B-cell Acute Lymphoblastic Leukemia
Conditions
Keywords
HY004, Cluster of differentiation antigen 19 and/or 22(CD19 and/or 22), CD19/22-directed CAR-T cells
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.
Interventions
DRUGCyclophosphamide
Administered intravenously.
DRUGFludarabine Phosphate
Administered intravenously.
BIOLOGICALHY004
A single infusion of Autologous 2nd generation CD19/CD22-directed CAR-T cells administered intravenously.
Sponsors
Juventas Cell Therapy Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Best overall response (BOR) | up to 2 years | The proportion of patients who have achieved the best response (CR or CRi) after HY004 treatment. |
| 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. |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| In vivo cellular Pharmacokinetic (PK) profile of HY004 in units of percent of CAR-positive cells. | Up to 3 months(BM sample); Up to 2 years(Blood sample) | 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. |
| In vivo cellular pharmacodynamics (PD) profile of HY004. | 28 days | To characterize the concentration of cytokines ,including Interleukin-6(IL-6) at least in Serum. |
| Prevalence and incidence of humoral immunogenicity to HY004. | 2 years | To characterize the concentration of anti-drug antibodies. |
| In vivo cellular Pharmacokinetic (PK) profile of HY004 in units of transgene copy number per genomic DNA (gDNA) amount. | Up to 3 months(BM sample); Up to 2 years(Blood sample) | 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). |
Outcome results
None listed