A Study of HY004 Treatment in Adult Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r B-ALL)

Phase 1

Not yet recruiting

• Conditions: B-cell Acute Lymphoblastic Leukemia
• Interventions: Biological: HY004; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate

• Registration Number: NCT06009107
• Lead Sponsor: Juventas Cell Therapy Ltd.

Brief Summary

This is a multi-center, phase I/II trial to evaluate the safety and efficacy of HY004 treatment in Adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-cell ALL).

Detailed Description

This trial is a multi-center, open label, single-arm, phase I/II trial to evaluate the safety and efficacy of HY004 treatment in Adult (aged 18\~65 years old) patients with r/r B-cell ALL.

The phase I part of the trial is to evaluate the safety, optimal dose of HY004, Pharmacokinetics/Pharmacodynamics(PK/PD)and preliminary efficacy in the treatment of Adult patients with r/r B-cell ALL. The phase II part of the trial is to evaluate the efficacy and safety of HY004 in in the treatment of Adult patients with r/r B-cell ALL. The study includes screening, pre-treatment (Cell Product manufacture \& lymphodepletion), HY004 infusion, safety and efficacy follow-up, and survival follow-up. All subjects who have received HY004 infusion will be followed for up to 2 years.

Study Timeline

• Study First Submitted: 2023-08-18
• Study First Submitted QC: 2023-08-18
• Study First Posted: 2023-08-24
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-06
• Last Update Posted: 2025-02-07
• Study Start: 2025-06-30
• Primary Completion: 2026-12-30
• Study Completion: 2027-12-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Signed written informed consent prior to any study procedures (patient and/or parent or legal guardian);
2. Gender is not limited, and the age at the time of screening is ≥ 18 years old and ≤ 65 years old;
3. Relapsed or refractory acute lymphoblastic leukemia (ALL);
4. Documentation of CD19 and/orCD22 tumor expression demonstrated in bone marrow or peripheral blood within 3 months before screening;
5. Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening;
6. ECOG score 0-1 points;
7. Organ function requirements: All patients must have adequate renal and liver functions.

Exclusion Criteria

1. Active Central Nervous System (CNS) involvement by malignancy;
2. Isolated extra-medullary disease relapse;
3. Patients with Burkitt's lymphoma/leukemia;
4. History of concomitant genetic syndrome;
5. Patients with acute graft-versus-host disease (GVHD) or moderate-tosevere chronic GVHD within 4 weeks before screening; Patients with a history of allogeneic hematopoietic stem cell transplantation within 12 weeks before single collection;
6. Active systemic autoimmune disease;
7. Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HbsAg positive) or hepatitis C virus (anti- HCV positive);
8. Patients with active infections at screening;
9. Patients who have used CAR-T cell therapy before screening;
10. Patients with an expected lifespan of less than 3 months.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Participant Group	HY004	Participants with relapsed or refractory B-precursor acute lymphoblastic leukemia (r/r B-ALL) will receive conditioning chemotherapy (fludarabine 25-30 mg/m\^2 intravenously \[IV\] over 30 minutes on Day -5, Day -4, and Day -3 and cyclophosphamide 500 mg/m\^2 IV over 60 minutes on Day -5, Day -4), following a single IV infusion of chimeric antigen receptor (CAR) transduced autologous T cells(HY004).
Participant Group	Cyclophosphamide	Participants with relapsed or refractory B-precursor acute lymphoblastic leukemia (r/r B-ALL) will receive conditioning chemotherapy (fludarabine 25-30 mg/m\^2 intravenously \[IV\] over 30 minutes on Day -5, Day -4, and Day -3 and cyclophosphamide 500 mg/m\^2 IV over 60 minutes on Day -5, Day -4), following a single IV infusion of chimeric antigen receptor (CAR) transduced autologous T cells(HY004).
Participant Group	Fludarabine Phosphate	Participants with relapsed or refractory B-precursor acute lymphoblastic leukemia (r/r B-ALL) will receive conditioning chemotherapy (fludarabine 25-30 mg/m\^2 intravenously \[IV\] over 30 minutes on Day -5, Day -4, and Day -3 and cyclophosphamide 500 mg/m\^2 IV over 60 minutes on Day -5, Day -4), following a single IV infusion of chimeric antigen receptor (CAR) transduced autologous T cells(HY004).

Primary Outcome Measures

Name	Time	Method
Overall Remission Rate (ORR)	at the end of Month 3	ORR is defined as Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi) per NCCN classification, as determined by Independent Review Committee (IRC).

Secondary Outcome Measures

Name	Time	Method
Overall Remission Rate (ORR) with minimal residual disease (MRD) negativity	at the end of Month 3	Overall Remission Rate (ORR) with minimal residual disease (MRD) negativity as determined by IRC and Investigators; MRD negativity as determined using flow cytometry.
Duration of remission (DOR)	to data cutoff date	DOR is defined as the time between their first complete response per independent review to relapse or any death in the absence of documented relapse.
Allogeneic Stem Cell Transplant (Allo-SCT) rate	First infusion date of HY004 to data cutoff date(up to 2 years)	The proportion of patients who have received Allo-SCT after HY004 treatment.
Relapse Free Survival (RFS)	up to 2 years	RFS is defined as the time from the HY004 infusion date to the date of disease relapse or death from any cause.
Overall survival (OS)	2 years	OS is defined as the time from the HY004 Cell Injection infusion to the date of death from any cause.
Overall Remission Rate (ORR)	within 3 months	ORR is defined as Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi) per NCCN classification.
Event-Free Survival(EFS)	up to 2 years	EFS is defined as the time from the HY004 infusion date to the date of any event, including disease progression, cessation of treatment for any reason, or death.
Best overall response (BOR)	up to 2 years	The proportion of patients who have achieved the best response (CR or CRi) after HY004 treatment.
Percentage of Participants Experiencing Treatment-Emergent Adverse Events（TEAE）	up to 2 years	Evaluate the type, frequency, severity of adverse events, and abnormal laboratory test values; Evaluate the frequency and severity of adverse events related to HY004.