Clinical trial NCT06570915: Daratumumab for T Cell ALL With MRD-positive After Standard Chemotherapy
Official title: A Prospective, Single-arm, Multicenter, Open-label , Phase 2 Study to Evaluate Efficacy and Safety of the Daratumumab in T Cell Acute Lymphoblastic Leukemia With Minimal Residual-Positive After Standard Chemotherapy
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: ALL, Adult
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2024-08-26
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: Daratumumab is administered once a week at a dose of 16 mg/kg for a total of 4 times (Day1,8,15,22) in one cycle. Conditions patients can use up to two cycles of treatment.

Eligibility criteria: Inclusion Criteria:

1. Patients with newly diagnosed T-cell acute lymphoblastic leukemia confirmed by cell morphology and immunophenotype had flow MRD≥0.01% 3 months after chemotherapy; or patients with T-cell acute lymphoblastic leukemia relapsed achieved CR again after salvage chemotherapy, but the flow MRD was ≥0.01%
2. Age ≥18 years old, male or female
3. The expression of CD38 in tumor cells was positive
4. Men and women who may give birth agree to and use effective contraceptive methods
5. Main organ function assessment criteria: total bilirubin \< 1.5× upper normal limit (ULN), glutamic oxalic aminotransferase (AST) and glutamic alanine aminotransferase (ALT) ≤2.5×ULN; Serum creatinine \< 2×ULN; Myocardial enzyme \< 2×ULN; Serum amylase ≤1.5×ULN; Left ventricular ejection fraction (LEF) was \> 45%
6. Understand and sign the informed consent and agree to comply with the study requirements

Exclusion Criteria:

1. SAEs related to the study emerged during the study, and the investigator judged that the necessity of quitting the project was greater than the benefit
2. In case of any situation in which the subjects could not tolerate the study regimen, the investigator assessed that the necessity of withdrawal from the regimen outweighed the benefit
3. The subject had an allergic reaction to any drug of the study regimen or other conditions that prevented the regimen from continuing
4. Subjects voluntarily asked to withdraw from the study at any time
5. Any situation in which the investigator determines that the benefit of withdrawing from the study outweighs the benefit

Primary outcomes:
measure: Rate of conversion from MRD+to MRD- by flow cytometry after 1 cycle of daretuzumab treatment
timeFrame: up to 28days ±3days after daretuzumab treatment
Secondary outcomes:
measure: overall survival overall survival overall survival
timeFrame: up to 2 years after the date of the last enrolled participants
measure: Disease-free survival (DFS)
timeFrame: up to 2 years after the date of the last enrolled participants
measure: Cumulative incidence of relapse (CIR)
timeFrame: up to 2 years after the date of the last enrolled participants
measure: duration of MRD-negative response
timeFrame: up to 2 years after the date of the last enrolled participants
measure: Rate of conversion from MRD+to MRD- by NGS
timeFrame: up to 2 years after the date of the last enrolled participants
measure: 30-day mortality
timeFrame: Within 30 days of the date of the last enrolled participants
measure: 60-day mortality
timeFrame: Within 60 days of the date of the last enrolled participants
Other outcomes:
Locations:
Study officials:
affiliation: Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
name: Hui Wei, doctor
role: PRINCIPAL_INVESTIGATOR
References: