Daratumumab in Very High-Risk T-Lineage Acute Lymphoblastic Leukemia (ALL) Treated According to the ALL National Treatment Program (DARATALL-VHR)
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.
• Age 18-65 years.
• A diagnosis of T-ALL according to the 2022 International Consensus Classification (ICC) is required, either de novo or secondary to chemo-radiotherapy for another cancer. Pre-treatment with low-dose corticosteroids +/- cyclophosphamide in patients presenting with hyperleukocytosis is allowed.
• Availability of fresh bone marrow (BM) (or peripheral blood (PB) in patients with hyperleukocytosis) samples to perform diagnostic procedures. ).
• Bone marrow blast percentage at diagnosis ≥20%.
• CD38 positivity on ALL blasts (any level of positivity).
• ETP and near ETP at diagnosis according to internationally accepted criteria (appendix G) at diagnosis or other VHR T-ALL subtypes (WBC count \>100 x109/L; complex karyotype with ≥5 unrelated anomalies; other CD1a-negative immunophenotypes). T-Myeloid MPAL according to the 2022 ICC of Acute Leukemias of Ambiguous Lineage (appendix H) can also be eligible and considered as VHR.
• Availability of full cytological, cytochemical, immunophenotypic, cytogenetic and molecular disease characterization according to the EGIL and WHO classifications.
• An ECOG performance status 0-2, unless a performance of 3 is unequivocally caused by the disease itself, (and not by pre-existing comorbidities,) and is considered and/or documented to be reversible following the application of anti-leukemic therapy and appropriate supportive measures.
• For females of childbearing potential, a negative pregnancy test must be documented. Female and male patients who are fertile must agree to use an effective form of contraception with their sexual partners from enrollment through 12 months after the end of treatment.
⁃ Signed written informed consent according to ICH/E U/GCP and national local laws.