Overview
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.
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:
- Induction: DARA IV weekly x 8 doses (Weeks 1-8)
- Consolidation: DARA IV every 2 weeks x 8 doses (Weeks 9-24)
- Maintenance: DARA IV every 4 weeks (Stop at Day +270)
Eligibility
Inclusion Criteria:
- 0-39yrs
- T-cell ALL in second or subsequent remission (≤ 5% blasts) or relapsed T-cell LLy with complete response after re-induction therapy
- Planned allogeneic stem cell transplantation with donor identified
- Performance status ≥ 60%
- Fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
- Meet organ function requirements
- Signed IRB approved informed consent
Exclusion Criteria:
- May not have had a prior autologous or allogenic stem cell transplant
- May not have uncontrolled, systemic infection at the time of enrollment
- Known allergies, hypersensitivity, or intolerance to mannitol, sorbitol, corticosteroids, monoclonal antibodies or human proteins, or their excipients
- Must not be pregnant or actively breast feeding
- Seropositive for HIV, hepatitis B or hepatitis C
- COPD
- Asthma
- Clinically significant cardiac disease