Daratumumab for T Cell ALL With MRD-positive After Standard Chemotherapy
NCT Number: NCT06570915
Acronym: T-ALL-2024
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: ALL, Adult
Interventions: DRUG: Daratumumab Injection
Sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 20
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09-01
Completion Date: 2026-09-01

Summary:
T-ALL accounts for about 15%-25% of Ph-negative ALL, and its clinical prognosis is worse than B-ALL. The successful application of immunotherapy has brought revolutionary progress to the treatment of ALL. But progress in the treatment of T-ALL has been relatively slow. Minimal residual disease (MRD) is a strong prognostic indicator for ALL patients. MRD-positive after induction therapy predicts a high risk of relapse. The National Comprehensive Cancer Network (NCCN) considers MRD-positive ALL patients to be at high risk. Research in the B-ALL field has demonstrated that immunotherapy has the potential to further clear MRD, which in turn translates into survival benefits. Daratumumab is a humanized, anti-CD38 IgG1 monoclonal antibody that binds to CD38 expressed by tumor cells. Apoptosis of tumor cells is induced through a variety of immune-related mechanisms such as complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cytophagocytosis (ADCP), and FCγ receptors, which are currently mainly used in the treatment of multiple myeloma. CD38 is highly and stably expressed on the surface of T-ALL cells, and its expression was less influenced by the previous treatment. Preliminary data from the clinical study of daratumumab combined with BFM bone frame prescription for the treatment of recurrent refractory T ALL(NCT03384654) showed that the effectiveness rate (ORR) was 83.3% in children and 60% in young adults. Compared with the previous historical data, the safety and tolerability were significantly improved. For T-ALL patients who relapse after allogeneic transplantation and achieve CR with intense chemotherapy but continue to have MRD-positive flow rate, daratumumab monotherapy can further clear MRD and achieve the purpose of sustaining CR. These studies all demonstrate the potential role of daratumumab in the treatment of T-ALL. Based on the current difficulties in the treatment of T-ALL and existing research data, we plan to conduct a prospective, single-arm, open-label phase II clinical study to explore the efficacy and safety of daratumumab for flow minimal residual disease positive T-ALL after standard chemotherapy.

Primary Outcome Measures: Rate of conversion from MRD+to MRD- by flow cytometry after 1 cycle of daretuzumab treatment, If no abnormal phenotypic leukemia cells were detected by flow cytometry, flow MRD-negative was considered, up to 28days ±3days after daretuzumab treatment
Secondary Outcome Measures: overall survival overall survival overall survival, The interval from the date of enrollment to the date of death or the date of last follow-up, whichever occurred first., up to 2 years after the date of the last enrolled participants|Disease-free survival (DFS), Only for CR patients who chieved CR. The interval from the date of CR1 to relapse, death from any cause or last follow-up., up to 2 years after the date of the last enrolled participants|Cumulative incidence of relapse (CIR), Calculated with the cumulative incidence method, with death in patients who had a complete hematologic response as a competing risk., up to 2 years after the date of the last enrolled participants|duration of MRD-negative response, No blasts were detected by flow cytometry after daretuzumab treatment, up to 2 years after the date of the last enrolled participants|Rate of conversion from MRD+to MRD- by NGS, Next-generation sequencing (NGS) is a high-throughput sequencing methodology and is a process by which small fragments of DNA are sequenced in parallel multiple times, up to 2 years after the date of the last enrolled participants|30-day mortality, Percentage of patients who died within 30 days from enrollment, Within 30 days of the date of the last enrolled participants|60-day mortality, Percentage of patients who died within 60 days from enrollment, Within 60 days of the date of the last enrolled participants