Clinical trial NCT04972942: Targeted Immunotherapy After Myeloablative TBI-Based Conditioning & AlloHCT in CAYA with High Risk T-Cell ALL & Lymphoma
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: T-cell Acute Lymphoblastic Leukemia
T-Cell Acute Lymphoblastic Lymphoma
Keywords: immunotherapy
children
adolescents
young adults
Lead sponsor: New York Medical College
Sponsor class: OTHER
First posted: 2021-07-22
Enrollment: 30
Sex: ALL
Maximum age (years): 39
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Phase 1: 3 dose levels to determine safety. Followed by dose expansion cohort.
Primary purpose: TREATMENT

Brief 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.

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)

Eligibility criteria: 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

Primary outcomes:
measure: Patients with dose limiting toxicity (per CTCAE v.5)
timeFrame: 60 days
Secondary outcomes:
measure: Relapse free survival
timeFrame: 1 year
Other outcomes:
Locations:
city: Phoeniz
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Loma Linda
country: United States
facility: Loma Linda University Children's Hospital
state: California
city: Los Angeles
country: United States
facility: University of California
state: California
city: San Francisco
country: United States
facility: University of California
state: California
city: Aurora
country: United States
facility: Children's Hospital Colordao
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Gainsville
country: United States
facility: University of Florida
state: Florida
city: St. Petersburg
country: United States
facility: John Hopkins All Children's Hospital
state: Florida
city: Indianapolis
country: United States
facility: Riley Children's Hospital
state: Indiana
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital
state: Michigan
city: Vallhala
country: United States
facility: New York Medical College
state: New York
city: Columbus
country: United States
facility: Nationwide Children's Hosptial
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: New York Medical College
name: Mitchell Cairo, MD
role: STUDY_CHAIR
affiliation: Helen DeVos Children's Hospital
name: Troy Quigg, DO
role: STUDY_CHAIR
affiliation: New York Medical College
name: Allyson Flower, MD
role: STUDY_CHAIR
References: