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

Sponsor
Beijing Boren Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT05032599
Collaborator
(none)
18
1
1
35.6
0.5

Study Details

Study Description

Brief 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/m2/day and cyclophosphamide at 250 mg/m2/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:

2×106 (±20%). If the manufactured cells were not sufficient to meet the preassigned standard dose criteria, patients are given infusion at a low dose of 5×105 (±20%) /kg.

Condition or Disease Intervention/Treatment Phase
  • Biological: CD5 CART
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
18 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Sep 14, 2021
Anticipated Primary Completion Date :
Sep 1, 2022
Anticipated Study Completion Date :
Sep 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: CD5 CART

All patients who receive CD5 CART cell infusion

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.

Outcome Measures

Primary Outcome Measures

  1. Incidence and type of dose-limiting toxicity (DLT) [21 days post intravenous injection]

  2. Incidence and severity of adverse events (AE) [30 days post intravenous injection]

Secondary Outcome Measures

  1. Objective response rate (ORR) [30 days post infusion]

    Objective response rate (ORR) according to NCCN, Complete response(CR),CR with incomplete blood count recovery(CRi) .

  2. Quantification of CAR T cells [2 years post infusion]

    Quantification of CAR T cells by flow cytometry and/or quantitative PCR in peripheral blood and cerebral spinal fluid (CSF).

  3. Severe adverse events (SAE) [2 years post infusion]

    The incidence of any severe adverse event (SAE) and the severity of SAE from day 30 to 2 years.

  4. Best overall response (BOR) [3 months post infusion]

    Best overall response (BOR) rate at 3 months.

Eligibility Criteria

Criteria

Ages Eligible for Study:
1 Year to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Beijing Boren Hospital Beijing Beijing China 100070

Sponsors and Collaborators

  • Beijing Boren Hospital

Investigators

  • Principal Investigator: Jing Pan, Master, Beijing Boren Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Beijing Boren Hospital
ClinicalTrials.gov Identifier:
NCT05032599
Other Study ID Numbers:
  • BRYY-IIT-LCYJ-2021-015
First Posted:
Sep 2, 2021
Last Update Posted:
May 2, 2022
Last Verified:
Apr 1, 2022
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Beijing Boren Hospital
Additional relevant MeSH terms:

Study Results

No Results Posted as of May 2, 2022