Targeted Immunotherapy After Myeloablative TBI-Based Conditioning & AlloHCT in CAYA with High Risk T-Cell ALL & Lymphoma (ALLO-T-DART)

New York Medical College

Status and phase: Enrolling; Phase 1

Conditions: T-cell Acute Lymphoblastic Leukemia; T-Cell Acute Lymphoblastic Lymphoma

Treatments: Drug: Daratumumab

Study type: Interventional

Funder types: Other

Identifiers

NCT04972942

NYMC-598

Details and patient eligibility

About

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.

Full 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)

Enrollment: 30 estimated patients

Sex: All

Ages: Under 39 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

---

30 participants in 1 patient group

Interventional

Other group

Description:

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)

Treatment:

Drug: Daratumumab