Naive T Cell Depletion for Preventing Chronic Graft-versus-Host Disease in Children and Young Adults With Blood Cancers Undergoing Donor Stem Cell Transplant

NCT03779854 | Recruiting Phase 2 DMC FDA Drug

• 5 other identifiers: RG10033459880NCI-2018-01752P30CA015704P01CA018029-43
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Acute Biphenotypic Leukemia; Acute Leukemia; Acute Leukemia of Ambiguous Lineage; Acute Lymphoblastic Leukemia; Acute Undifferentiated Leukemia; Allogeneic Hematopoietic Stem Cell Transplantation Recipient; Blastic Plasmacytoid Dendritic Cell Neoplasm; Blasts Under 25 Percent of Bone Marrow Nucleated Cells; Blasts Under 5 Percent of Bone Marrow Nucleated Cells; Mixed Phenotype Acute Leukemia; Myelodysplastic Syndrome With Excess Blasts-1; Myelodysplastic Syndrome/Acute Myeloid Leukemia; Burkitt Leukemia; Chronic Monocytic Leukemia; Lymphoblastic Lymphoma; Mast Cell Leukemia; Myeloproliferative Neoplasm

Outcome Measures

Primary Outcomes (3)

• 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)

  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.

  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.

  At 1 year

Secondary Outcomes (2)

• Chronic GVHD (cGVHD) meeting National Institutes of Health (NIH) criteria and requiring prednisone (RCT)

  At 1 and 2 years

• Proportion of subjects alive and off prednisone (or equivalent systemic corticosteroid) for treatment of GVHD (RCT)

  At 3, 6, 9, 12, 15, 18, 21 and 24 months post HCT

Study Arms (2)

Arm I (chemotherapy, naive T-cell depleted PBSC)

EXPERIMENTAL

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

Arm II (chemotherapy, unmanipulated T cell replete BM)

ACTIVE COMPARATOR

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

Interventions

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: Total Body Irradiation, Whole-Body Irradiation, SCT_TBI, TBI, Whole Body Irradiation

Arm I (chemotherapy, naive T-cell depleted PBSC); Arm II (chemotherapy, unmanipulated T cell replete BM)

Thiotepa DRUG

Given IV

Also known as: 1,1',1"-phosphinothioylidynetrisaziridine, Oncotiotepa, STEPA, Tepadina, Tespamin, Tespamine, Thio-Tepa, Thiofosfamide, Thiofozil, Thiophosphamide, Thiophosphoramide, triethylenethiophosphoramide

Arm I (chemotherapy, naive T-cell depleted PBSC); Arm II (chemotherapy, unmanipulated T cell replete BM)

Fludarabine DRUG

Given IV

Also known as: 2-Fluoro-9-beta-arabinofuranosyladenine, 2-Fluorovidarabine, Fluradosa

Arm I (chemotherapy, naive T-cell depleted PBSC); Arm II (chemotherapy, unmanipulated T cell replete BM)

Cyclophosphamide DRUG

Given IV

Also known as: Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, Cycloblastin, Cytophosphane

Arm I (chemotherapy, naive T-cell depleted PBSC); Arm II (chemotherapy, unmanipulated T cell replete BM)

Busulfan DRUG

Given IV

Also known as: Bussulfam, Busulfanum, Busulfex, Busulphan, Misulban, Misulfan, Mitosan, Myeleukon

Arm I (chemotherapy, naive T-cell depleted PBSC); Arm II (chemotherapy, unmanipulated T cell replete BM)

Allogeneic Bone Marrow Transplantation PROCEDURE

Receive unmanipulated T cell replete BM

Also known as: Allo BMT, Allogeneic Blood and Marrow Transplantation, Allogeneic BMT

Arm II (chemotherapy, unmanipulated T cell replete BM)

Tacrolimus DRUG

Given IV

Also known as: Fujimycin, Hecoria, Prograf, Protopic

Arm I (chemotherapy, naive T-cell depleted PBSC); Arm II (chemotherapy, unmanipulated T cell replete BM)

Methotrexate DRUG

Given IV

Also known as: Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, Emtexate, Emthexat, Emthexate, Farmitrexat, Medsatrexate, Methoblastin, Rheumatrex

Arm I (chemotherapy, naive T-cell depleted PBSC); Arm II (chemotherapy, unmanipulated T cell replete BM)

Naive T Cell-Depleted Hematopoietic Stem Cell Transplantation PROCEDURE

Receive naive T-cell depleted PBSCs

Arm I (chemotherapy, naive T-cell depleted PBSC)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC, ECHO

Arm I (chemotherapy, naive T-cell depleted PBSC); Arm II (chemotherapy, unmanipulated T cell replete BM)

Biospecimen Collection PROCEDURE

Undergo CSF and blood sample collection

Arm I (chemotherapy, naive T-cell depleted PBSC); Arm II (chemotherapy, unmanipulated T cell replete BM)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Arm I (chemotherapy, naive T-cell depleted PBSC); Arm II (chemotherapy, unmanipulated T cell replete BM)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Arm I (chemotherapy, naive T-cell depleted PBSC); Arm II (chemotherapy, unmanipulated T cell replete BM)

Eligibility Criteria

• Age: 6 Months - 26 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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):
• 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).

You may not qualify if:

• Active central nervous system (CNS) disease. A patient may have a history of CNS disease; however, any CNS disease must be cleared by the end of the pre-conditioning evaluation. If CNS disease is identified on the first cerebrospinal fluid (CSF) evaluation within 30 days of the start of the preparative regimen, a repeat CSF evaluation must be performed and show no evidence of disease in order for the patient to be eligible for the protocol.
• 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).

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (10)

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

RECRUITING

Children's National Medical Center

Washington D.C., District of Columbia, 200100, United States

WITHDRAWN

Children's Healthcare of Atlanta

Atlanta, Georgia, 30329, United States

NOT YET RECRUITING

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

RECRUITING

Dana Farber / Boston Children's Hospital

Boston, Massachusetts, 02115, United States

NOT YET RECRUITING

UH Rainbow Babies and Children's Hospital (University Hospitals Cleveland Medical Center)

Cleveland, Ohio, 44106, United States

NOT YET RECRUITING

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

RECRUITING

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

Related Publications (1)

• Bleakley M. Naive T-cell depletion in stem cell transplantation. Blood Adv. 2020 Oct 13;4(19):4980. doi: 10.1182/bloodadvances.2020001888.

  PMID: 33049057 DERIVED

MeSH Terms

Conditions

Leukemia, Biphenotypic, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Blastic Plasmacytoid Dendritic Cell Neoplasm; GATA2 Deficiency; Burkitt Lymphoma; Leukemia, Myeloid; Leukemia, Mast-Cell; Myeloproliferative Disorders

Interventions

Whole-Body Irradiation; Thiotepa; fludarabine; fludarabine phosphate; Cyclophosphamide; Busulfan; Bone Marrow Transplantation; Tacrolimus; Methotrexate

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Histiocytic Disorders, Malignant; Lymphoma; Hematologic Neoplasms; Neoplasms by Site; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Leukemia, Myeloid, Acute; Mastocytosis, Systemic; Mastocytosis; Mast Cell Activation Disorders

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques; Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative; Macrolides; Lactones; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Marie Bleakley

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marie Bleakley

CONTACT

206-667-6572; mbleakle@fredhutch.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2018
• First Posted: December 19, 2018
• Study Start: August 29, 2019
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: October 15, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)