Daratumumab for T Cell ALL With MRD-positive After Standard Chemotherapy

Sponsor
Institute of Hematology & Blood Diseases Hospital, China
Study ID
NCT06570915
Phase
PHASE2
Status
Withdrawn

Conditions

  • ALL, Adult

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Daratumumab Injection — DRUG
    Daratumumab was administered once a week at a dose of 16 mg/kg for a total of 4 times (Day1,8,15,22 ) in one cycle.

Study Details

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.

Key Dates

Start date
Dec 1, 2025
Status verified
May 2026
Primary completion
Sep 1, 2027
Completion
Sep 1, 2028

Study Design

Enrollment
0 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Daratumumab
    Daratumumab was administered once a week at a dose of 16 mg/kg for a total of 4 times (Day1,8,15,22 dosing patterns) in one cycle. Patients with conditions may use up to two cycles of treatment.

Primary Outcome Measure

Rate of conversion from MRD+to MRD- by flow cytometry after 1 cycle of daretuzumab treatment [ Time Frame: up to 28days ±3days after daretuzumab treatment ]

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