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

B-cell Acute Lymphoblastic Leukemia Clinical Trial

— B-ALL  

Official title:

A Phase I/II, Single Arm, Multi-center Study Evaluating the Safety and Efficacy of HY004 in Adult Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r B-ALL)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06009107
• Other study ID #: HY004101
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: August 31, 2024
• Est. completion date: December 30, 2026

Study information

• Verified date: March 2024
• Source: Juventas Cell Therapy Ltd.
• Contact: JunYin Yu PM
• Phone: +86-010-65960098
• Email: yujunyin[@]juventas.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: December 30, 2026
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Biological:
• HY004
A single infusion of Autologous 2nd generation CD19/CD22-directed CAR-T cells administered intravenously.

Drug:
• Cyclophosphamide
Administered intravenously.
• Fludarabine Phosphate
Administered intravenously.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Juventas Cell Therapy Ltd.

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	In vivo cellular Pharmacokinetic (PK) profile of HY004 in units of transgene copy number per genomic DNA (gDNA) amount.	To characterize the in vivo cellular pharmacokinetic (PK) profile (levels, persistence, trafficking) of HY004 cells in target tissues (blood, bone marrow andCerebral Spinal Fluid (CSF)if available)by quantitative polymerase chain reaction(qPCR).	Up to 3 months(BM sample); Up to 2 years(Blood sample)
Other	In vivo cellular Pharmacokinetic (PK) profile of HY004 in units of percent of CAR-positive cells.	To characterize the in vivo cellular pharmacokinetic (PK) profile (levels, persistence, trafficking) of HY004 cells in target tissues (blood, bone marrow andCerebral Spinal Fluid (CSF)if available)by Flow Cytometry.	Up to 3 months(BM sample); Up to 2 years(Blood sample)
Other	In vivo cellular pharmacodynamics (PD) profile of HY004.	To characterize the concentration of cytokines ,including Interleukin-6(IL-6) at least in Serum.	28 days
Other	Prevalence and incidence of humoral immunogenicity to HY004.	To characterize the concentration of anti-drug antibodies.	2 years
Primary	Overall Remission Rate (ORR)	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).	at the end of Month 3
Secondary	Overall Remission Rate (ORR)	ORR is defined as Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi) per NCCN classification.	within 3 months
Secondary	Best overall response (BOR)	The proportion of patients who have achieved the best response (CR or CRi) after HY004 treatment.	up to 2 years
Secondary	Overall Remission Rate (ORR) with minimal residual disease (MRD) negativity	Overall Remission Rate (ORR) with minimal residual disease (MRD) negativity as determined by IRC and Investigators; MRD negativity as determined using flow cytometry.	at the end of Month 3
Secondary	Duration of remission (DOR)	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.	to data cutoff date
Secondary	Allogeneic Stem Cell Transplant (Allo-SCT) rate	The proportion of patients who have received Allo-SCT after HY004 treatment.	First infusion date of HY004 to data cutoff date(up to 2 years)
Secondary	Relapse Free Survival (RFS)	RFS is defined as the time from the HY004 infusion date to the date of disease relapse or death from any cause.	up to 2 years
Secondary	Event-Free Survival(EFS)	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.	up to 2 years
Secondary	Overall survival (OS)	OS is defined as the time from the HY004 Cell Injection infusion to the date of death from any cause.	2 years
Secondary	Percentage of Participants Experiencing Treatment-Emergent Adverse Events(TEAE)	Evaluate the type, frequency, severity of adverse events, and abnormal laboratory test values; Evaluate the frequency and severity of adverse events related to HY004.	up to 2 years