The Application of CAR-T Cell Therapy in Relapsed and Refractory Malignant Hematologic Tumors

NCT06911710 | Recruiting Phase 1

• 1 other identifier: IRB2022-YX-013-01
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an open, single-arm, prospective, Phase I/II clinical study using "3+3" dose escalation and dose expansion to investigate the safety, maximum tolerated dose, in vivo pharmacokinetic profile, and preliminary efficacy of CAR-T cell injections for the treatment of relapsed/refractory malignant hematological neoplasms in subjects.

Conditions

Lymphoma, B-cell, Aggressive Non-Hodgkin (B-NHL); AML (Acute Myelogenous Leukemia); Myeloma Multiple; B-ALL; T-ALL/Lymphoma; T-lymphocyte Lymphoma

Outcome Measures

Primary Outcomes (1)

• The incidence of adverse events

  Day 28

Secondary Outcomes (5)

• Objective response rate (ORR)

  At 3, 6, 9, 12, 18, and 24 months post-treatment follow up

• Complete response rate (CRR)

  At 3, 6, 9, 12, 18, and 24 months post-treatment follow up

• Duration of response (DOR)

  At 3, 6, 9, 12, 18, and 24 months post-treatment follow up

• Progression free survival (PFS)

  At 3, 6, 9, 12, 18, and 24 months post-treatment follow up

• Overall survival (OS)

  At 3, 6, 9, 12, 18, and 24 months post-treatment follow up

Other Outcomes (1)

• Kinetics of CAR-T cells

  At 3, 6, 9, 12, 18, and 24 months post-treatment follow up

Study Arms (1)

CAR-T treatment group

EXPERIMENTAL

CAR-T Cells infusion（CAR 2219，CAR2019，CAR19 ect）

Drug: CAR-T Cells infusion（CAR2219,CAR2019, CAR19 etc）

Interventions

CAR-T Cells infusion（CAR2219,CAR2019, CAR19 etc） DRUG

Phase I study: dose-escalation component.This part follows the "3+3" dose-escalation model, with 5 dose groups: 1×10\^6, 1.5×10\^6, 2×10\^6, 2.5×10\^6, 3×10\^6 CAR+ cells/kg (different target CAR-T can be adjusted by the investigator according to the dose used in the previous clinical trial). Each dose group enrolled 3\~6 patients with relapsed/refractory hematological diseases respectively, totaling 15\~30 subjects, in order to evaluate the safety of CAR-T cells for the treatment of relapsed/refractory malignant hematological neoplasms and to determine the MTD. Phase II study: dose-expansion portion. After the MTD was confirmed, in the dose-expansion portion of the study (Phase II), it was expected that 65\~60 subjects would receive the CAR-T cell injection infusion under RP2D to further evaluate the efficacy of CAR-T cell injection.

CAR-T treatment group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• With their own consent and have signed an informed consent form, willing and able to comply with the planned visits, study treatment, laboratory tests and other experimental procedures; Patients with recurrent/refractory malignant hematologic tumors as determined by clinical diagnosis; Age 18 years and above, both male and female; Subjects with a physical status of 0\~2 on the Eastern Cooperative Oncology Group (ECOG) score; Expected survival \>3 months from the date of informed consent; HGB ≥ 60g/L (transfusion is allowed); Liver and kidney function, cardiopulmonary function meet the following requirements: a) creatinine ≤1.5×ULN;b) Left ventricular ejection fraction ≥50%; c) Blood oxygen saturation \>90%;d) Total bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 2.5 × ULN; Subjects with pregnancy plans must agree to use contraception prior to enrollment in the study and after the study has lasted for six months; subjects should notify the investigator immediately if they become pregnant or suspect pregnancy.
• Subjects in the different cohorts will still be required to fulfill the following conditions:
• Lymphoma Cohort:
• B-cell lymphoma Diagnosis of CD19+ and/or CD20+ and/or CD22+ and/or BAFF+ B-cell lymphoma confirmed by pathology and histology; Inert B-cell lymphoma (CLL, FL, MZL, LPL, HCL); Aggressive B-cell lymphoma (DLBCL, BL, MCL).
• Meet the following criteria for relapsed or refractory B-cell lymphoma (meet 1 of the first 2 plus 3 below):
• Less than 50% tumor shrinkage or disease progression after 4 courses of standard regimen regulated chemotherapy; relapse after achieving CR after standard regimen chemotherapy; subjects must have received adequate prior therapy, including at least: Anti-CD20 monoclonal antibody; Anthracycline-containing combination chemotherapy. T-cell lymphoma
• Diagnosis of CD7+ refractory/relapsed T-lymphocyte lymphoma confirmed by pathology and histology, meeting any of the following criteria:
• Relapsed: Disease relapse determined after having previously received at least two standardized treatment regimens to achieve complete remission, or disease relapse after having undergone stem cell transplantation to achieve complete remission; Refractory: previous treatment with at least two regimens and failure to achieve complete remission after the last treatment, or failure to achieve remission or disease progression after stem cell transplantation.
• II Acute lymphoblastic leukemia cohort:
• Acute B-lymphoblastic leukemia Refractory/relapsed B-lymphoblastic leukemia diagnosed as CD19+ and/or CD20+ and/or CD22+ and/or BAFF+ confirmed by immunohistochemistry or flow cytometry.
• Refractory/relapsed B-lymphoblastic leukemia (meeting 1 of the following 4 criteria is sufficient):
• Relapse within 6 months of first remission; first refractory without achieving complete remission with 2 cycles of standard chemotherapy regimen; failure to achieve complete remission or relapse after first or multiple lines of salvage chemotherapy; those who are not suitable for HSCT, or who have abandoned HSCT due to medical constraints, or those who have relapsed after HSCT.
• Acute T-lymphoblastic leukemia
• Diagnosis of CD7+ refractory/relapsed T-ALL/LBL confirmed by immunohistochemistry or flow cytometry, meeting any of the following criteria:
• No CR after standard chemotherapy; CR after first treatment, but CR lasted less than 12 months; No CR after first or more remedial therapy; Relapse two or more times.

You may not qualify if:

• a history of severe cardiac insufficiency with a left ventricular ejection fraction \<50%; A history of severe lung function-impairing disease; Combination of other malignant tumors in progressive stages; Combination of severe infections that cannot be effectively controlled; Combination of severe autoimmune disease or congenital immunodeficiency; Active hepatitis (Hepatitis B virus deoxyribonucleic acid \[HBV-DNA\] or Hepatitis C virus ribonucleic acid \[HCV-RNA\] test results above the lower limit of detection); Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), or syphilis infection; History of severe allergy to biological products (including antibiotics); Allogeneic hematopoietic stem cell transplantation patients who still have acute graft-versus-host reaction (GvHD) one month after stopping immunosuppressive drugs; Presence of other serious physical or mental illnesses or abnormal laboratory tests that may increase the risk of participation in the study or interfere with the results of the study, as well as patients who, in the opinion of the investigator, are not suitable for participation in this study.

Sponsors & Collaborators

• Tianjin Medical University General Hospital: lead
• Hebei Taihe Chunyu Biotechnology Co., Ltd: collaborator

Study Sites (1)

TianJin China. TianJin Medical University General

Tianjin, Tianjin Municipality, 300072, China

RECRUITING

MeSH Terms

Conditions

Lymphoma; Leukemia, Myeloid, Acute; Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Leukemia; Hematologic Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Central Study Contacts

Rong Fu

CONTACT

+86 12260817111; yhwhao@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief physician

Study Record Dates

• First Submitted: March 23, 2025
• First Posted: April 4, 2025
• Study Start: November 9, 2024
• Primary Completion: February 28, 2026
• Study Completion (Estimated): February 28, 2027
• Last Updated: April 4, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)