NCT06253637

Daratumumab in VHR T-ALL Treated According to the ALL National Treatment Program

Daratumumab in Very High-Risk T-Lineage Acute Lymphoblastic Leukemia (ALL) Treated According to the ALL National Treatment Program (DARATALL-VHR)

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 31 (estimated)
• Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to test daratumumab in adult very high risk T-lineage lymphoblastic leukemia. The main question it aims to answer is wether the addition of daratumumab daratumumab to the national standard of care is able to increase the rate of MRD-negative patients after induction therapy. Participants will be treated with: • daratumumab in combination with a pediatric-inspired treatment scheme - as in the previous GIMEMA LAL1913 protocol.

Detailed description

This study is a multicenter phase II trial based on the addition of daratumumab to chemotherapy in the front-line treatment of very high-risk T-ALL. T-ALL patients are eligible at diagnosis in case of ETP or near ETP immunophenotype. Due to their biological and clinical similarities, T-Myeloid MPAL can also be included. Other VHR T-ALL patients (i.e. those with WBC count \>100 x109/L, with complex karyotype with ≥5 unrelated anomalies or with a CD1a-negative immunophenotype) will also be eligible. A safety run-in is foreseen for 5 patients: if grade \>3 infusion-related reactions or extra hematologic adverse events of grade \>3 that, for investigator's clinical judgement cannot be due to chemotherapy alone, are not observed in more than 2 patients during the first cycle of daratumumab, the study will continue with the core phase. After a steroid/cyclophosphamide pre-treatment phase, that can occur before enrollment during the screening period, patients who meet the eligibility criteria will be treated with daratumumab in combination with a pediatric-inspired treatment scheme - as in the previous GIMEMA LAL1913 protocol.

Conditions

• T-Lymphocytic Leukemia, Acute

Interventions

Type	Name	Description
DRUG	Daratumumab plus chemotherapy according to the national treatment program	Daratumumab is a human IgG1қ monoclonal antibody that binds with high affinity to a unique epitope on CD38, a transmembrane glycoprotein which is expressed in several hematological malignancies including multiple myeloma (MM) and ALL. Daratumumab induces lysis of CD38-expressing tumor cells by several mechanisms. Intravenous daratumumab has been approved first as a single agent and then in combinations in the MM setting and in AL amyloidosis. The activity of daratumumab in ALL is being explored in the DELPHINUS trial, in which the drug was combined with chemotherapy in pediatric and young adult patients with relapsed/refractory T-cell ALL or lymphoblastic lymphoma (LL). In the present trial, daratumumab will be administered to adult Very high risk T-lineage ALL weekly in induction and early consolidation (C1-C2), and the first day of each of the following intensive cycles up to C8.

Timeline

• Start date: 2024-10-17
• Primary completion: 2029-10-01
• Completion: 2029-10-01
• First posted: 2024-02-12
• Last updated: 2026-03-05

Locations

3 sites across 1 country: Italy