Naive T Cell Deplete Grafts for GVHD Prevention in Non-Malignant Diseases

NCT07660783 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 20798RG1126016
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial investigates how well a naive T cell depleted graft work for the reduction of graft versus host disease in patients with non-malignant diseases requiring hematopoietic cell transplantation. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells.

Conditions

Bone Marrow Failure; Hemoglobinopathies; Primary Immune Deficiency (PID); Autoimmune Cytopenia; Immune Dysregulation; Hemophagocytic Lymphohistiocytosis (HLH); Non Malignant Disorders

Outcome Measures

Primary Outcomes (1)

• GVHD-free Survival

  Free of grade III-IV acute and NIH chronic (moderate-severe) GVHD requiring systemic immunosuppression

  1 year post-transplant

Secondary Outcomes (8)

• Overall survival

  1 year post-transplant

• Transplant related mortality

  Day 100 post-transplant and 1 year post-transplant

• Graft failure

  Day 42 post-transplant

• Graft rejection

  Day 100 post-transplant

• Incidence of chronic GVHD

  At 1 year and 2 years post transplant

Study Arms (2)

Arm A (HLA-Haploidentical or mismatched unrelated donor)

OTHER

Conditioning regimen for HLA-Haploidentical or mismatched unrelated donor consisting of Cyclophosphamide (50 mg/kg x1 day), Fludarabine 35 mg/m2/day x 5 days, Thiotepa (5 mg/kg/day x 2 days), TBI (200 cGy x 2). Tacrolimus starting Day -1, MMF D0-35.

Biological: ALLOGENEIC CD34+ ENRICHED AND CD45RA- DEPLETED PBSCs

Arm B (HLA-matched related or matched unrelated donor )

OTHER

Conditioning regimen for HLA-matched related or matched unrelated donor consisting of Cyclophosphamide (50 mg/kg x1 day), Fludarabine (30 mg/m2/day x 5 days), Thiotepa (5 mg/kg/day x 2 days), TBI (200 cGy x 2). Tacrolimus starting Day -1, MMF D0-35.

Biological: ALLOGENEIC CD34+ ENRICHED AND CD45RA- DEPLETED PBSCs

Interventions

ALLOGENEIC CD34+ ENRICHED AND CD45RA- DEPLETED PBSCs BIOLOGICAL

CD34-selected graft with CD45RA- depleted peripheral blood stem cells given to patients with Non-Malignant Diseases

Arm A (HLA-Haploidentical or mismatched unrelated donor); Arm B (HLA-matched related or matched unrelated donor )

Eligibility Criteria

• Age: 6 Months - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Considered appropriate candidate for allogeneic HCT following low dose (4Gy) TBI containing-conditioning and have one of the following diagnoses: A) BMF B)Hemoglobinopathies C)PID D) Autoimmune cytopenias E) Immune dysregulation F) HLH G) Other NMD treatable by HCT and NMD that is not clearly defined (a patient with a NMD for whom genetic testing has been done and a genetic mutation responsible for their NMD phenotype has not been identified) are eligible for the study following discussion with and approval by the protocol PI
• Patients aged 6 months- 5 years old (inclusive) at the time of informed consent
• Recipient informed consent/assent (13 years and older), and/or legal guardian permission must be obtained

You may not qualify if:

• Patient with aplastic anemia
• Patients with severe combined immunodeficiency (SCID)
• Fanconi anemia
• Dyskeratosis congenita
• Patient weight \> 100 kg
• Patients who are positive for HIV-1, HIV-2
• Patients with current neoplastic disorders
• Patients with uncontrolled infections for whom HCT is considered contraindicated by the consulting infectious disease physician.
• Patients with organ dysfunction including A) Renal insufficiency B) Impaired cardiac function C)Impaired pulmonary function D) Liver dysfunction
• Patients who are pregnant or breast-feeding
• Patients on other experimental protocols for prevention of GVHD
• Patients of childbearing age who are presumed to be fertile and are unwilling to use an effective birth control method or refrain from sexual intercourse during and for 12 months post-HCT
• Patients with any other significant medical conditions that would make them unsuitable for transplantation, as determined by the PI
• Patients with a known hypersensitivity to tacrolimus or MMF

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead

Study Sites (2)

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Bone Marrow Failure Disorders; Hemoglobinopathies; Primary Immunodeficiency Diseases; Lymphohistiocytosis, Hemophagocytic

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases

Study Officials

• Madhavi Lakkaraja, MD, MPH

  Fred Hutch Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Madhavi Lakkaraja, MD, MPH

CONTACT

206-667-7166; mlakkara@fredhutch.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: June 16, 2026
• First Posted: June 22, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2031
• Study Completion (Estimated): September 1, 2035
• Last Updated: June 22, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)