Targeted Immunotherapy After Myeloablative TBI-Based Conditioning & AlloHCT in CAYA With High Risk T-Cell ALL & Lymphoma

Study Overview
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Brief Summary
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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
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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: Induction: DARA IV weekly x 8 doses (Weeks 1-8) Consolidation: DARA IV every 2 weeks x 8 doses (Weeks 9-24) Maintenance: DARA IV every 4 weeks (Stop at Day +270)

Official Title
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Phase I Trial of Targeted Immunotherapy With Daratumumab Following Myeloablative TBI-Based Conditioning and AlloHCT in Children, Adolescents and Young Adults With High Risk T-Cell Acute Lymphoblastic Leukemia and Lymphoma (ALLO-T-DART)

Conditions
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T-cell Acute Lymphoblastic Leukemia, T-Cell Acute Lymphoblastic Lymphoma

Intervention / Treatment
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* Drug: Daratumumab


Participation Criteria
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Eligibility Criteria
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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 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

Ages Eligible for Study
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Maximum Age: 39 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Phase 1: 3 dose levels to determine safety. Followed by dose expansion cohort.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Interventional<br>Phase 1: 3 dose levels to determine safety (15 patients) Dose expansion: Daratumumab (DARA) treatment post-HCT Induction: DARA IV weekly x 8 doses (Weeks 1-8) Consolidation: DARA IV every 2 weeks x 8 doses (Weeks 9-24) Maintenance: DARA IV every 4 weeks (Stop at Day +270) | Drug: Daratumumab<br>* 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: Induction: DARA IV weekly x 8 doses (Weeks 1-8) Consolidation: DARA every 2 weeks x 8 doses (Weeks 9-24) Maintenance: DARA every 4 weeks (Stop at Day +270)<br>* Other names: Darzalex®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients with dose limiting toxicity (per CTCAE v.5) | occurrence of any Grade ≥ 3 non hematologic toxicity (per CTCAE v.5) which is probably, or definitely related to daratumumab | 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse free survival | To measure relapse free survival in patients post HCT and daratumumab | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunotherapy, children, adolescents, young adults