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

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)

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).

Study Overview

• Status: Not yet recruiting
• Conditions: B-cell Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Cyclophosphamide; Biological: HY004; Drug: Fludarabine Phosphate

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 Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: JunYin Yu PM; Phone Number: +86-010-65960098; Email: yujunyin@juventas.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Participant Group; 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).

Drug: Cyclophosphamide; Administered intravenously.; Biological: HY004; A single infusion of Autologous 2nd generation CD19/CD22-directed CAR-T cells administered intravenously.; Drug: Fludarabine Phosphate; Administered intravenously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Best overall response (BOR)	The proportion of patients who have achieved the best response (CR or CRi) after HY004 treatment.	up to 2 years
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
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
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)
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
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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
Prevalence and incidence of humoral immunogenicity to HY004.	To characterize the concentration of anti-drug antibodies.	2 years

Collaborators and Investigators

• Sponsor: Juventas Cell Therapy Ltd.
• Investigators: Principal Investigator: Jianxiang Wang M.D., Study Principal Investigator Institute of Hematology & Blood Diseases Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 31, 2024
• Primary Completion (Estimated): December 30, 2024
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: August 18, 2023
• First Submitted That Met QC Criteria: August 18, 2023
• First Posted (Actual): August 24, 2023

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: HY004; Cluster of differentiation antigen 19 and/or 22(CD19 and/or 22); CD19/22-directed CAR-T cells
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine; Fludarabine phosphate
• Other Study ID Numbers: HY004101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Currently the investigators have no plan of interim anaylsis, the investigators don't plan to share individual participant data(IPD) during the trial on-going.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No