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)
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 (including secondary malignancy)
* 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
