Anti-TRBC1 CAR-T Cell Therapy in Patients With TRBC1 Positive T Cell Malignancies

The Safety and Clinical Efficacy of Human TRBC1 CAR-T Cell Therapy for Patients With Relapsed/Refractory TRBC1 Positive T Cell Hematological Maliganacies

The purpose of this study is to evaluate the safety and efficacy of CAR T cell treatment targeting TRBC1 in patients with relapsed or refractory TRBC1 positive T-cell hematological maliganacies

Study Overview

• Status: Suspended
• Conditions: Angioimmunoblastic T-cell Lymphoma; Peripheral T Cell Lymphoma; Anaplastic Lymphoma; Acute T Cell Leukemia; T-lymphoblastic Lymphoma
• Intervention / Treatment: Drug: anti-TRBC1 CAR-T cell therapy

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200080
      • Xianmin Song

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

(1)18 to 70 Years Old, Male and female; (2) Expected survival > 12 weeks; (3) ECOG score 0-2; (4) Confirmed diagnosis of acute T cell leukemia and screened for TRBC1 positive, including following conditions:

1. Patients who do not get a CR with ≥2 prior lines of therapy
2. Those who achieves CR, but have a early relapse(<12months),or a late relapse (>=12months) failing to acheive a CR after 1 line salvage chemotherapy
3. For any Patiens failed ASCT/allo-SCT (5) Relapsed and refractory patients with diagnosis of T cell lymphoma have had≥2 prior lines of therapy,including:

a. Peripheral T cell lymphoma NOS, or b. Angioimmunoblastic T cell lymphoma, or c. Anaplastic large cell lymphoma (6) Confirmed T lymphoblatic lymphoma

1. Patients who do not get a CR with ≥2 prior lines of therapy
2. Relapsed patients failing to acheive a CR after 1 line salvage chemotherapy
3. For any Patiens failed ASCT/allo-SCT (7) The venous access required for collection can be established and mononuclear cell collection can be determined by the investigators; (8) Liver, kidney and cardiopulmonary functions meet the following requirements:

a. Ccr≥60mL/min(Cockcroft Gault) b. Left ventricular ejection fraction >50%; c. Baseline oxygen saturation>92%; d. Total bilirubin ≤ 1.5×ULN; e. ALT and AST ≤ 3×ULN; (9) Able to understand and sign the In

Exclusion Criteria:

1. Malignant tumors other than acute lymphoblastic leukemia within 5 years prior to screening, in addition to adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical resection, and ductal carcinoma in situ after radical resection;
2. Uncontrolled infection;patients with positive HBsAg or HBcAb and peripheral blood HBV DNA titer detection ≥ 1 × 10^2 copy number / L; HCV antibody positive and peripheral blood HCV RNA positive; HIV antibody positive; CMV DNA positive; syphilis positive;
3. Any instability of systemic disease, including but not limited to unstable angina, cerebrovascular accident, or transient cerebral ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure (New York heart association (NYHA) classification ≥ III), need drug therapy of severe arrhythmia, liver, kidney, or metabolic disease;
4. Any uncontrolled disease may affect entry
5. Current or history of CNS involvement by malignancy.Known history or presence of clinically relevant central nervous system (CNS) pathology. Patients with a known history or prior diagnosis other immunologic or inflammatory disease affecting the CNS (such as epilepsy)
6. Patients who are receiving systemic steroid treatment and requiring long-term systemic steroid treatment during the treatment as determined by the investigator before screening (except inhalation or topical use); And subjects treated with systemic steroids (except inhalation or topical use) within 72h prior to cell transfusion;
7. Pregnant or lactating woman, and female subject who plans to have a pregnancy within 1 year after cell transfusion, or male subject whose partner plans to have a pr egnancy within 1 year after cell transfusion;
8. Active or uncontrollable infection requiring systemic therapy
9. Received CAR-T treatment or other gene therapies before enrollment;
10. Kown be allergic to anti-TRBC1 CAR-T cells or drugs(Fludarabine or Cyclophophamide)
11. The investigators consider other conditions unsuitable for enrollment.
12. Patients who may not be able to sign the Informed Consent due to disease,or who do not understand or unwillingness or inability to comply with research requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: anti-TRBC1 CAR-T cell; Administration with anti-TRBC1 CAR-T cells in the relapsed/refractory T cell hematological malignancy patients.	Drug: anti-TRBC1 CAR-T cell therapy; TRBC1 positve patients with relapsed or refractory T cell malignacy will receive CAR-T cell therapy targetting TRBC1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability	Safety measured by occurence of study related adverse effects defined by NCI CTCAE5.0	28 days post infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CAR-T cell expansion and persistence	To evaluate anti-TRBC1 CAR-T cell expansion and persistence after infusion	2 years post infusion
Total response rate (ORR) after administration	CR+CRi for T-ALL CR+PR for T cell lyphoma	3 months post infusion
Duration of remission (DOR) after administration	Duration of remission (DOR) after administration	2 years post infusion
Overall Survival (OS)after administration	Overall Survival (OS)after administration	2 years post infusion
Progression Free Survival (PFS) after infusion	Progression Free Survival (PFS) after infusion	2 years after infusion

Collaborators and Investigators

• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2021
• Primary Completion (Estimated): November 26, 2023
• Study Completion (Estimated): November 26, 2023

Study Registration Dates

• First Submitted: March 31, 2021
• First Submitted That Met QC Criteria: March 31, 2021
• First Posted (Actual): April 1, 2021

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 26, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Leukemia, Lymphoid; Leukemia; Lymphadenopathy; Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Leukemia, T-Cell; Immunoblastic Lymphadenopathy; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: SHYSXY-202101-CART

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No