A Phase 2 interventional study of Total-Body Irradiation and Thiotepa in Acute Biphenotypic Leukemia, Acute Leukemia and Acute Leukemia of Ambiguous Lineage, sponsored by Fred Hutchinson Cancer Center. Active, not recruiting at 9 sites in United States. Open to participants aged 6 Months to 26 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-25.
Sponsored by Fred Hutchinson Cancer Center · Phase 2, Interventional, and Treatment
This phase II trial studies how well naive T-cell depletion works in preventing chronic graft-versus-host disease in children and young adults with blood cancers undergoing donor stem cell transplant. Sometimes the transplanted white blood cells from a donor attack the body's normal tissues (called graft versus host disease). Removing a particular type of T cell (naive T cells) from the donor cells before the transplant may stop this from happening.
Patients are randomized to 1 of 2 arms. All patients receive 1 of 3 conditioning regimens.
CONDITIONING REGIMEN A: Patients undergo total body irradiation (TBI) twice daily (BID) on days -10 to -7, then receive thiotepa intravenously (IV) over 3 hours once daily (QD) on days -6 and -5, and fludarabine IV over 30 minutes once daily on days -6 to -2.
CONDITIONING REGIMEN B: Patients undergo TBI BID on days -8 to -5, then receive fludarabine IV over 30 minutes QD on days -4 to -2, and cyclophosphamide IV over 1 hour QD on days -3 and -2.
CONDITIONING REGIMEN C: Patients receive fludarabine IV over 30 minutes QD on days -6 to -2, busulfan IV over 180 minutes QD on days -5 to -2, and undergo total body irradiation BID on day -1.
ARM I: Patients receive naive T-cell depleted PBSCs on day 0.
ARM II: Patients receive unmanipulated T cell-replete BM on day 0.
GVHD PROPHYLAXIS: All patients receive tacrolimus IV on days -1 to +50 followed by a taper in the absence of grade II-IV aGVHD. Patients also receive methotrexate IV on days +1, +3, +6, and +11.
Additionally, all patients undergo echocardiography (ECHO) and cerebrospinal fluid (CSF) collection at baseline as well as blood sample collection and bone marrow aspiration with or without biopsy throughout the trial.
After completion of study treatment, patients are followed up at days 28, 56, 90, 180, 270, and 365 and then at months 15, 18, 21, and 24.
110 studies on the registry are indexed under Leukemia, Biphenotypic, Acute; 51 are open to participants now.
This study's enrollment of 45 is close to the median of 50 across 98 interventional studies indexed under Leukemia, Biphenotypic, Acute.
Browse Leukemia, Biphenotypic, Acute studies →Fred Hutchinson Cancer Center is the lead sponsor of 537 studies on the registry; 79 are open to participants now.
Of its 57 completed or terminated interventional studies of FDA-regulated products, 45 (79%) have results posted.
Counted across the registry records on this site, refreshed daily.
The patient must have one of the following diagnoses and be considered to be an appropriate candidate for allogeneic HCT by the study site principal investigator (PI):
Planned product type for infusion is PBSC or BM (i.e. not cord blood):
Diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected for hemoglobin) >= 60% predicted by pulmonary function tests (PFTs)
* Patients who are unable to perform PFTs (age \< 6 years or considered developmentally incapable of PFTs): oxygen saturation (by oximetry) must be >= 92% on room air.
Total bilirubin =\< 2 x upper limit of normal (ULN) (unless value[s] > 2 x ULN are disease- or medication-related).
* If value(s) are > 2 x ULN and not disease- or medication related, patient must be evaluated by a gastrointestinal (GI) physician. If GI physician considers protocol treatment to be contraindicated for the patient, the patient will not be eligible for the study.
Alanine aminotransferase (ALT), aspartate aminotransferase (AST) =\< 2 x ULN (unless value[s] > 2 x ULN are disease- or medication-related).
* If value(s) are > 2 x ULN and not disease- or medication related, patient must be evaluated by a gastrointestinal GI physician. If GI physician considers protocol treatment to be contraindicated for the patient, the patient will not be eligible for the study.
Serum creatinine (SCr) within normal range for age. If SCr is outside normal range for age, creatinine clearance (CrCl) > 40 mL/min/1.73m\^2 must be obtained (measured by 24-hour [hr] urine specimen or nuclear glomerular filtration rate [GFR]).
DONOR: MUDs:
Must meet eligibility criteria as defined by the NMDP or be ineligible with statement of urgent medical need (exception 21 CFR 1271.65(b)(iii))
DONOR: MRDs:
Must meet institutional donor eligibility criteria, or be ineligible with statement that the donor is a first or second degree relative (exception 21 CRF 1271.65(b)(i)).
Exclusion Criteria:
Patient body weight:
CONDITIONING REGIMEN A: Patients undergo TBI BID on days -10 to -7, then receive thiotepa IV over 3 hours QD on days -6 and -5, and fludarabine IV over 30 minutes once daily on days -6 to -2. CONDITIONING REGIMEN B: Patients undergo TBI BID on days -8 to -5, then receive fludarabine IV over 30 minutes QD on days -4 to -2, and cyclophosphamide IV over 1 hour QD on days -3 and -2. CONDITIONING REGIMEN C: Patients receive fludarabine IV over 30 minutes QD on days -6 to -2, busulfan IV over 180 minutes QD on days -5 to -2, and undergo total body irradiation BID on day -1. TRANSPLANT: Patients receive naive T-cell depleted PBSCs on day 0. GVHD PROPHYLAXIS: All patients receive tacrolimus IV beginning on day -1 and methotrexate IV on days 1, 3, 6, and 11. Additionally, patients undergo ECHO and CSF collection at baseline as well as blood sample collection and bone marrow aspiration with or without biopsy throughout the trial.
Radiation: Total-Body Irradiation · Drug: Thiotepa · Drug: Fludarabine · Drug: Cyclophosphamide · Drug: Busulfan · Drug: Tacrolimus · Drug: Methotrexate · Procedure: Naive T Cell-Depleted Hematopoietic Stem Cell Transplantation · Procedure: Echocardiography · Procedure: Biospecimen Collection · Procedure: Bone Marrow Aspiration · Procedure: Bone Marrow Biopsy
CONDITIONING REGIMEN A: Patients undergo TBI BID on days -10 to -7, then receive thiotepa IV over 3 hours QD on days -6 and -5, and fludarabine IV over 30 minutes once daily on days -6 to -2. CONDITIONING REGIMEN B: Patients undergo TBI BID on days -8 to -5, then receive fludarabine IV over 30 minutes QD on days -4 to -2, and cyclophosphamide IV over 1 hour QD on days -3 and -2. CONDITIONING REGIMEN C: Patients receive fludarabine IV over 30 minutes QD on days -6 to -2, busulfan IV over 180 minutes QD on days -5 to -2, and undergo total body irradiation BID on day -1. TRANSPLANT: Patients receive unmanipulated T cell-replete BM on day 0. GVHD PROPHYLAXIS: All patients receive tacrolimus IV beginning on day -1 and methotrexate IV on days 1, 3, 6, and 11. Additionally, patients undergo ECHO and CSF collection at baseline as well as blood sample collection and bone marrow aspiration with or without biopsy throughout the trial.
Radiation: Total-Body Irradiation · Drug: Thiotepa · Drug: Fludarabine · Drug: Cyclophosphamide · Drug: Busulfan · Procedure: Allogeneic Bone Marrow Transplantation · Drug: Tacrolimus · Drug: Methotrexate · Procedure: Echocardiography · Procedure: Biospecimen Collection · Procedure: Bone Marrow Aspiration · Procedure: Bone Marrow Biopsy
Undergo TBI
Also known as: Total Body Irradiation, Whole-Body Irradiation, SCT_TBI, TBI, Whole Body Irradiation
Given IV
Also known as: 1,1',1"-phosphinothioylidynetrisaziridine, Oncotiotepa, STEPA, Tepadina, Tespamin, Tespamine, Thio-Tepa, Thiofosfamide, Thiofozil, Thiophosphamide, Thiophosphoramide, triethylenethiophosphoramide
Given IV
Also known as: 2-Fluoro-9-beta-arabinofuranosyladenine, 2-Fluorovidarabine, Fluradosa
Given IV
Also known as: Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, Cycloblastin, Cytophosphane
Given IV
Also known as: Bussulfam, Busulfanum, Busulfex, Busulphan, Misulban, Misulfan, Mitosan, Myeleukon
Receive unmanipulated T cell replete BM
Also known as: Allo BMT, Allogeneic Blood and Marrow Transplantation, Allogeneic BMT
Given IV
Also known as: Fujimycin, Hecoria, Prograf, Protopic
Given IV
Also known as: Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, Emtexate, Emthexat, Emthexate, Farmitrexat, Medsatrexate, Methoblastin, Rheumatrex
Receive naive T-cell depleted PBSCs
Undergo ECHO
Also known as: EC, ECHO
Undergo CSF and blood sample collection
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Feasibility achievement
Success defined as achievement of cell selection goals for two consecutive Naive T cells (TN)-depleted peripheral blood stem cells (PBSC) hematopoietic cell transplantation (HCTs) at each study site (Feasibility)
Time frame: Up to 2 years
Engraftment of neutrophils by day 28 (Feasibility)
Success defined as achievement neutrophil engraftment (absolute neutrophil count \[ANC\] \>= 500/mm\^3) on first day of three consecutive laboratory values obtained on different days.
Time frame: At day 28
Current-graft versus host disease (GVHD)-free, relapse-free survival (Randomized Controlled Trial [RCT])
Defined as alive, no relapse after HCT, no current GVHD requiring prednisone, no graft rejection or graft failure. The proportion of subjects meeting the primary endpoint will be described in each arm with 90% confidence intervals (CI) and compared between arms using the chi-square test. A two-sided 10% significance level will be used for this comparison.
Time frame: At 1 year
Chronic GVHD (cGVHD) meeting National Institutes of Health (NIH) criteria and requiring prednisone (RCT)
Cumulative incidence curve will be computed for each arm along with a 90% CI at 1 year and 2 years post-HCT. Death and/or relapse prior to occurrence of cGVHD will be considered as competing risks. The cumulative incidence curves will be compared between arms using Gray's test. The maximum severity of cGVHD will also be described in each arm and compared using the chi-squared test.
Time frame: At 1 and 2 years
Proportion of subjects alive and off prednisone (or equivalent systemic corticosteroid) for treatment of GVHD (RCT)
Proportions of subjects alive without requiring use of prednisone (or equivalent systemic corticosteroid) for GVHD will be estimated with 90% CI for both arms at time points over 24 months, and compared using the chi-squared test.
Time frame: At 3, 6, 9, 12, 15, 18, 21 and 24 months post HCT
Plan to share: No
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is active, not recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Leukemia, Biphenotypic, Acute→
Fred Hutchinson Cancer Center