Clinical Study of Recombinant Anti-CD19m-CD3 Antibody Injection (A-319)
ConditionAcute Lymphocytic Leukemia
Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-75
SponsorShanxi Bethune Hospital
About this trial
This is an exploratory study with an open-label, single-arm, single-center design. It plans to enroll subjects with refractory/relapsed acute B-cell lymphoblastic leukemia (B-ALL), or treatment-naive or previously treated B-ALL subjects who achieved complete remission (CR) after induction chemotherapy but still have positive minimal residual disease (MRD). The primary objectives are to preliminarily evaluate the safety, tolerability, pharmacokinetics, biology, preliminary efficacy, and immunogenicity of A-319 subcutaneous injection.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
1.Aged 18 to 75 years (inclusive), regardless of gender;
2.Confirmed diagnosis of refractory or relapsed acute B-cell lymphoblastic leukemia (B-ALL) with positive CD19 expression. Definition of refractory or relapsed: failure to respond to conventional induction chemotherapy; early relapse (relapse within 12 months of first remission); relapse after 12 months of first remission with failure to achieve remission following re-induction with the original regimen; second or subsequent relapse, relapse after autologous hematopoietic stem cell transplantation (Auto-HSCT), or relapse after allogeneic hematopoietic stem cell transplantation (Allo-HSCT). (For patients with Philadelphia chromosome-positive [Ph+] disease, they must have received treatment with at least one tyrosine kinase inhibitor [TKI].);
3.Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2;
4.Bone marrow blast percentage of at least 5% (determined by morphology);
Disqualifiers
1.Central nervous system (CNS) leukemia (confirmed by cerebrospinal fluid [CSF] analysis) or acute lymphoblastic leukemia (ALL) with clinically relevant CNS involvement;
2.Burkitt's leukemia, testicular infiltration in acute lymphoblastic leukemia (ALL);
3.A history of malignancy other than ALL within 5 years prior to the initiation of protocol-specific treatment. Exceptions include: malignancies treated with curative intent, with no known active disease for 5 years before enrollment, and deemed by the treating physician to have a low recurrence risk; non-melanoma skin cancer or lentigo maligna that has been adequately treated with no evidence of recurrence; carcinoma in situ of the cervix that has been adequately treated with no evidence of recurrence; ductal carcinoma in situ of the breast that has been adequately treated with no evidence of recurrence;and prostatic intraepithelial neoplasia with no evidence of prostate cancer;
4.Patients with grade 2-4 acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (Allo-HSCT), or those with chronic GVHD requiring immunosuppressive therapy;
Trial design
Design model
Sequential
Treatments tested in this trial
Treatment with A319
DrugThe maximum duration of treatment is no more than 4 cycles (one cycle is defined as: 1 week of induction + 3 weeks of treatment + 2 weeks of drug withdrawal). During the 1st week, induction doses of 0.15 μg/kg, 0.45 μg/kg, and 0.9 μg/kg will be administered subcutaneously on Days 1, 3, and 5 respectively. From Weeks 2 to 4, the corresponding treatment dose will be administered subcutaneously on Days 1, 3, and 5 of each week. Weeks 5 to 6 will be the drug withdrawal period.
Treatment groups
18 Participants
are divided into 3 treatment groupsGroup A: 1.8 μg/kg dose groupExperimental treatment 1 intervention
Group B: 3.6 μg/kg dose groupExperimental treatment 1 intervention
Group C: 5.0 μg/kg dose groupExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Safety Analysis
Safety will be evaluated based on the incidence and severity of adverse events (AEs) and serious adverse events (SAEs).
Time frame
From the signing of the informed consent form to 30 days after the last dose2
Characteristics of Dose-Limiting Toxicity (DLT)
Dose Limiting Toxicity (DLT) is defined as the occurrence of Grade 3 or higher non-hematologic toxicity (including neurotoxicity) during the first cycle (4 weeks of treatment plus 2 weeks of treatment holiday).
Time frame
During the first cycle (each cycle lasts 42 days)Secondary outcomes
1
Peripheral Blood Lymphocyte Count
Pharmacodynamic endpoints:Detection of CD20+, CD19+, CD3+ T cells, CD4+ T cells, and CD8+ T cells.
Time frame
No more than 4 cycles (each cycle is 42 days)2
Maximum Concentration (Cmax)
Pharmacokinetic endpoints
Time frame
During the first cycle (each cycle lasts 42 days)3
Mean
It will be evaluated based on the levels of cytokines (IL-2, IL-4, IL-6, IL-8, IL-10, IFNγ, TNFα, IL-1β) in peripheral blood.
Time frame
During the first cycle (each cycle lasts 42 days)4
Best response rate
Hematologic Complete Remission (CR) or Hematologic Complete Remission with Incomplete Hematologic Recovery (CRi)
Time frame
No more than 4 cycles (each cycle is 42 days)Locations
Sponsors and contacts
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Source ClinicalTrials.gov
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