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

Conditions

• T-Lymphocytic Leukemia, Acute

Eligibility Criteria

Sex

ALL

Age

18 Years - 65 Years

Healthy Volunteers

Not accepted

Interventions

• Daratumumab plus chemotherapy according to the national treatment program — DRUG
  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.

Study Details

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.

Key Dates

Start date

Oct 17, 2024

Status verified

Mar 2026

Primary completion

Oct 31, 2029

Completion

Oct 31, 2029

Study Design

Enrollment

31 participants (estimated)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Very high risk T-ALL patients treated with daratumumab and the national treatment program
  After a steroid/cyclophosphamide pre-treatment phase, patients will be treated according to the national treatmetn program - as per the previous GIMEMA LAL1913 - plus daratumumab as follows: * In the first cycle, C1, daratumumab (subcutaneous) 1800 mg will be administered on days 1, 8, 15 and 22 * In the second cycle, C2, daratumumab 1800 mg will be administered on days 1, 8, 15 * In the subsequent cycles C3-C8 daratumumab 1800 mg will be administered on day 1 in addition to chemotherapy according to the national treatment program Induction/consolidation cycles are administered at 28 (C1-2) and 21(C2-8) day intervals. Dose reductions are required in patients \> 55y All patients are eligible for allo-SCT after C3. All patients unable to undergo an allo-SCT are eligible for an auto-SCT after C8, If unable to undergo an auto-SCT, these patients are eligible to maintenance at the end of the consolidation program.

Primary Outcome Measure

MRD-negativity rate after cycle 1 [ Time Frame: 1 month ]