Targeted Immunotherapy After Myeloablative TBI-Based Conditioning & AlloHCT in CAYA with High Risk T-Cell ALL & Lymphoma
Purpose
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.
Conditions
- T-cell Acute Lymphoblastic Leukemia
- T-Cell Acute Lymphoblastic Lymphoma
Eligibility
- Eligible Ages
- Under 39 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Sequential Assignment
- Intervention Model Description
- Phase 1: 3 dose levels to determine safety. Followed by dose expansion cohort.
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Other Interventional |
Phase 1: 3 dose levels to determine safety (15 patients) Dose expansion: Daratumumab (DARA) treatment post-HCT 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) |
|
Recruiting Locations
Loma Linda, California 92354
Gainsville, Florida 32608
Indianapolis, Indiana 46202
Grand Rapids, Michigan 49503
Vallhala, New York 10595
Philadelphia, Pennsylvania 19104
More Details
- NCT ID
- NCT04972942
- Status
- Recruiting
- Sponsor
- New York Medical College
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)