Donor-Derived CD5 CAR T Cells in Subjects With Relapsed or Refractory T-Cell Acute Lymphoblastic Leukemia

T-Cell Acute Lymphoblastic Leukemia Clinical Trial

Official title:

First-in-Human (FIH), Open-Label, Non-Randomized, Single-Arm Phase 1 Study to Evaluate the Safety and Tolerability of Donor-Derived CD5 CAR T Cells in Subjects With Relapsed or Refractory T-Cell Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05032599
• Other study ID #: BRYY-IIT-LCYJ-2021-015
• Status: Recruiting
• Phase: Phase 1
• Start date: September 14, 2021
• Est. completion date: September 1, 2024

Study information

• Verified date: February 2023
• Source: Beijing Boren Hospital
• Contact: Jing Pan, Master
• Phone: +8618911067969
• Email: panj[@]borenhospital.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a FIH, single center, open label, non-randomized, single-arm, Phase I clinical trial to evaluate the safety and tolerability of CD5 CAR T cells in subjects with relapsed or refractory T-cell acute lymphoblastic leukemia. At least 18 subjects will be enrolled. After the collection of PBMC and about 5 days before infusion, lymphodepletion (fludarabine at 30 mg/m^2/day and cyclophosphamide at 250 mg/m^2/day; for prior-SCT donor-derived CAR T-cell infusion) or intensified lymphodepletion (fludarabine at 30 mg/m^2/day and cyclophosphamide at 30 mg/kg/day; for new donor-derived CAR T-cell infusion) will be administrated for 3 days. Then this study will be using BOIN1/2 approach from starting dose 1: 1×10^6 (±20%) to dose 2: 2×10^6 (±20%). If the manufactured cells were not sufficient to meet the preassigned standard dose criteria, patients are given infusion at a low dose of 5×10^5 (±20%) /kg.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: September 1, 2024
• Est. primary completion date: September 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 70 Years

Eligibility

Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the

following criteria:

1. Candidates with relapse or refractory CD5+ T cell acute lymphoblastic leukemia, who have progressed on after treatment with all standard therapies or intolerant of standard care, have limited prognosis with currently available therapies and had no available curative treatment options (such as SCT or chemotherapy)

2. Male or female, aged 1-70 years

3. No serious allergic constitution

4. Eastern Cooperative Oncology Group (ECOG) performance status (Oken et al., 1982) score 0 to 2

5. Have life expectancy of at least 60 days based on investigator's judgement

6. CD5 positive in bone marrow or cerebrospinal fluid (CSF) by flow cytometry, or CD5 positive in tumor tissues by immunohistochemistry; (CD5 positive criteria: Flow cytometry: Positive: > 80% of tumor cells expressed CD5 and the MFI of CD5 is the same as that in normal T cells; Dim: > 80% of tumor cells expressed CD5, but the MFI of CD5 is lower than that in normal T cells as least as 1log; Partial positive: 20-80% of tumor cells expressed CD5 and the MFI of CD5 is the same as that in normal T cells. tumor tissue immunohistochemistry: Positive > 30% tumor cells expressed CD5);

7. 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.

8. Have suitable and available allogeneic hematopoietic stem cell transplantation donor, and is willing to proceed to SCT if achieve CR. Exclusion Criteria: An individual who meets any of the following criteria will be excluded from participation

in this study:

1. Intracranial hypertension or disorder of consciousness

2. Symptomatic heart failure or severe arrhythmia

3. Symptoms of severe respiratory failure

4. Complicated with other types of malignant tumors

5. Diffuse intravascular coagulation

6. Serum creatinine and / or blood urea nitrogen = 1.5 times of the normal value

7. Suffering from septicemia or other uncontrollable infections

8. Patients with uncontrollable diabetes

9. Severe mental disorders

10. Obvious and active intracranial lesions were detected by cranial magnetic resonance imaging (MRI)

11. Have received organ transplantation (excluding bone marrow transplant)

12. Reproductive-aged female patients with positive blood HCG test

13. Screened to be positive of infection of hepatitis (including hepatitis B and C), AIDS or syphilis

14. Post-CAR SCT is not feasible in patients who plan to receive new-donor derived CD5 CAR T cells

15. No donor is applicable for peripheral blood mononuclear cell (PBMC) collection or no frozen donor's PBMC is available for manufacturing CAR T cells.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
• T-Cell Acute Lymphoblastic Leukemia

Intervention

Biological:
• CD5 CART
Subjects will be pretreated with chemotherapy prior to infusion of CAR T cells: After the collection of PBMC and about 5 days before infusion, lymphodepletion (fludarabine at 30 mg/m^2/day and cyclophosphamide at 250 mg/m^2/day; for prior-SCT donor-derived CAR T-cell infusion) or intensified lymphodepletion (fludarabine at 30 mg/m^2/day and cyclophosphamide at 30 mg/kg/day; for new donor-derived CAR T-cell infusion) will be administrated for 3 days.

Locations

Country	Name	City	State
China	Beijing Boren Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Boren Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and type of dose-limiting toxicity (DLT)		21 days post intravenous injection
Primary	Incidence and severity of adverse events (AE)		30 days post intravenous injection
Secondary	Objective response rate (ORR)	Objective response rate (ORR) according to NCCN, Complete response(CR),CR with incomplete blood count recovery(CRi) .	30 days post infusion
Secondary	Quantification of CAR T cells	Quantification of CAR T cells by flow cytometry and/or quantitative PCR in peripheral blood and cerebral spinal fluid (CSF).	2 years post infusion
Secondary	Severe adverse events (SAE)	The incidence of any severe adverse event (SAE) and the severity of SAE from day 30 to 2 years.	2 years post infusion
Secondary	Best overall response (BOR)	Best overall response (BOR) rate at 3 months.	3 months post infusion