Use of T-allo10 in Hematopoietic Stem Cell Transplantation (HSCT) for Blood Disorders

NCT03198234 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: IRB-38734PEDSBMT2975P01CA049605-30
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

A significant number of patients with hematologic malignancies need a hematopoietic stem cell transplant (HSCT) to be cured. Only about 50% of these patients have a fully matched donor, the remaining patients will require an HSCT from a mismatched related or unrelated donor. Almost 60% of these mismatched donor HSCTs will result in graft-versus-host disease (GvHD), which can cause significant morbidity and increased non-relapse mortality. GvHD is caused by the donor effector T cells present in the HSC graft that recognize and react against the mismatched patient's tissues. Researchers and physicians at Lucile Packard Children's Hospital, Stanford are working to prevent GvHD after HSCT with a new clinical trial. The objective of this clinical program is to develop a cell therapy to prevent GvHD and induce graft tolerance in patients receiving mismatched unmanipulated donor HSCT. The cell therapy consists of a cell preparation from the same donor of the HSCT (T-allo10) containing T regulatory type 1 (Tr1) cells able to suppress allogenic (host-specific) responses, thus decreasing the incidence of GvHD. This is the first trial of its kind in pediatric patients and is only available at Lucile Packard Children's Hospital, Stanford. The purpose of this phase 1 study is to determine the safety and tolerability of a cell therapy, T-allo10, to prevent GvHD in patients receiving mismatched related or mismatched unrelated unmanipulated donor HSCT for hematologic malignancies.

Conditions

AML - Acute Myeloid Leukemia; MDS (Myelodysplastic Syndrome); Mixed Phenotype Acute Leukemia; NHL - Non-Hodgkin's Lymphoma; Hodgkin's Lymphoma; ALL

Keywords

Pediatric; GvHD; Hematopoietic Stem Cell Transplantation; Stem Cells; Transplant; BMT - bone marrow transplant

Outcome Measures

Primary Outcomes (4)

• Number of Participants Experiencing Treatment Emergent Adverse Events (TEAE)

  Number of participants experiencing TEAEs. Assessments of TEAE will include laboratory abnormalities, changes in vital signs, and changes in physical examination related to the infusion of T-allo10 cells in order to assess the tolerability of T-allo10.

  Time of T-allo10 cell infusion until 28 days following the infusion.

• Severity of Treatment Emergent Adverse Events (TEAE)

  Number of participants experiencing TEAEs related to infusion, by severity graded according to the CTCAE grading system, from grade 1 (least severe) to grade 5 (death). Assessments of TEAE will include laboratory abnormalities, changes in vital signs, and changes in physical examination following infusion of T-allo10 cells in order to assess the safety of T-allo10.

  Time of T-allo10 cell infusion until 28 days following the infusion.

• Number of Participants Who Achieved Stem Cell Engraftment After Hematopoietic Stem Cell Transplant (HSCT).

  Stem cell engraftment is evaluated by clinical laboratory studies including absolute neutrophil count above 500/mm3 for three consecutive days, hematopoiesis at bone marrow examination, with cellularity \>5 % and donor chimerism \>90% by short tandem repeat (STR) analysis for the presence of donor cells, and minimal residual disease (MRD) assay \< 0.1%.

  +42 days post HSCT

• Number of Successful T-allo10 Products Manufactured for Patients Enrolled

  Feasibility defined by the rate of successful manufacture of the T-allo10 product to satisfy the targeted dose level and meet the required release specifications. Number of products meeting specifications out of total products manufactured is reported.

  By Day -2

Secondary Outcomes (1)

• Number of Participants Who Experienced Grade III and/or IV Acute GvHD

  Study visits through Day +100

Other Outcomes (3)

• Number of Patients Who Developed Chronic GvHD

  After Day +100 through Day +365

• Number of Days to Reach Immune Reconstitution

  Up to Day 365

• Number of Participants Who Experienced Disease Free Survival

  At Day +365

Study Arms (3)

Cohort 1

EXPERIMENTAL

Participants will receive 1 X 10\^6/kg (± 10%) T-allo10 cells infused intravenously on Day -1 (day before transplant)

Biological: T-allo10

Cohort 2

EXPERIMENTAL

Participants will receive 3 X 10\^6/kg (± 10%) T-allo10 cells infused intravenously on Day -1 (day before transplant)

Biological: T-allo10

Cohort 3

EXPERIMENTAL

Participants will receive 9 X 10\^6/kg (± 10%) T-allo10 cells infused intravenously on Day -1 (day before transplant)

Biological: T-allo10

Interventions

T-allo10 BIOLOGICAL

The T-allo10 drug product consists of donor derived, host (patient) alloantigen hyporesponsive (anergic) CD4+ (cluster of differentiation 4) cells containing Type 1 regulatory T (Tr1) cells induced in vitro in the presence of IL-10 (interleukin-10), which are also defined as IL-10 anergized T cells. T-allo10 cell infusion is being developed to prevent acute Graft-versus-Host Disease (GvHD) and induce graft tolerance in patients with hematologic malignancies receiving mismatched related and unrelated unmanipulated hematopoietic stem cell transplant (HSCT).

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 3 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Eligible diseases include:
• A. Acute Lymphoblastic Leukemia (B- or T-ALL)
• Complete Response (CR)1-ultra high risk features
• Unfavorable cytogenetics
• Hypodiploidy
• Induction failure
• Minimal Residual Disease (MRD) positive after consolidation
• CR-2:
• Any of the high risk features listed in CR1
• B-ALL: any relapse considered eligible for transplant
• T- ALL
• CR-3-any
• B. Acute Myeloid Leukemia
• MRD \>5% at day 22 induction 1
• MRD \>0.1% after induction 2

You may not qualify if:

• Prior bone marrow or peripheral blood HSCT within the last 6 (six) months
• HLA-matched related or unrelated donor available
• Any active, uncontrolled infection at the time of enrollment
• Pregnant or lactating females
• Any severe concurrent disease which, in the judgement of the investigator, would place the patient at increased risk during participation in the study
• Any subject with a history of significant renal, hepatic, pulmonary, or cardiac dysfunction or on treatment to support cardiac dysfunction
• HIV positive
• Non-cooperative behavior or non-compliance of the patient and/or of his/her family
• Received another investigational agent within 30 days of enrollment
• Patients with Down's syndrome

Sponsors & Collaborators

• Roncarolo, Maria Grazia, MD: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Lucile Packard Children's Hospital

Palo Alto, California, 94304, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Anemia, Refractory, with Excess of Blasts; Leukemia, Biphenotypic, Acute; Lymphoma, Non-Hodgkin; Hodgkin Disease

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia, Refractory; Anemia; Myelodysplastic Syndromes; Bone Marrow Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma

Limitations and Caveats

Early termination led to a small number of participants analyzed.

Results Point of Contact

• Title: Rajni Agarwal, MD
• Organization: Stanford

rajnia@stanford.edu

650-725-9250

Study Officials

• Rajni Agarwal, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics

Study Record Dates

• First Submitted: April 11, 2017
• First Posted: June 26, 2017
• Study Start: August 30, 2017
• Primary Completion: November 11, 2021
• Study Completion: November 11, 2021
• Last Updated: July 18, 2024
• Results First Posted: July 18, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)