Clinical trial NCT06009107: A Study of HY004 Treatment in Adult Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r 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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: B-cell Acute Lymphoblastic Leukemia
Keywords: HY004
Cluster of differentiation antigen 19 and/or 22(CD19 and/or 22)
CD19/22-directed CAR-T cells
Lead sponsor: Juventas Cell Therapy Ltd.
Sponsor class: INDUSTRY
First posted: 2023-08-24
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Remission Rate (ORR)
timeFrame: at the end of Month 3
Secondary outcomes:
measure: Overall Remission Rate (ORR)
timeFrame: within 3 months
measure: Best overall response (BOR)
timeFrame: up to 2 years
measure: Overall Remission Rate (ORR) with minimal residual disease (MRD) negativity
timeFrame: at the end of Month 3
measure: Duration of remission (DOR)
timeFrame: to data cutoff date
measure: Allogeneic Stem Cell Transplant (Allo-SCT) rate
timeFrame: First infusion date of HY004 to data cutoff date(up to 2 years)
measure: Relapse Free Survival (RFS)
timeFrame: up to 2 years
measure: Event-Free Survival(EFS)
timeFrame: up to 2 years
measure: Overall survival (OS)
timeFrame: 2 years
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events（TEAE）
timeFrame: up to 2 years
Other outcomes:
measure: In vivo cellular Pharmacokinetic (PK) profile of HY004 in units of transgene copy number per genomic DNA (gDNA) amount.
timeFrame: Up to 3 months(BM sample); Up to 2 years(Blood sample)
measure: In vivo cellular Pharmacokinetic (PK) profile of HY004 in units of percent of CAR-positive cells.
timeFrame: Up to 3 months(BM sample); Up to 2 years(Blood sample)
measure: In vivo cellular pharmacodynamics (PD) profile of HY004.
timeFrame: 28 days
measure: Prevalence and incidence of humoral immunogenicity to HY004.
timeFrame: 2 years
Locations:
Study officials:
affiliation: Study Principal Investigator Institute of Hematology & Blood Diseases Hospital
name: Jianxiang Wang M.D.
role: PRINCIPAL_INVESTIGATOR
References: