after CT0596 infusion | Evaluate Dose limited toxicity and recommended dosage range after CT0596 infusion. |
| Phase II:Overall response rate (ORR) | Week 12 after CT0596 infusion | Overall response rate (ORR) at Week 12 post-infusion, assessed by an Independent Review Committee (IRC) per IMWG 2016 criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) as assessed by IRC and investigator | 24 months after CT0596 infusion | Overall response rate (ORR) defined as proportion of patients achieving partial response or better based on International Myeloma Working Group defined response criteria by IRC and investigator. |
| Complete response/stringent complete response (CR/sCR) rate | 24 months after CT0596 infusion | Rate of complete response/stringent complete response (CR/sCR) defined as proportion of patients achieving CR or better based on IMWG defined response criteria. |
| Rate of very good partial response (VGPR) and above | 24 months after CT0596 infusion | the proportion of patients achieving very good partial response, complete response or stringent complete response per IMWG response criteria. |
| Duration of response (DOR) | 24 months after CT0596 infusion | DOR is defined as the time from first achieving Partial Response (PR) or better to confirmed disease progression or death from any cause. |
| Minimal residual disease (MRD) negative rate | 24 months after CT0596 infusion | MRD negative rate is defined as the proportion of patients achieve a MRD negative by NGF(Next Generation Flow) at a sensitivity of 10-5. |
| Time to response (TTR) | 24 months after CT0596 infusion | TTR defined as the time from the date of infusion to the date of initial assessment of PR or better according to IMWG2016 criteria. |
| Progression-free survival (PFS) | 24 months after CT0596 infusion | PFS defined as the time from the date of infusion of the subject to the first assessment of confirmed disease progression or death from any cause according to IMWG2016 criteria, whichever occurs first. |
| Overall survival (OS) | after CT0596 infusion | OS defined as the time from the date of infusion of the subject to death from any cause. |
| Pharmacokinetic parameters of CT0596, including CAR copy number, peak value, AUC (area under the curve), in vivo persistence, etc | 24 months after CT0596 infusion | Time to peak expansion, peak expansion, area under the curve (AUC) and duration in plasma after infusion of CT0596 cells. |
| Cytokines in the peripheral blood | up to 24 months after CT0596 infusion | Serum concentrations of interleukin (IL)-6 after CT0596 infusion. |
| Immunogenicity (anti-drug antibodies) | up to 24 months after CT0596 infusion | Serum concentrations of anti-drug antibodies after CT0596 infusion |
Countries
China
Contacts
CONTACTJuan Du
CONTACTChengcheng Fu
Outcome results
None listed