ClinicalTrials.gov record NCT07660783
Naive T Cell Deplete Grafts for GVHD Prevention in Non-Malignant Diseases
A Phase II Prospective Study Evaluating Selective Depletion of CD45RA+ (Naïve) T Cells (TND) From Peripheral Blood Stem Cell (PBSC) Grafts for Prevention of Graft Versus Host Disease (GVHD) in Non-Malignant Diseases (NMDs)
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AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This Phase II interventional study tests donor peripheral blood stem cell grafts that have had naïve (CD45RA+) T cells removed in people with various non-malignant disorders who need a hematopoietic cell transplant. Participants receive a specified conditioning regimen including chemotherapy and low‑dose total‑body irradiation, the CD34+ enriched/CD45RA‑depleted graft, and GVHD prophylaxis with tacrolimus and mycophenolate mofetil, then are followed for up to two years. The main outcome measured is GVHD‑free survival at 1 year.
What it is studying. The study is testing whether transplanting donor PBSC grafts that are enriched for CD34+ cells and depleted of CD45RA+ (naïve) T cells, given after a defined conditioning regimen and with tacrolimus/MMF prophylaxis, affects graft‑versus‑host disease and related transplant outcomes. The primary outcome is GVHD‑free survival at 1 year; secondary outcomes include overall survival, transplant‑related mortality, graft failure or rejection, chronic GVHD, infections, and donor chimerism.
What the researchers hope to learn. Scientific goals: measure GVHD‑free survival at 1 year (free of grade III‑IV acute and moderate‑severe chronic GVHD requiring systemic immunosuppression); assess overall survival; assess transplant‑related mortality; measure graft failure and graft rejection rates; track incidence and severity of chronic GVHD; document systemic steroid use for GVHD; record opportunistic viral infections in the first year; and report donor peripheral blood chimerism up to 2 years.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
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.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Biological
- ALLOGENEIC CD34+ ENRICHED AND CD45RA- DEPLETED PBSCs
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- 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
- Patient with suitable HCT donor (see inclusion criteria below)
- Recipient informed consent/assent (13 years and older), and/or legal guardian permission must be obtained
Exclusion criteria
- 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
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Detailed description from the registry
OUTLINE: Patients will receive CD34+ enriched CD45RA-depleted donor T-lymphocytes IV on day 0. For conditioning, patients receive cyclophosphamide by IV on day -8, fludarabine by IV on day -7 to day -3, thiotepa IV on day -7 and day -6, and undergo total-body irradiation (TBI) for 2 doses on day -2 and day -1. GVHD Prophylaxis: All patients also receive tacrolimus IV continuously starting on day -1, and mycophenolate mofetil (MMF) starting day 0 through day 35. If there is no evidence of grade II-IV acute GVHD on or prior to day 100, tacrolimus is tapered. All patients also undergo bone marrow aspiration/biopsy and collection of blood samples throughout the trial. After completion of study treatment, patients are followed up at days 7, 14, 21, 28, 56, 80, 180, and 270 and at 1, 1.5, and 2 years.
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AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Participants receive a conditioning course of chemotherapy (cyclophosphamide, fludarabine, thiotepa) and two doses of total-body irradiation, then an IV infusion on day 0 of a donor peripheral blood stem-cell graft that is CD34+ enriched and CD45RA (naïve T cell)-depleted. GVHD prophylaxis with tacrolimus (IV starting day −1) and mycophenolate mofetil (day 0–35) is given per protocol. Patients will have blood samples collected and undergo bone marrow aspiration/biopsy at multiple times during the trial. After treatment they are followed at days 7, 14, 21, 28, 56, 80, 180, and 270 and at 1, 1.5, and 2 years for ongoing assessments.
How the study is structured. Phase II, interventional (treatment) study that is non-randomized and has two parallel arms defined by donor type (haploidentical or mismatched unrelated donor versus matched related or matched unrelated donor). There is no masking. All participants receive a conditioning regimen (cyclophosphamide, fludarabine, thiotepa, low‑dose TBI), an allogeneic CD34+ enriched and CD45RA‑depleted PBSC graft, and GVHD prophylaxis with tacrolimus and mycophenolate mofetil, with scheduled follow-up visits through 2 years.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- The registry says recruitment has not started. When is it expected to open, and can I register interest now?
- The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on hemophagocytic lymphohistiocytosis
Important dates
- Study start
- September 2026 (estimated)
- Primary completion
- September 2031 (estimated)
- Study completion
- September 2035 (estimated)
- Target enrollment
- 40 participants (estimated)
- Last updated on registry
- Jun 22, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Fred Hutchinson Cancer Center
- Principal investigator
- Madhavi Lakkaraja, Assistant Professor
Fred Hutchinson Cancer Center
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Madhavi Lakkaraja, MD, MPH 📞 206-667-7166 ✉ mlakkara@fredhutch.org
Participating sites (2)
- Seattle Children's Hospital
Seattle, Washington, 98105 · United States
- Fred Hutchinson Cancer Center
Seattle, Washington, 98109 · United States
Terms used on this page · explanations by MedicalUpdates.ai
- stem cell transplant
- A procedure that replaces blood-forming cells after high-dose treatment. 'Autologous' uses the person's own cells collected beforehand; 'allogeneic' uses cells from a donor.
- informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- inclusion criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- assent
- A child's or dependent adult's agreement to take part, given alongside the formal consent of a parent or legal representative.
- legal guardian
- A person who is legally allowed to make decisions, including consent to research, on behalf of someone who cannot consent for themselves.
- contraindicated
- A reason a particular test or treatment should not be used for a person, for example a metal implant that rules out an MRI scan.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- biopsy
- Removal of a small piece of tissue so it can be examined under a microscope. 'Biopsy-proven' or 'histologically confirmed' means the diagnosis was confirmed by examining tissue under a microscope.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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