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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: T-cell Acute Lymphoblastic Leukemia; T-Cell Acute Lymphoblastic Lymphoma
• Intervention / Treatment: Drug: Daratumumab

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)

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lauren Harrison, RN, MSN; Phone Number: 6172857844; Email: lauren_harrison@nymc.edu
• Study Contact Backup: Name: Erin Morris, RN; Phone Number: 7149645359; Email: erin_morris@nymc.edu

Study Locations

• United States
  • New York
    • Valhalla, New York, United States, 10595
      • Recruiting
      • New York Medical College
      • Contact: Mitchell Cairo, MD; Phone Number: 914-594-3650; Email: mitchell_cairo@nymc.edu
      • Contact: Lauren Harrison, MSN; Phone Number: 617-285-7844; Email: lauren_harrison@nymc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 39 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Interventional; 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; 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); Other Names: Darzalex®

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: New York Medical College
• Investigators: Study Chair: Mitchell Cairo, MD, New York Medical College; Study Chair: Troy Quigg, DO, Helen DeVos Children's Hospital; Study Chair: Allyson Flower, MD, Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2023
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: July 13, 2021
• First Submitted That Met QC Criteria: July 13, 2021
• First Posted (Actual): July 22, 2021

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 29, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: immunotherapy; children; adolescents; young adults
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Antineoplastic Agents; Daratumumab
• Other Study ID Numbers: NYMC-598

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No