Naive T Cell Depletion for Preventing Chronic Graft-versus-Host Disease in Children and Young Adults With Blood Cancers Undergoing Donor Stem Cell Transplant
NCT ID: NCT03779854
Last Updated: 2025-10-15
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE2
68 participants
INTERVENTIONAL
2019-08-29
2027-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts in Preventing GVHD in Children
NCT01858740
Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors in Preventing GVHD
NCT02220985
Selective Depletion of CD45RA+T Cells From Allogeneic Peripheral Blood Stem Cell Grafts for the Prevention of GVHD
NCT00914940
Removal of T Cells to Prevent Graft-Versus-Host Disease in Patients Undergoing Bone Marrow Transplantation
NCT00005641
Donor Th2 Cells to Prevent Graft-Versus-Host Disease in Bone Marrow Transplants
NCT00001830
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Arm I (chemotherapy, naive T-cell depleted PBSC)
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.
Total-Body Irradiation
Undergo TBI
Thiotepa
Given IV
Fludarabine
Given IV
Cyclophosphamide
Given IV
Busulfan
Given IV
Tacrolimus
Given IV
Methotrexate
Given IV
Naive T Cell-Depleted Hematopoietic Stem Cell Transplantation
Receive naive T-cell depleted PBSCs
Echocardiography
Undergo ECHO
Biospecimen Collection
Undergo CSF and blood sample collection
Bone Marrow Aspiration
Undergo bone marrow aspiration
Bone Marrow Biopsy
Undergo bone marrow biopsy
Arm II (chemotherapy, unmanipulated T cell replete BM)
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.
Total-Body Irradiation
Undergo TBI
Thiotepa
Given IV
Fludarabine
Given IV
Cyclophosphamide
Given IV
Busulfan
Given IV
Allogeneic Bone Marrow Transplantation
Receive unmanipulated T cell replete BM
Tacrolimus
Given IV
Methotrexate
Given IV
Echocardiography
Undergo ECHO
Biospecimen Collection
Undergo CSF and blood sample collection
Bone Marrow Aspiration
Undergo bone marrow aspiration
Bone Marrow Biopsy
Undergo bone marrow biopsy
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Total-Body Irradiation
Undergo TBI
Thiotepa
Given IV
Fludarabine
Given IV
Cyclophosphamide
Given IV
Busulfan
Given IV
Allogeneic Bone Marrow Transplantation
Receive unmanipulated T cell replete BM
Tacrolimus
Given IV
Methotrexate
Given IV
Naive T Cell-Depleted Hematopoietic Stem Cell Transplantation
Receive naive T-cell depleted PBSCs
Echocardiography
Undergo ECHO
Biospecimen Collection
Undergo CSF and blood sample collection
Bone Marrow Aspiration
Undergo bone marrow aspiration
Bone Marrow Biopsy
Undergo bone marrow biopsy
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Acute lymphoblastic leukemia (ALL) with \< 5% marrow blasts.
* Acute myeloid leukemia (AML) with \< 25% marrow blasts.
* Other acute leukemia (OAL) or related neoplasm (including but not limited to acute biphenotypic leukemia \[ABL\], ambiguous lineage \[ALAL\], mixed phenotype acute leukemia \[MPAL\], blastic plasmacytoid dendritic cell neoplasm \[BPDCN\], acute undifferentiated leukemia \[AUL\], lymphoblastic lymphoma, Burkitt leukemia/lymphoma, mast cell leukemia, chronic monocytic leukemia \[CML\] with blast crisis or other chronic myeloproliferative neoplasm) with \< 5% marrow blasts.
* Myelodysplastic syndrome (MDS) with excess blasts (EB-1 and EB-2) and has received cytotoxic induction chemotherapy (excluding small molecule inhibitors and de-methylating agents)
* Age 6 months to 26 years at the time informed consent is obtained using the Informed Consent to Participate in a Research Study form
* Matched related donor (MRD) or matched unrelated donor (MUD) (defined as 8/8 match for human leukocyte antigen \[HLA\]-A, -B, -C, -DRB1).
* Planned product type for infusion is PBSC or BM (i.e. not cord blood):
* For feasibility phase, planned product type for infusion must be PBSC.
* For RCT, planned product type must be PBSC or BM.
* Karnofsky or Lansky score \>= 60%.
* Left ventricular ejection fraction (LVEF) at rest \>= 40%.
* 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 \[GFR\]).
* Age (Years): Maximum SCr (mg/dL)
* =\< 5: 0.8
* 6-10: 1
* 11-15: 1.2
* \> 15: 1.5
* Recipient informed consent/assent/legal guardian permission documentation must be obtained.
* DONOR: May be related (MRD) or unrelated (MUD) to the subject.
* DONOR: Must be matched to the subject at 8/8 HLA alleles (HLA-A, -B, -C, and -DRB1)
* DONOR: Be \>=14 years of age.
* DONOR: Must be available to donate in the United States of America (USA) (i.e. excludes international donors).
* DONOR: Must agree to donate BM or PBSC (i.e. agree to donate whichever product type is requested) (applicable only to the RCT phase of this study).
* DONOR: MUDs:
* Must give informed consent according to applicable National Marrow Donor Program (NMDP) donor regulatory requirements
* 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))
* Tests must be performed using Food and Drug Administration (FDA) licensed, cleared, and approved test kits in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory
* DONOR: MRDs:
* Must be negative for human immunodeficiency virus (HIV)-1, HIV-2, human T-lymphotropic virus (HTLV)-1, HTLV-2, hepatitis B, hepatitis C (serological and/or nucleic acid testing \[NAT\] and/or other approved testing)
* 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)).
* Tests must be performed using FDA licensed, cleared, and approved test kits in a CLIA-certified laboratory.
Exclusion Criteria
* Patients on other experimental protocols for the prevention of GVHD.
* Patient body weight:
* Matched related donor (MRD): \> 100 kg are ineligible
* Matched unrelated donor (MUD): \> 75 kg must be discussed with the protocol principal investigator (PI) prior to enrollment.
* HIV-positive.
* Uncontrolled infections must be evaluated by an infectious disease physician and considered suitable to undergo HCT by the study site PI, infectious disease physician and protocol PI. Upper respiratory tract infection (URI) does not constitute an uncontrolled infection in this context.
* Life expectancy \< 3 months from disease other than acute leukemia or myelodysplastic syndrome (MDS).
* Significant medical condition that would make recipient unsuitable for HCT.
* Prior allogeneic or autologous HCT.
* Females who are pregnant or breastfeeding.
* Patients of child bearing age who are presumed to be fertile and are unwilling to use an effective birth control method or refrain from sexual intercourse during study treatment and for 12 months following HCT.
* Known hypersensitivity to tacrolimus, fludarabine, or methotrexate (MTX).
6 Months
26 Years
ALL
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Cancer Institute (NCI)
NIH
Fred Hutchinson Cancer Center
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Marie Bleakley
Role: PRINCIPAL_INVESTIGATOR
Fred Hutch/University of Washington Cancer Consortium
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Children's Hospital of Los Angeles
Los Angeles, California, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Children's Healthcare of Atlanta
Atlanta, Georgia, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States
Dana Farber / Boston Children's Hospital
Boston, Massachusetts, United States
UH Rainbow Babies and Children's Hospital (University Hospitals Cleveland Medical Center)
Cleveland, Ohio, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Oregon Health and Science University
Portland, Oregon, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
References
Explore related publications, articles, or registry entries linked to this study.
Bleakley M. Naive T-cell depletion in stem cell transplantation. Blood Adv. 2020 Oct 13;4(19):4980. doi: 10.1182/bloodadvances.2020001888.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
9880
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2018-01752
Identifier Type: REGISTRY
Identifier Source: secondary_id
RG1003345
Identifier Type: OTHER
Identifier Source: secondary_id
RG1003345
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.