Safety, Tolerability, and Pharmacokinetics of Donor-derived CD19 CAR Therapy Bridged Allo-HSCT and Sequential Donor-derived CD22 CAR Therapy for r/r B-ALL: a Clinical Trial

B-cell Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Safety, Tolerability and Pharmacokinetics of Donor-derived CD19 CAR Therapy Bridged Allogeneic Haematopoietic Stem Cell Transplantation and Sequential Donor-derived CD22 CAR Therapy in Refractory or Relapsed B Cell Acute Lymphoblastic Leukemia: a Clinical Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06326008
• Other study ID #: BJGBYY-IIT-LCYJ-2023-002
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: June 15, 2024
• Est. completion date: December 30, 2026

Study information

• Verified date: May 2024
• Source: Beijing GoBroad Hospital
• Contact: Tengyu Wang
• Phone: 86+18333186020
• Email: tengyu.wang[@]gohealtharo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an investigator-initiated, single-arm, open-label, non-randomised phase I clinical study. The objective of this trial is to evaluate the safety, tolerability and pharmacokinetics of donor-derived CD19 CAR Therapy bridged Allo-HSCT and sequential donor-derived CD22 CAR Therapy for r/r B-ALL and to explore the efficacy of this therapy preliminarily. The primary endpoints are incidence and type of dose-limiting toxicity (DLT) within 28 days (i.e., 43 days after donor-derived CD19 CAR T-cell infusion) after donor-derived CD19 CAR T-cell therapy bridged allogeneic haematopoietic stem cell transplantation; total number, incidence and severity of adverse events from donor-derived CD19 CAR T cell infusion back to 30 days after donor-derived CD22 CAR T cell infusion (i.e., within 120 days of donor-derived CD19 CAR T cell infusion). The secondary endpoints are total number, incidence and severity of adverse events from 120 days to 2 years after donor-derived CD19 CAR T-cell infusion; ORR(CR+CRi) on days 45, 90, 120; duration of response(DOR), event-free survival(EFS), overall survival(OS); pharmacokinetics characteristics. The trial plan to enroll 3~12 cases in dose escalation phase and 36 cases in dose expansion phase.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 48
• Est. completion date: December 30, 2026
• Est. primary completion date: June 15, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 18 Years

Eligibility

Inclusion Criteria:

• Patients will be enrolled only if they meet all the inclusion criteria.

1. Patients with relapsed or refractory CD19+/CD22+ (FCM >95%) B-cell acute lymphoblastic leukaemia who have progressed despite or are intolerant to all standard therapies, including, but not limited to, immunotherapies such as Blinatumomab (BITE), Tyrosine kinase inhibitors (TKI), CAR T-cell therapy, etc.; Currently available therapies have a limited prognosis and there are no available curative treatment options (e.g., HSCT or chemotherapy);

2. Peripheral blood tumour burden =60% or severe peripheral blood cytopenia, unsuitable/unable to collect autologous lymphocytes;

3. 1 to 18 years old;

4. Patient's expected survival time = 60 days;

5. Physical status: ECOG score 0-2;

6. Availability of allogeneic donors (HLA-identical or HLA-haploidentical) DSA-negative for collection of peripheral blood mononuclear cells and peripheral blood stem cells;

7. Sign an informed consent form during the screening period. Pediatric patients under 8~18 years of age need to have sufficient awareness to voluntarily sign an informed consent form, and their legal representatives (guardians) also need to voluntarily sign an informed consent form; pediatric patients aged 1~7 years can only be recruited after their legal guardians have voluntarily signed an informed consent form.

Exclusion Criteria:

• Patients who meet any of the following criteria are not eligible for enrolment.

1. Patients who have received previous haematopoietic stem cell transplantation (including peripheral blood haematopoietic stem cell transplantation and bone marrow haematopoietic stem cell transplantation);

2. Intracranial hypertension or cerebral impaired consciousness;

3. Symptomatic heart failure or severe cardiac arrhythmia;

4. Symptoms of severe respiratory failure;

5. With other types of malignant tumours;

6. Diffuse intravascular coagulation;

7. Serum creatinine and/or urea nitrogen = 1.5 times the normal value;

8. Suffering from sepsis or other uncontrollable infections;

9. Suffering from uncontrollable diabetes mellitus;

10. Severe mental disorders;

11. Have significant intracranial lesions on cranial MRI (excluding intracranial masses caused by central nervous system leukaemia);

12. Have organ transplant history;

13. Female patients (patients of childbearing potential) with positive blood HCG test;

14. Hepatitis (including Hepatitis B and Hepatitis C) and positive screening for AIDS and syphilis;

15. No allogeneic donor suitable for collection of peripheral blood lymphocytes and haematopoietic stem cells.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia, in Relapse
• B-cell Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Donor-derived CD19 CAR Therapy Bridged Allo-HSCT and Sequential Donor-derived CD22 CAR Therapy
Peripheral blood mononuclear cells for the production of CD19 CAR T cells and CD22 CAR T cells are collected from donors and haematopoietic stem cells are collected from donors.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Beijing GoBroad Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity (DLT)	Incidence and type of dose-limiting toxicity (DLT) within 28 days (i.e., 43 days after donor-derived CD19 CAR T-cell infusion) after donor-derived CD19 CAR T-cell therapy bridging allogeneic haematopoietic stem cell transplantation will be recorded.	Within 43 days of donor-derived CD19 CAR T-cell infusion
Primary	Adverse events (AEs)	Total number, incidence and severity of adverse events (AEs) from the time of donor-derived CD19 CAR T cell infusion back to 30 days after donor-derived CD22 CAR T cell infusion (i.e., within 120 days of donor-derived CD19 CAR T-cell infusion) will be recorded.	Within 120 days of donor-derived CD19 CAR T-cell infusion
Secondary	Long-term Adverse events (AEs)	Total number, incidence and severity of AEs from 120 days to 2 years after donor-derived CD19 CAR T-cell infusion will be recorded.	From 120 days to 2 years after donor-derived CD19 CAR T-cell infusion
Secondary	Objective response rate(ORR)	Objective response rate (ORR) at day 30, day 45, day 90 as determined by the National Comprehensive Cancer Network (NCCN) GuidelinesVersion 3.2023 of Acute Lymphoblastic Leukemia.	day 30, day 45, day 90
Secondary	Duration of response (DOR)	DOR is defined as the date when CR or CRi response criteria are first met to the date of relapse or death caused by ALL in the absence of documented relapse.	Up to 2 years
Secondary	Event-free survival (EFS)	EFS is defined as the time from donor-derived CD19 CAR T-cell infusion to the occurrence of any event, which includes disease progression, discontinuation of therapy for any reason, or death.	Up to 2 years
Secondary	Overall survival (OS)	OS is defined as the time from the infusion of donor-derived CD19 CAR T cells until death due to any cause.	Up to 2 years
Secondary	The persistence of CD19/CD22 CAR T cells.	The persistence of CD19/CD22 CAR T cells in cerebral spinal fluid (CSF) and peripheral blood will be detected by flowcytometry and qPCR after CD19/CD22 CAR T cells infusion.	Up to 2 years
Secondary	The Maximum concentration (Cmax) of CD19/CD22 CAR T cells.	The Maximum concentration (Cmax) of CD19/CD22 CAR T cells will be recorded.	Up to 2 years
Secondary	The time to maximum plasma concentration (Tmax) of CD19/CD22 CAR T cells.	The time to maximum plasma concentration (Tmax) of CD19/CD22 CAR T cells will be recorded.	Up to 2 years