Relapsed/Refractory B-Cell Neoplasms
Conditions
Brief summary
A Clinical Study to Explore the Safety, Efficacy and Cellular Metabolic Kinetics of CT1194D CAR-T Cells Injection in Patients with Relapsed/Refractory B-Cell Neoplasms
Detailed description
This is a single-arm, open-label, dose exploratory clinical study to evaluate the safety, efficacy, cellular Metabolic Kinetics of CT1194D CAR-T Cells in patients with relapsed/refractory B-cell Non-Hodgkin's Lymphoma (R/R B-NHL) and relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). It is planned to enroll around 20-30 participants.
Interventions
CT1194D cells infusion
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* R/R B-NHL Inclusion Criteria： 1\. Voluntary participation in the clinical study; I fully understand and are informed of this study and sign the informed consent form; Willing to follow and able to complete all study procedures; 2. Age 18-75 years (inclusive) 3. Histologically or cytologically confirmed diagnosis of R/R B-NHL according to the WHO classification of lymphoid hyperplasia and neoplasms, 5th Edition 2022, including: 1\) Cohort A1: large B-cell lymphoma, including diffuse large B-cell lymphoma unspecified (DLBCL, NOS), primary mediastinal large B-cell lymphoma (PMBCL), high-grade B-cell lymphoma, large B-cell lymphoma transformed from follicular lymphoma (FLBL)/Grade 3b FL; 2) Cohort A2: Mantle cell lymphoma (MCL); 3) Cohort B: follicular lymphoma grade 1-3a; 4. Prior Therapy Requirements: 1. Cohort A1: Patients who have previously received standard systemic therapy, including regimens containing anti-CD20 drugs (except CD20 negative) and anthracyclines; 2. Cohort A2: Prior standard systemic therapy, including an anti-CD20 agent (except CD20 negative), an anthracycline-containing regimen, or a BTK inhibitor; 3. Cohort B: previously received standard systemic therapy, including regimens containing anti-CD20 drugs (except CD20 negative) and anthracyclines; 5. Intolerance during the last treatment, or the need for new treatment after the last adequate treatment (at least 2 cycles) or as assessed by the investigator; 6. At least one of the following: 1\) As measured by CT: Nodal lesions \> 1.5 cm in long diameter or extranodal lesions \> 1.0 cm in long diameter and measurable in short axis; 2) As measured by PET: FDG uptake fraction of 4 or 5; 8. Eastern Cooperative Oncology Group (ECOG) score 0-1; 9. Participants should meet the following test results (there should be no ongoing supportive care): 1. Hematology: ① Platelet (PLT) ≥ 75 × 109/L (study participants with bone marrow or peripheral blood involvement: PLT ≥ 50 × 109/L), ② Hemoglobin (Hb) ≥ 80 g/L (study participants with bone marrow or peripheral blood involvement: Hb ≥ 60 g/L); 2. Endogenous creatinine clearance ≥ 50 mL/min, or creatinine ≤ 1.5 × ULN (using Cockcroft-Gault formula); 3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN, total bilirubin ≤ 1.5 × ULN; If lymphoma invades the liver: AST and ALT ≤ 5 × ULN, total bilirubin ≤ 3.0 × ULN; 4. International normalized ratio (INR) and activated partial thromboplastin time (APTT) were required to be ≤ 1.5 × ULN. 5. Oxygen saturation ≥ 92% in non-oxygen inhalation state; 6. Left ventricular ejection fraction (LVEF) ≥ 50% (LVEF value near the cut-off value can be enrolled after adequate risk assessment by the investigator); 10. Female participants of child-bearing potential must have a negative pregnancy test at the time of screening and before receiving lymphodepletion therapy, be willing to use a highly effective and reliable method of contraception within 1 year after receiving study treatment, and absolutely prohibit egg donation within 1 year after receiving study treatment infusion during the study; A male participant, if sexually active with a female of childbearing potential, is willing to use a highly effective and reliable method of contraception for 1 year after receiving study treatment. All male participants absolutely refrain from donating sperm for 1 year after receiving study treatment infusion during the study. * R/R B-ALL Inclusion Criteria： 1. Voluntary participation in the clinical study; I fully understand and are informed of this study and sign the informed consent form; Willing to follow and able to complete all study procedures; 2. Age 18-75 years (inclusive); 3. Morphologically, immunologically, or molecularly confirmed diagnosis of R/R B-ALL (Cohort C) and 1 of the following criteria is met: <!-- --> 1. Patients who did not achieve complete remission after standard induction regimen chemotherapy or had early relapse after complete remission (\< 12 months) or late relapse after complete remission (≥ 12 months) and did not achieve complete remission after standard one course of induction regimen chemotherapy and relapsed after 2 or more CR or CRi; 2. For Ph + ALL patients who have not achieved complete remission after receiving at least one TKI treatment in addition to standard induction chemotherapy, or relapsed after complete remission (those who cannot tolerate TKI treatment or have contraindications for TKI treatment, or have T315I mutation are not required to receive TKI treatment); 4. Leukemia cells with positive expression of CD19 and/or CD20 in bone marrow or peripheral blood; 5. Bone marrow cell morphology or peripheral blood indicates blast ratio ≥ 5%; 6. Estimated survival \> 12 weeks; 7. Eastern Cooperative Oncology Group (ECOG) score 0-2; 8. Participants should meet the following test results (there should be no ongoing supportive care): <!-- --> 1. Endogenous creatinine clearance ≥ 50 mL/min, or creatinine ≤ 1.5 × ULN (using the Cockcroft-Gault formula); 2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN, total bilirubin ≤ 1.5 × ULN; If hepatobiliary involvement: AST and ALT ≤ 5 × ULN, total bilirubin ≤ 3.0 × ULN; 3. International normalized ratio (INR) and activated partial thromboplastin time (APTT) must be ≤ 1.5 × ULN; 4. Oxygen saturation ≥ 92% in non-oxygen inhalation state; 5. Left ventricular ejection fraction (LVEF) ≥ 50% (LVEF values near the cut-off value may be enrolled after adequate risk assessment by the investigator). 9\. Female participants of child-bearing potential must have a negative pregnancy test at the time of screening and before receiving lymphodepletion therapy, be willing to use a highly effective and reliable method of contraception for 1 year after receiving study treatment, and absolutely refrain from egg donation for 1 year after receiving study treatment infusion during the study; A male participant, if sexually active with a female of childbearing potential, is willing to use a highly effective and reliable method of contraception for 1 year after receiving study treatment. All male participants absolutely refrain from donating sperm for 1 year after receiving study treatment infusion during the study.
Exclusion criteria
* R/R B-NHL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To assess the severity and incidence of DLTs, treatment-related adverse events (TRAE), and adverse events of special interest (AESI) after CT1194D infusion | 12 months after CT1194D infusion | — |
| MTD or dose range | Up to 28 days after CAR-T cells infusion | To explore the maximum tolerated dose (MTD) or dose range of CT1194D |
Secondary
| Measure | Time frame |
|---|---|
| Overall Response Rate (ORR) | Evaluate at 4, 8, 12 weeks and 6,9,12month after CAR-T infusion |
| Complete response rate (CRR) | 12 months after CT1194D infusion |
| Minimal Residual Disease Negative (MRD-) Proportion (R/R B-ALL) | 12 months after CT1194D infusion |
| Duration of response (DOR) | 12 months after CT1194D infusion |
| Time to response (TTR) | 12 months after CT1194D infusion |
| Time to complete response (TTCR) | 12 months after CT1194D infusion |
| Progression-free survival (PFS) | 12 months after CT1194D infusion |
| Overall Survival (OS) | 12 months after CT1194D infusion |
Countries
China
Contacts
Primary ContactLiang Huang
Outcome results
None listed