Sponsor changed product development plan

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).

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.

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.

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.