CD5 Chimeric Antigen Receptor (CAR) T Cells in Subjects With Relapsed or Refractory T-Cell Acute Lymphoblastic Leukemia

CD5 Chimeric Antigen Receptors (CAR) T Cells in Subjects With Relapsed or Refractory T-Cell Acute Lymphoblastic Leukemia: a Single-center, Open-label, Non-randomized, Phase 1/2 Clinical Trial

This is a single-center, open-label, non-randomized, phase 1/2 study of anti-CD5 CAR-T cell therapy in patients with CD5+ relapsed or refractory T-cell malignancies. A bayesian optimal interval (BOIN) 12 design will be used to explore the optimal biological dose (OBD) from starting dose level 1: 1×10^6 (±20%) to dose level 2: 2×10^6 (±20%) in three cohorts (autologous, previous-transplant-donor or newly matched donor-derived CD5 CAR T cells). If the manufactured cells are not sufficient to meet the preassigned standard dose criteria, patients will be given infusion at a low dose level of 5×10^5 (±20%) /kg. The primary objective is to evaluate the safety and tolerability of CD5 CAR T cell therapy in subjects, determine the OBD and recommend phase 2 dose (RP2D) in phase 1, and evaluate the efficacy of CD5 CAR T cell therapy in phase 2. The primary endpoint is the type and incidence of dose-limiting toxicity (DLT) within 28 days, and the incidence and severity of adverse events (AEs) within 30 days after CD5 CAR T-cell infusion in phase 1, the best overall response (BOR) at 3 months (± 1 week) after CD5 CAR T-cell infusion in phase 2. A total number of 54 subjects will be enrolled.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Lymphoblastic Leukemia, in Relapse; Refractory Acute Lymphoblastic Leukemia; T-Cell Acute Lymphocytic Leukemia
• Intervention / Treatment: Drug: Autologous CD5 CAR T-cells; Drug: Newly matched donor-derived CD5 CAR T-cells; Drug: Previous stem-cell transplantation (SCT) donor-derived CD5 CAR T-cells

• Study Type: Interventional
• Enrollment (Estimated): 54
• Phase: Phase 2; Phase 1

Contacts and Locations

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

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:

1. Candidates with relapse or refractory CD5+ T-cell malignancies, who have progressed after treatment with all standard therapies or been intolerant of standard care, have limited prognosis with currently available therapies and have no available curative treatment options (such as stem-cell transplantation (SCT) or chemotherapy);
2. For subjects who received autologous CD5 CAR T cells, the tumor burden in peripheral blood is less than 20%, and suspending anti-neoplastic treatment for more than 2 weeks;
3. Aged 1-70 years;
4. No severe allergy;
5. Eastern Cooperative Oncology Group (ECOG) performance status 1 score 0 to 2;
6. Patients are expected to live for at least 60 days;
7. CD5+ on blasts in bone marrow (BM) or cerebrospinal fluid (CSF) and tumor tissues by flow cytometry and immunohistochemistry, respectively. (Positive rate >80% by flow cytometry with less than one log difference in mean fluorescence intensity from normal T cells, or positive rate >30% positive by immunohistochemistry);
8. Provide a signed informed consent before any screening procedure. Subjects who voluntarily participate in the study should have the ability to understand and sign the informed consent form and be willing to follow the study visit schedule and relevant study procedure, as specified in the protocol. Candidates aged 19-70 years need to be sufficiently conscious and able to sign the treatment consent form and voluntary consent form. Children candidates of 8-18 years old need to be sufficiently conscious and able to sign the treatment consent form and voluntary consent form and their legal guardian or patient advocate has also need to sign the treatment consent form and voluntary consent form, respectively. Children candidates of 1-7 can be recruited after the legal guardian or patient advocate has signed the treatment consent form and voluntary consent form;
9. Have available allogeneic hematopoietic stem cell transplantation donor for the subject who received newly matched donor-derived CD5 CAR T cells, and is willing to perform SCT when CR is achieved.

Exclusion Criteria:

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

1. Impaired consciousness or intracranial hypertension;
2. Symptomatic congestive heart failure or severe cardiac arrhythmia;
3. Manifestations of severe respiratory system failure;
4. Co-existence with other malignancies;
5. Disseminated intravascular coagulation;
6. Serum creatinine and/or blood urea nitrogen (BUN) ≥ 1.5-fold upper limit;
7. Sepsis or other uncontrollable infections;
8. Uncontrollable diabetes;
9. Serious mental illness;
10. Apparent and active intracranial lesions on cranial magnetic resonance imaging (MRI);
11. Underwent organ transplantation, excepting SCT;
12. Pregnant females;
13. Positive test for infectious hepatitis, acquired immune deficiency syndrome (AIDS) or syphilis;
14. Post-CAR SCT is not feasible in patients who plan to receive newly matched donor-derived CD5 CAR T cells;
15. Inability to collect peripheral blood mononuclear cells (PBMC) or no frozen PBMC available for CAR T cell manufacturing.

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: Autologous CD5 CAR T-cells; After a lymphodepleting regimen, the patients will receive autologous CD5 CAR T-cell infusion.	Drug: Autologous CD5 CAR T-cells; Peripheral blood mononuclear cells for the production of CD5 CAR T-cells from patients.
Experimental: Newly matched donor-derived CD5 CAR T-cells; After a lymphodepleting regimen, the patients will receive newly matched donor-derived CD5 CAR T-cell infusion.	Drug: Newly matched donor-derived CD5 CAR T-cells; Peripheral blood mononuclear cells for the production of CD5 CAR T cells are collected from newly matched donors.
Experimental: Prior stem-cell transplantation (SCT) donor-derived CD5 CAR T-cells; After a lymphodepleting regimen, the patients will receive prior SCT donor-derived CD5 CAR T-cell infusion.	Drug: Previous stem-cell transplantation (SCT) donor-derived CD5 CAR T-cells; Peripheral blood mononuclear cells for the production of CD5 CAR T cells are collected from previous SCT donors.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1-The incidence and type of dose-limiting toxicity (DLT)	The number of patients experiencing dose-limiting toxicity (DLT) will be evaluated and the type of DLT will be recorded.	28 days after CD5 CAR T cell infusion
Phase 1-The incidence and severity of adverse events (AEs)	The number of patients experiencing adverse events (AEs) and the severity of AEs will be evaluated.	30 days after CD5 CAR T cell infusion
Phase 2-Antitumor effect	Assessment of best overall response (BOR) rate. BOR rate is the percentage of patients with the best overall response in complete response (CR), complete response with incomplete hematological recovery (CRi) or partial response (PR) based on the National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2023 of Acute Lymphoblastic Leukemia.	3 months (± 1 week) after CD5 CAR T infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1-Objective response rate (ORR)	Objective response rate (ORR) is the percentage of subjects who have achieved CR, CRi or PR based on the National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2023 of Acute Lymphoblastic Leukemia.	30 days after CD5 CAR T cell infusion
Phase 1-Pharmacokinetics of CD5 CAR T cells	The proliferation and survival of CAR T cells will be measured by flow cytometry and quantitative polymerase chain reaction (qPCR).	Up to 2 years after CD5 CAR T cell infusion
Phase 1-The incidence and severity of adverse events (AEs).	The number of patients experiencing adverse events (AEs) and the severity of AEs will be evaluated.	From 30 days to 2 years after CD5 CAR T cell infusion
Phase 1-Best overall response (BOR) rate.	BOR rate is the percentage of patients with the best overall response in CR, CRi or PR based on the National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2023 of Acute Lymphoblastic Leukemia.	3 months (± 1 week) after CD5 CAR T cell infusion
Phase 2-Objective response rate (ORR)	Objective response rate (ORR) is the percentage of subjects who have achieved CR, CRi or PR based on the National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2023 of Acute Lymphoblastic Leukemia.	1 months and 3 months after CD5 CAR T cell infusion
Phase 2- The incidence and severity of AEs	The number of patients experiencing adverse events (AEs) and the severity of AEs will be evaluated.	Up to 2 years
Phase 2- Progression free survival (PFS)	Progression-free survival (PFS) is defined as the time from the initial CD5 CAR T cell infusion to the date of progression or death for any cause.	Up to 2 years
Phase 2- Overall survival (OS).	Overall survival (OS) is defined the time from the initial CD5 CAR T cell infusion to death for any cause.	Up to 2 years

Collaborators and Investigators

• Sponsor: Beijing GoBroad Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 20, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: March 10, 2024
• First Submitted That Met QC Criteria: March 15, 2024
• First Posted (Actual): March 19, 2024

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 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-2024-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No