Autologous and Donor-derived CD7 CAR-T Therapy in Refractory or Relapsed T-cell Acute Lymphoblastic Leukemia/Lymphoma

Autologous and Donor-derived CD7 CAR T-cell Therapy in Refractory or Relapsed T-cell Acute Lymphoblastic Leukemia/Lymphoma: a Single-center, Open-label, Phase Ⅰ/Ⅱ Clinical Trial

This is a single-center, open-label, non-randomized, phase I/II trial. Patients with refractory or relapsed T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/T-LBL) will receive autologous, prior-HSCT donor-derived or new donor-derived CD7 CAR T cells according to their HSCT history, peripheral blood leukemia burden and at their discretion. The primary objective is to learn about the safety of autologous, prior-HSCT donor-derived and new donor-derived CD7 CAR T-cell therapy in patients with refractory or relapsed T-cell acute lymphoblastic leukemia and lymphoma (r/r T-ALL/T-LBL) in phase I and to learn about the efficacy of autologous, prior-HSCT donor-derived and new donor-derived CD7 CAR T-cell therapy in patients with refractory or relapsed T-cell acute lymphoblastic leukemia and lymphoma (r/r T-ALL/T-LBL) in phase II. The primary endpoint is type and incidence of dose limiting toxicity (DLT) within 21 days after CD7 CAR T-cell infusion in phase I and overall response rate (ORR), which includes CR, CRh, CRi, MLFS, aplastic marrow for blood and bone marrow; central nervous system (CNS) remission; CR and PR for lymphomatous extramedullary disease according to National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2023 of Acute Lymphoblastic Leukemia at 3 months (± 1 week) post CD7 CAR T-cell infusion in refractory or relapsed T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/T-LBL) patients treated with CD7 CAR T cells in phase II. A total number of 80 subjects will be enrolled.

Study Overview

• Status: Recruiting
• Conditions: Acute Lymphoblastic Leukemia, in Relapse; Refractory Acute Lymphoblastic Leukemia; T-cell Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Autologous CD7 CAR T-cell; Drug: Prior-HSCT donor-derived CD7 CAR T-cell; Drug: New donor-derived CD7 CAR T-cell

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Tengyu Wang; Phone Number: 86+18333186020; Email: tengyu.wang@gohealtharo.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 102206
      • Recruiting
      • Beijing GoBroad Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Only patients who meet all the following criteria can be included in the group:

1. CD7-positive refractory or relapsed T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/T-LBL) with progression or intolerance after all standard treatments, limited prognosis from currently available treatments and no available treatment options (e.g. HSCT or chemotherapy).
2. Tumor cells in bone marrow or cerebrospinal fluid are positive for CD7 antigen by flow cytometry or tumour tissue is positive for CD7 by immunohistochemistry (CD7 antigen positivity by flow cytometry: >80% of tumour cells expressing CD7 with a mean fluorescence intensity [MFI] of CD7 similar to that of normal T cells are considered to have fully positive expression; >80% of tumor cells expressing CD7 but with an MFI of CD7 at least 1 log lower than that of normal T cells are considered to have low expression [dim]; tumor cells with a CD7 expression rate between 20-80% are considered to have partial expression; CD7 antigen positivity by pathological immunohistochemistry: >30%);
3. Male or female, age 1-70 years;
4. No severe allergic constitution;
5. Eastern Cooperative Oncology Group (ECOG) performance status score (Oken et al., 1982) of 0-2;
6. Life expectancy of at least 60 days as determined by the investigator;
7. Provide a signed informed consent form prior to any screening procedures; subjects volunteering to participate in the study should be capable of understanding and signing the informed consent form and be willing to follow the study visit schedule and associated study procedures as specified in the protocol. Subjects aged 19-70 years old need to be sufficiently aware and capable of signing the informed consent form; subjects aged 1-7 years can be recruited after legal guardians or patient advocates sign the informed consent form; subjects aged 8-18 years need to be sufficiently aware and able to sign the informed consent form, and their legal guardians or patient advocates also need to sign the informed consent form.

Exclusion Criteria:

Patients with at least one of the following conditions are excluded:

1. Intracranial hypertension or unconscious;
2. Acute heart failure or severe arrhythmia;
3. Acute respiratory failure;
4. Other types of malignant tumors;
5. Diffuse intravascular coagulation;
6. Serum creatinine and/or blood urea nitrogen over 1.5 times the normal value;
7. Sepsis or other uncontrolled infection;
8. Uncontrolled diabetes mellitus;
9. Severe psychological disorder;
10. Obvious cranial lesions by cranial MRI;
11. Allergic constitution;
12. Organ recipients;
13. Pregnant or breastfeeding;
14. Active, uncontrolled infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or treponema pallidum (TP).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm-1; Autologous CD7 CAR T-cell treatment	Drug: Autologous CD7 CAR T-cell; Peripheral blood mononuclear cells for the production of CD7 CAR T cells are collected from patients.
Experimental: Arm-2; Prior-HSCT donor-derived CD7 CAR T-cell treatment	Drug: Prior-HSCT donor-derived CD7 CAR T-cell; Peripheral blood mononuclear cells for the production of CD7 CAR T cells are collected from prior-HSCT donors.
Experimental: Arm-3; New donor-derived CD7 CAR T-cell treatment	Drug: New donor-derived CD7 CAR T-cell; Peripheral blood mononuclear cells for the production of CD7 CAR T cells are collected from new donors.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-Limiting Toxicity (DLT) in phase I	Type and incidence of dose-limiting toxicity (DLT) within 21 days after CD7 CAR T-cell infusion	21 days post infusion
Overall Response Rate (ORR) in phase II	Overall response rate (ORR), which includes CR, CRh, CRi, MLFS, aplastic marrow for blood and bone marrow; central nervous system (CNS) remission; CR and PR for lymphomatous extramedullary disease per National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2023 of Acute Lymphoblastic Leukemia at 3 months (± 1 week) post CD7 CAR T-cell infusion in refractory or relapsed T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/T-LBL) patients treated with CD7 CAR T cells	3 months (± 1 week) post infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) in phase I	Overall response rate (ORR), which includes CR, CRh, CRi, MLFS, aplastic marrow for blood and bone marrow; central nervous system (CNS) remission; CR and PR for lymphomatous extramedullary disease per National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2023 of Acute Lymphoblastic Leukemia at 3 months (± 1 week) post CD7 CAR T-cell infusion in refractory or relapsed T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/T-LBL) patients treated with CD7 CAR T cells	3 months (± 1 week) post infusion
Safety in phase II	The adverse events in refractory or relapsed T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/T-LBL) patients treated with CD7 CAR T cells will be assessed according to the 2019 Consensus on Cytokine Release Syndrome and Immune-cell-associated Neurotoxicity published by the American Society of Transplantation and Cell Therapy (ASTCT), the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 and EBMT 2019 consensus.	2 years post infusion
Progression-Free Survival (PFS) in phase II	Progression-free survival (PFS) in refractory or relapsed T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/T-LBL) patients treated with CD7 CAR T cells.	2 years post infusion
Duration of Remission (DOR) in phase II	Duration of remission (DOR) in refractory or relapsed T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/T-LBL) patients treated with CD7 CAR T cells.	2 years post infusion
Overall Survival (OS) in phase II	Overall survival (OS) in refractory or relapsed T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/T-LBL) patients treated with CD7 CAR T cells.	2 years post infusion
Levels of CD7 CAR-T Cells in phase II	Levels of CD7 CAR-T cells in refractory or relapsed T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/T-LBL) patients treated with CD7 CAR T cells	2 years post infusion
Levels of CAR transgene in phase II	Levels of CAR transgene in refractory or relapsed T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/T-LBL) patients treated with CD7 CAR T cells	2 years post infusion
Levels of immune cells in phase II	Levels of immune cells in refractory or relapsed T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/T-LBL) patients treated with CD7 CAR T cells	2 years post infusion
Levels of cytokines in phase II	Levels of cytokines in refractory or relapsed T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/T-LBL) patients treated with CD7 CAR T cells	2 years post infusion

Collaborators and Investigators

• Sponsor: Beijing GoBroad Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2024
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): March 30, 2028

Study Registration Dates

• First Submitted: March 8, 2024
• First Submitted That Met QC Criteria: March 14, 2024
• First Posted (Actual): March 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

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; Hematologic Diseases; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: BJGBYY-IIT-LCYJ-2024-003

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