Phase I Trial of Targeted Immunotherapy With Daratumumab Following Myeloablative TBI-Based Conditioning and AlloHCT in Children, Adolescents and Young Adults With High Risk T-Cell Acute Lymphoblastic Leukemia and Lymphoma (ALLO-T-DART)

Summary

A Phase I trial to determine the safety of targeted immunotherapy with daratumumab (DARA) IV after total body irradiation (TBI)-based myeloablative conditioning and allogeneic hematopoietic cell transplantation (HCT) for children, adolescents, and young adults (CAYA) with high risk T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LLy). Pre- and post-HCT NGS-MRD studies will be correlated with outcomes in children, adolescents, and young adults with T-ALL undergoing allogeneic HCT and post-HCT DARA treatment. The study will also evaluate T-cell repertoire and immune reconstitution prior to and following DARA post-HCT treatment and correlate with patient outcomes.

Detailed description

Total body irradiation (TBI)-based myeloablative allogeneic hematopoietic stem cell transplantation (HCT) using best available donor. Daratumumab (DARA) treatment post-HCT: Phase 1: 3 dose levels to determine safety (15 patients) Dose expansion cohort (DEC): Further evaluation of PK and PD (correlative studies/exploratory endpoints) to guide future selection of RP2D (15 patients) Treatment Schedule: 1. Induction: DARA IV weekly x 8 doses (Weeks 1-8) 2. Consolidation: DARA IV every 2 weeks x 8 doses (Weeks 9-24) 3. Maintenance: DARA IV every 4 weeks (Stop at Day +270)

Arms & interventions

• DrugDaratumumab

  Total body irradiation (TBI)-based myeloablative allogeneic hematopoietic stem cell transplantation (HCT) using best available donor. Daratumumab (DARA) treatment post-HCT Phase 1: 3 dose levels to determine safety (15 patients) Dose expansion: 1. Induction: DARA IV weekly x 8 doses (Weeks 1-8) 2. Consolidation: DARA every 2 weeks x 8 doses (Weeks 9-24) 3. Maintenance: DARA every 4 weeks (Stop at Day +270)

Outcome measures

Eligibility criteria