Targeted Immunotherapy After Myeloablative TBI-Based Conditioning & AlloHCT in CAYA with High Risk T-Cell ALL & Lymphoma
- Conditions
- T-cell Acute Lymphoblastic LeukemiaT-Cell Acute Lymphoblastic Lymphoma
- Interventions
- Registration Number
- NCT04972942
- Lead Sponsor
- New York Medical College
- Brief 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)
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 30
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Interventional Daratumumab 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)
- Primary Outcome Measures
Name Time Method Patients with dose limiting toxicity (per CTCAE v.5) 60 days occurrence of any Grade ≥ 3 non hematologic toxicity (per CTCAE v.5) which is probably, or definitely related to daratumumab
- Secondary Outcome Measures
Name Time Method Relapse free survival 1 year To measure relapse free survival in patients post HCT and daratumumab
Trial Locations
- Locations (15)
Phoenix Children's Hospital
🇺🇸Phoeniz, Arizona, United States
Loma Linda University Children's Hospital
🇺🇸Loma Linda, California, United States
University of California
🇺🇸San Francisco, California, United States
Children's Hospital Colordao
🇺🇸Aurora, Colorado, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
University of Florida
🇺🇸Gainsville, Florida, United States
John Hopkins All Children's Hospital
🇺🇸St. Petersburg, Florida, United States
Riley Children's Hospital
🇺🇸Indianapolis, Indiana, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Helen DeVos Children's Hospital
🇺🇸Grand Rapids, Michigan, United States
Nationwide Children's Hosptial
🇺🇸Columbus, Ohio, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
New York Medical College
🇺🇸Vallhala, New York, United States