Exploratory Clinical Trial of the Safety and Efficacy of CT071 Injection in Patients With High Risk Newly Diagnosed Multiple Myeloma

Shanghai Changzheng Hospital1 site in 1 country10 target enrollmentJune 6, 2024

ConditionsMultiple Myeloma

InterventionsChimeric antigen receptor modified T cells Infusion

DrugsChimeric antigen receptor modified T cells Infusion

Overview

Phase: Early Phase 1
Intervention: Chimeric antigen receptor modified T cells Infusion
Conditions: Multiple Myeloma
Sponsor: Shanghai Changzheng Hospital
Enrollment: 10
Locations: 1
Primary Endpoint: Adverse Events (AE) after CT071 infusion
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials Related News

Overview

Brief Summary

This trial is a single-arm, single-center, open-label clinical trial to evaluate the safety, efficacy, and metabolism kinetics of CT071 in patients with high-risk newly diagnosed multiple myeloma.

Detailed Description

This trial is a single-arm, single-center, open-label clinical trial to evaluate the safety, efficacy, and metabolism kinetics of CT071 in patients with high-risk newly diagnosed multiple myeloma (HRNDMM).

Registry

clinicaltrials.gov

Start Date

June 6, 2024

End Date

June 3, 2027

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Shanghai Changzheng Hospital

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Participants must meet all of the following criteria to be enrolled:
•1.Volunteer to participate in the clinical trial; the participants themselves fully understand and are informed of this study, and sign the informed consent form and are willing to follow and able to complete all trial procedures;
•2.Age ≥ 18 years, male or female;
•3.Participants must have newly diagnosed with multiple myeloma according to International Myeloma Working Group diagnostic criteria 2014 ;
•4.Measurable disease based on at least one of the following parameters (International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma 2016); the values for these parameters obtained up to 60 days prior to signing the Informed Consent Form including the results at the time of diagnosis may be used.
•Serum M-protein ≥ 1.0 g/dL;
•Urine M-protein ≥ 200 mg/24 hr;
•Serum free light chain (FLC): involved FLC level ≥ 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal.
•5.Known to have the following high risk factors, i.e. At least one of the following conditions is met:
•Meet any one or more of the cytogenetic criteria: del (17p); t (4; 14); t (14; 16); t (14; 20); 1q21 amplification ≥ 4 copies; 2)R-ISS stage 3; R2-ISS stages 3 and 4; 3)Presence of soft tissue extramedullary plasmacytoma 4)2%-5% in peripheral plasma cells;

Exclusion Criteria

•Participants were not enrolled in the trial if they met any of the following criteria:
•Patients with non-secretory MM.
•Prior treatment for MM other than up to 2 cycles of (bortezomib, lenalidomide, dexamethasone) for induction, including but not limited to cytotoxic therapy, proteasome inhibitors, immunomodulators, targeted therapy, radiotherapy (patients are eligible for this trial if the radiation field covers ≤ 5% bone marrow reserve regardless of the end date of radiotherapy), epigenetic therapy, etc.
•Pregnant or lactating females.
•Patients with severe mental disorders or altered mental status, history of central nervous system disease, such as epilepsy, intracranial hemorrhage, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, memory impairment, spinal cord compression, psychiatric disease or any disease involving the central nervous system, or suspected central nervous system (CNS) metastasis, or any autoimmune disease involving the CNS, with or suspected CNS infiltration.
•Participants had other malignancies, including the following that were considered to have been successfully treated: non-metastatic basal cell or squamous cell skin cancer, non-metastatic prostate cancer, carcinoma in situ of the breast or cervix, and non-muscle invasive bladder cancer.
•Active autoimmune disease that results in end organ damage or requires systemic immunosuppressive/systemic disease modifying drugs, including but not limited to Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus and other patients requiring long-term immunosuppressive therapy.
•Have any uncontrolled active infection (defined as exhibiting persistent signs or symptoms associated with infection that do not improve despite appropriate anti-infective therapy), or other serious active viral, bacterial, or uncontrolled systemic fungal infection. I
•Positive test results for biomarkers of any of the following pathogenic microorganisms: human immunodeficiency virus (HIV) antibody, Treponema pallidum antibody (TPPA), hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) (core antigen \[HBcAb\] positive must have DNA copies below the lower limit of normal).
•Vaccination with live attenuated vaccine or mRNA vaccine within 8 weeks and inactivated vaccine within 4 weeks prior to screening.

Arms & Interventions

Chimeric antigen receptor modified T cells Infusion

Chimeric antigen receptor modified T cells chimeric antigen receptor T cells

Intervention: Chimeric antigen receptor modified T cells Infusion

Outcomes

Primary Outcomes

Adverse Events (AE) after CT071 infusion

Time Frame: From first dose of study drug administration to end of treatment (up to 24 months)

An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), with the exception of cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS).

Recommended Phase II Dose of CT071 in patients with high-risk newly diagnosed multiple myeloma

Time Frame: Assessed from the date of first dose of study treatment until 28 days

Evaluate Dose limited toxicity and adverse events after CT071 infusion

Overall response rate (ORR)

Time Frame: From first dose of study drug administration to end of treatment (up to 24 months)

ORR defined as proportion of patients achieving partial response or better based on International Myeloma Working Group defined response criteria

Secondary Outcomes

Peak Plasma Concentration (Cmax) of CAR T cells(From first dose of study drug administration to end of treatment (up to 24 months))
Presence of anti-CT071 antibodies(From first dose of study drug administration to end of treatment (up to 24 months))
Minimal residual disease (MRD) negative rate(From first dose of study drug administration to end of treatment (up to 24 months))
Markers(From first dose of study drug administration to end of treatment (up to 24 months))
Immune-related proteins after CT071 infusion(From first dose of study drug administration to end of treatment (up to 24 months))
Complete response/stringent complete response (CR/sCR) rate(From first dose of study drug administration to end of treatment (up to 24 months))
Progression-free survival (PFS)(From first dose of study drug administration to end of treatment (up to 24 months))
Time to best response (TTBR) as assessed by the investigator(From first dose of study drug administration to end of treatment (up to 24 months))
Overall survival (OS)(From first dose of study drug administration to end of treatment (up to 24 months))
Duration of MRD negativity(From first dose of study drug administration to end of treatment (up to 24 months))
Cytokines in the peripheral blood after CT071 infusion(From first dose of study drug administration to end of treatment (up to 24 months))
Duration of response (DOR)(From first dose of study drug administration to end of treatment (up to 24 months))
Time to response (TTR)(From first dose of study drug administration to end of treatment (up to 24 months))
Area under the plasma concentration versus time curve (AUC) of CART cells(From first dose of study drug administration to end of treatment (up to 24 months))
Level of CAR-T Cell Expansion persistence(From first dose of study drug administration to end of treatment (up to 24 months))