T-cell Acute Lymphoblastic Leukemia, T-Cell Acute Lymphoblastic Lymphoma
Conditions
Keywords
immunotherapy, children, adolescents, young adults
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)
Interventions
DRUGDaratumumab
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: 1. Induction: DARA IV weekly x 8 doses (Weeks 1-8) 2. Consolidation: DARA every 2 weeks x 8 doses (Weeks 9-24) 3. Maintenance: DARA every 4 weeks (Stop at Day +270)
Sponsors
New York Medical College
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 1: 3 dose levels to determine safety. Followed by dose expansion cohort.
Eligibility
Sex/Gender
ALL
Age
No minimum to 39 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Relapse free survival | 1 year | To measure relapse free survival in patients post HCT and daratumumab |
Countries
United States
Contacts
CONTACTLauren Harrison, RN, MSN
CONTACTErin Morris, RN
STUDY_CHAIRMitchell Cairo, MD
New York Medical College
STUDY_CHAIRTroy Quigg, DO
Helen DeVos Children's Hospital
STUDY_CHAIRAllyson Flower, MD
New York Medical College
Outcome results
None listed