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

T-cell Acute Lymphoblastic Leukemia Clinical Trial

— ALLO-T-DART  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04972942
• Other study ID #: NYMC-598
• Status: Recruiting
• Phase: Phase 1
• Start date: May 22, 2023
• Est. completion date: September 2028

Study information

• Verified date: June 2023
• Source: New York Medical College
• Contact: Lauren Harrison, RN, MSN
• Phone: 6172857844
• Email: lauren_harrison[@]nymc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: September 2028
• Est. primary completion date: September 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 39 Years

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
• T-cell Acute Lymphoblastic Leukemia
• T-Cell Acute Lymphoblastic Lymphoma

Intervention

Drug:
• Daratumumab
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)

Locations

Country	Name	City	State
United States	New York Medical College	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
New York Medical College

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Relapse free survival	To measure relapse free survival in patients post HCT and daratumumab	1 year