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 Sex
- 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 5367696, California 5332921 92354
Gainsville, Florida 4155751 32608
Indianapolis 4259418, Indiana 4921868 46202
Grand Rapids 4994358, Michigan 5001836 49503
Vallhala, New York 5128638 10595
Philadelphia 4560349, Pennsylvania 6254927 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)