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

Sponsor

New York Medical College (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04972942

Collaborator

(none)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

A Phase II 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.

Condition or Disease	Intervention/Treatment	Phase
T-cell Acute Lymphoblastic Leukemia T-Cell Acute Lymphoblastic Lymphoma	Drug: Daratumumab	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II 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)

Anticipated Study Start Date :

Sep 1, 2021

Anticipated Primary Completion Date :

Sep 1, 2025

Anticipated Study Completion Date :

Sep 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Other: Interventional Daratumumab (DARA) treatment post-HCT 8 mg/kg/dose Induction: DARA 16 mg/kg IV weekly x 8 doses (Weeks 1-8) Consolidation: DARA 16 mg/kg IV every 2 weeks x 8 doses (Weeks 9-24) Maintenance: DARA 16 mg/kg IV every 4 weeks x 5 doses following start of treatment (Weeks 25-44)	Drug: Daratumumab Total body irradiation (TBI)-based myeloablative allogeneic hematopoietic stem cell transplantation (HCT) using best available donor. Daratumumab (DARA) treatment post-HCT Induction: DARA 16 mg/kg IV weekly x 8 doses (Weeks 1-8) Consolidation: DARA 16 mg/kg IV every 2 weeks x 8 doses (Weeks 9-24) Maintenance: DARA 16 mg/kg IV every 4 weeks x 5 doses following start of treatment (Weeks 25-44) Other Names: Darzalex®

Arm

Intervention/Treatment

Other: Interventional

Daratumumab (DARA) treatment post-HCT 8 mg/kg/dose Induction: DARA 16 mg/kg IV weekly x 8 doses (Weeks 1-8) Consolidation: DARA 16 mg/kg IV every 2 weeks x 8 doses (Weeks 9-24) Maintenance: DARA 16 mg/kg IV every 4 weeks x 5 doses following start of treatment (Weeks 25-44)

Drug: Daratumumab

Total body irradiation (TBI)-based myeloablative allogeneic hematopoietic stem cell transplantation (HCT) using best available donor. Daratumumab (DARA) treatment post-HCT Induction: DARA 16 mg/kg IV weekly x 8 doses (Weeks 1-8) Consolidation: DARA 16 mg/kg IV every 2 weeks x 8 doses (Weeks 9-24) Maintenance: DARA 16 mg/kg IV every 4 weeks x 5 doses following start of treatment (Weeks 25-44)

Other Names:

Darzalex®

Outcome Measures

Primary Outcome Measures

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

Relapse free survival [1 year]
To measure relapse free survival in patients post HCT and daratumumab

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 39 Years

Sexes Eligible for Study:

All

Accepts 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
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