Clinical trial · Interventional
Selective Depletion of CD45RA+T Cells From Allogeneic Peripheral Blood Stem Cell Grafts for the Prevention of GVHD
A Multi-center Phase II Study of Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts for the Prevention of GVHD
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Why stopped (as posted): Did not reach one of the primary endpoints of decreased total acute GVHD
Summary
Brief summary (as posted)
RATIONALE: Allogeneic hematopoietic stem cell transplant (HSCT) is a treatment that can cure acute leukemia and myelodysplasia. After giving the patient chemotherapy and total body irradiation to stop the growth of cancer and remove the patient's diseased bone marrow, healthy stem cells from a donor are infused into the patient to replace the patient's bone marrow and make red and white blood cells and platelets. Unfortunately HSCT is often complicated by 'graft versus host disease' (GVHD) in which the transplanted cells from a donor can make an immune response against the body's normal cells and cause tissue damage and severe symptoms. Removing a subset of the donor T cells, called 'naive T cells', before transplant may reduce the frequency and intensity of GVHD. PURPOSE: This phase II trial will determine whether the removal of the naive T cells from donor cells can decrease the rate and severity of graft-vs-host disease while preserving specific immunity against infections in patients with acute leukemia or advanced myelodysplastic syndromes.
Conditions
Conditions (3)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Graft Versus Host Disease | — | UNRESOLVED | — |
| Leukemia | Leukemia | ONTOLOGY_EXACT | 0.90 |
| Myelodysplastic Syndromes | Myelodysplastic Syndrome | ALIAS | 0.90 |
Interventions
Interventions (8)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Allogeneic Hematopoietic Stem Cell Transplantation | Procedure | — | UNRESOLVED |
| Fludarabine Phosphate | Drug | Fludarabine | ALIAS |
| Magnetic Affinity Cell Sorting | Other | — | UNRESOLVED |
| Peripheral Blood Stem Cell Transplantation | Procedure | — | UNRESOLVED |
| Tacrolimus | Drug | — | UNRESOLVED |
| T Cell-Depleted Hematopoietic Stem Cell Transplantation | Biological | — | UNRESOLVED |
| Thiotepa | Drug | Thiotepa | ALIAS |
| Total-Body Irradiation (TBI) | Radiation | — |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Arm 1
- description
- CONDITIONING: Patients undergo total-body irradiation twice daily on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine IV over 30 minutes on days -6 to -2. TRANSPLANTATION: Patients undergo infusion of CD34+ enriched allogeneic peripheral blood stem cells (PBSC) followed by CD45RA+ T-cell-depleted allogeneic PBSC on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Cohort A: Patients receive tacrolimus IV continuously or orally twice daily beginning on day -1 and continuing until day 50 followed by standard taper in the absence of grade II-IV acute GVHD. Cohort B: Patients receive tacrolimus IV continuously or orally twice daily beginning on day -1 and continuing until day 30 followed by rapid taper in the absence of grade II-IV acute GVHD.
- interventionNames
- Drug: Fludarabine Phosphate
- Drug: Tacrolimus
- Drug: Thiotepa
- Radiation: Total-Body Irradiation (TBI)
- Other: Magnetic Affinity Cell Sorting
- Procedure: Peripheral Blood Stem Cell Transplantation
- Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
- Biological: T Cell-Depleted Hematopoietic Stem Cell Transplantation
Primary outcomes (2)
- measure
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 14 Years
- Maximum age
- 55 Years
Show eligibility criteria text
DISEASE CHARACTERISTICS: * Diagnosis of 1 of the following: * Acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML) in first or subsequent remission * ALL or AML in relapse or primary refractory ALL or AML with a circulating blast count ≤ 10,000/mm\^3 * Refractory anemia with excess blasts (RAEB) (RAEB-1 or RAEB-2) if the patient has received induction chemotherapy within the past 60 days * Appropriate candidate for allogeneic hematopoietic stem cell transplantation (HSCT) * No CNS involvement refractory to intrathecal chemotherapy and/or standard cranial-spinal radiotherapy PATIENT CHARACTERISTICS: * Age 14-55 * Creatinine \< 1.5 mg/dL * Cardiac ejection fraction \> 45% * DLCO corrected \> 60% of predicted * Total bilirubin \< 2 times upper limit of normal (ULN) (unless attributed to Gilbert syndrome) * AST and ALT \< 2 times ULN * Not pregnant or nursing * Fertile patients must use effective contraception during and for 12 months after transplantation * HIV negative * No co-existing disease (other than leukemia or RAEB) that would limit life expectancy to \< 3 months * No uncontrolled infection that, in the opinion of the consulting infectious disease physician, would contraindicate myeloablative HSCT * No other medical condition that would contraindicate HSCT * No known hypersensitivity to tacrolimus PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior HSCT * No concurrent participation in other experimental studies for the prevention of graft-vs-host disease DONOR CHARACTERISTICS: * Genotypic or phenotypic HLA-identical related donor * Able to donate peripheral blood stem cells * Age \> 14 years * Applicable to male patients only: No female donors who have previously given birth to a male child or have had a pregnancy beyond the first trimester miscarriage or termination of pregnancy or nursing * No donors who have received blood transfusions * No CD45 Mutation with aberrant CD45RA isoform expression
References
Publications (2)
- DERIVEDBleakley M, Sehgal A, Seropian S, Biernacki MA, Krakow EF, Dahlberg A, Persinger H, Hilzinger B, Martin PJ, Carpenter PA, Flowers ME, Voutsinas J, Gooley TA, Loeb K, Wood BL, Heimfeld S, Riddell SR, Shlomchik WD. Naive T-Cell Depletion to Prevent Chronic Graft-Versus-Host Disease. J Clin Oncol. 2022 Apr 10;40(11):1174-1185. doi: 10.1200/JCO.21.01755. Epub 2022 Jan 10. PMID 35007144
- DERIVEDBleakley M, Heimfeld S, Loeb KR, Jones LA, Chaney C, Seropian S, Gooley TA, Sommermeyer F, Riddell SR, Shlomchik WD. Outcomes of acute leukemia patients transplanted with naive T cell-depleted stem cell grafts. J Clin Invest. 2015 Jul 1;125(7):2677-89. doi: 10.1172/JCI81229. Epub 2015 Jun 8. PMID 26053664