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Active, not recruitingNCT03663933Updated Mar 17, 2026Results posted

Allogeneic Hematopoietic Cell Transplantation for Disorders of T-cell Proliferation and/or Dysregulation

A Phase 2 interventional study of e-ATG and Immunosuppression Only Conditioning in Lymphoproliferative Disorders, Autoimmune Lymphoproliferative and Primary T-cell Immunodeficiency Disorders, sponsored by National Cancer Institute (NCI). Active, not recruiting at 2 sites in United States. Open to participants aged 4 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-03-17.

Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
71
Allocation
Non-randomized
Ages
4 Years and older
Sex
All
01

Study summary

Background:

Blood stem cells in the bone marrow make all the cells to normally defend a body against disease. Allogeneic blood or marrow transplant is when these stem cells are transferred from one person to another. Researchers think this treatment can provide a new, healthy immune system to correct T-cell problems in some people.

Objective:

To see if allogeneic blood or bone marrow transplant is safe and effective in treating people with T-cell problems.

Eligibility:

Donors: Healthy people ages 4 and older

Recipients: People the same age with abnormal T-cell function causing health problems

Design:

All participants will be screened with:

  • Medical history
  • Physical exam
  • Blood, heart, and urine tests

Donors will also have an electrocardiogram and chest x-ray. They may have veins tested or a pre-anesthesia test.

Recipients will also have lung tests.

Some participants will have scans and/or bone marrow collected by needle in the hip bones.

Donors will learn about medicines and activities to avoid and repeat some screening tests.

Some donors will stay in the hospital overnight and have bone marrow collected with anesthesia.

Other donors will get shots for several days to stimulate cells. They will have blood removed by plastic tube (IV) in an arm vein. A machine will remove stem cells and return the rest of the blood to the other arm.

Recipients will have:

  • More bone marrow and a small fragment of bone removed
  • Dental, diet, and social worker consultations
  • Scans
  • Chemotherapy and antibody therapy for 2 weeks
  • Catheter inserted in a chest or neck vein to receive donor stem cells
  • A hospital stay for several weeks with more medicines and procedures
  • Multiple follow-up visits
Read the detailed description

Background:

  • Disorders of T-cell proliferation and/or dysregulation (TCP/D) can lead to T-cell lymphoproliferative disorders, autoimmunity, infection, and aberrant immune activation with resulting organ dysfunction, morbidity, and mortality.
  • Allogeneic hematopoietic cell transplantation (HCT) has the potential to cure disorders of TCP/D.
  • Subjects with TCP/D may be at higher risk for graft rejection and/or disease relapse.

Primary Objective:

- Separately by arm: To estimate the percentage of recipients with >50% donor T cell chimerism and graft-failure free survival at day +180 post-HCT

Eligibility:

  • Age greater than or equal to 4 years
  • TCP/D deemed to be of sufficient past severity to warrant HCT that meets at least one of the criteria below:

    • Identified germline T-cell activating mutation in the PI3k pathway
    • Identified adenosine deaminase 2 (ADA2) deficiency (biallelic mutations in CECR1 (ADA2) and/or phenotypically with low ADA2 level) leading to neutropenia requiring chronic granulocyte colony-stimulating factor (GCSF) therapy or to transfusion-dependent anemia or thrombocytopenia
    • T-cell infiltration of liver, spleen, lymph nodes, marrow, lungs, gut, or other organs by T cells, as evidenced by laboratory, radiographic, and/or anatomic pathology evaluation, resulting in organ dysfunction and/or organomegaly
    • Latent herpesvirus infection in T lymphocytes
    • History of or active evidence of hemophagocytic lymphohistiocytosis (HLH)
    • Recurrent or prolonged fevers attributed to immune dysregulation
    • T-cell population in blood and/or marrow with immunophenotype of large granular lymphocytes (LGL), with or without clonality or lymphocytosis
    • T-cell lymphoproliferative disorder in the setting of an underlying immune defect
    • Immune-mediated cytopenias of one lineage requiring transfusion or GCSF support or of 2 or 3 lineages with or without transfusion or support
    • Chronic active Epstein-Barr virus (EBV)
  • At least one potentially suitable 7-8/8 human leukocyte antigen (HLA)-matched related or unrelated donor, or an HLA-haploidentical related donor
  • Adequate end-organ function
  • Not pregnant or breastfeeding
  • Human immunodeficiency virus (HIV) negative
  • Disease status: Subjects with malignancy should be referred in remission for evaluation, if possible, although the aggressive nature of many of these diseases necessitates the potential need to enroll subjects onto study and treat with standard therapies before proceeding to protocol therapy (HCT)

Design:

  • There will be two arms that vary in conditioning intensity - an immunosuppression-only conditioning (IOC) arm for high-risk subjects and a reduced-intensity conditioning (RIC) arm.
  • IOC arm: equine anti-thymocyte globulin (e-ATG) 40 mg/kg/day intravenous (IV) on days -14 and -13, pentostatin 4 mg/m\^2/day IV on days -9 and -5, low-dose cyclophosphamide orally daily on days -9 through -2
  • RIC arm: e-ATG 40 mg/kg/day IV on days -14 and -13, pentostatin 4 mg/m\^2/day IV on days -11 and -7, low-dose cyclophosphamide orally daily on days -11 through -4; busulfan IV, pharmacokinetically dosed, on days -3 and -2.

    -- Subjects will be assigned to the IOC arm if there is significant end-organ dysfunction present and it is felt that a conditioning regimen that includes busulfan would likely be associated with intolerable or life-threatening toxicities for the subject. Subjects will also be assigned to the IOC arm if they possess a deoxyribonucleic acid (DNA) repair defect, telomere maintenance defect, or familial cancer predisposition syndrome that necessitates limiting chemotherapy as much as possible to prevent future cancer risk.

  • Peripheral blood stem cells are the preferred graft source, although bone marrow is permitted
  • Graft-versus-host disease (GVHD) prophylaxis:

    • Post-transplant cyclophosphamide (PTCy) on days +3 and +4 (50 mg/kg/day on RIC arm and 25 mg/kg/day on the IOC arm, with the option of 25 mg/kg/day on the RIC arm), tacrolimus on days +5 through +90, and mycophenolate mofetil (MMF) on days +5 through +25.
02

Conditions studied

  • Lymphoproliferative Disorders
  • Autoimmune Lymphoproliferative
  • Primary T-cell Immunodeficiency Disorders
  • Immune System Diseases
  • Common Variable Immunodeficiency

Keywords

  • Haploidentical
  • Autoimmunity
  • Immune Dysregulation
  • Congenital
  • Opportunistic Infection
03

Who can participate

Ages eligible
4 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes

Eligibility criteria

  • INCLUSION CRITERIA - RECIPIENT:
  • Age >= 4 years
  • T-cell proliferation and/or dysregulation (TCP/D) deemed to be of sufficient past severity to warrant hematopoietic cell transplantation (HCT) that meets at least one of the criteria below:

    • Identified germline T-cell activating mutation in the phosphoinositide 3-kinase (PI3k) pathway
    • Identified adenosine deaminase 2 (ADA2) deficiency (biallelic mutations in CECR1 (ADA2) and/or phenotypically with low ADA2 level) leading to neutropenia requiring chronic granulocyte colony-stimulating factor (GCSF) therapy or to transfusion-dependent anemia or thrombocytopenia
    • T-cell infiltration of liver, spleen, lymph nodes, marrow, lungs, gut, or other organs by T cells, as evidenced by laboratory, radiographic, and/or anatomic pathology evaluation, resulting in organ dysfunction and/or organomegaly
    • Latent herpesvirus infection in T lymphocytes
    • History of or active evidence of hemophagocytic lymphohistiocytosis (HLH)
    • Recurrent or prolonged fevers attributed to immune dysregulation
    • T-cell population in blood and/or marrow with immunophenotype of large granular lymphocytes (LGL), with or without clonality or lymphocytosis
    • T-cell lymphoproliferative disorder in the setting of an underlying immune defect
    • Immune-mediated cytopenias of one lineage requiring transfusion or GCSF support or of 2 or 3 lineages with or without transfusion or support
    • Chronic active Epstein-Barr virus (EBV)
  • At least one potential 7-8/8 human leukocyte antigen (HLA)-matched related (excluding an identical twin) or unrelated donor (at HLA-A, -B, -C, and -DR), or an HLA-haploidentical related donor, based on initial low resolution unrelated donor search and/or at least one biologically- related family member who has at least a 25% chance of being at minimum an HLA- haploidentical match and is potentially suitable to donate based on reported family history. HLA typing of potential donors and/or mutation testing does not need to be completed for eligibility.
  • Adequate end-organ function, as measured by:

    • Left ventricular ejection fraction (LVEF) greater than or equal to 40% by 2-dimensional (2D) echocardiogram (ECHO) or left ventricular shortening fraction greater than or equal to 20% by ECHO for subjects receiving reduced-intensity conditioning (RIC), or LVEF greater than or equal to 30% if the subject has radiologic evidence of aortic, renal, or coronary artery vasculitis. LVEF greater than or equal to 30% for subjects receiving immunosuppression-only conditioning (IOC).
    • Pulmonary function tests: diffusing capacity of the lungs for carbon monoxide (DLco) (corrected for hemoglobin) and forced expiratory volume (FEV1) greater than or equal to 40% of predicted for the RIC arm, and greater than or equal to 30% predicted for the IOC arm; or in pediatric subjects, if unable to perform pulmonary function tests, there should be no evidence of dyspnea at rest, no requirement for supplemental oxygen, and oxygen saturation >92% on room air. Calculations will be based on the values reported in (Clinical Research Information System (CRIS).
    • Bilirubin \<= 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis) for subjects receiving RIC and bilirubin \<= 5.0 mg/dL for subjects receiving IOC (unless due to Gilbert's syndrome or hemolysis); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<= 5 x upper limit of normal (ULN) for subjects receiving RIC or \<= 10 x ULN for subjects receiving IOC. Subjects who are above these bilirubin, ALT, or AST thresholds may be eligible for the RIC or IOC arm if evaluated by a hepatologist who deems the liver function test abnormalities to be potentially reversible with HCT.
    • Estimated creatinine clearance of >= 50 mL/min/1.73 m\^2, calculated using estimated glomerular filtration rate (eGRF) in the clinical lab for adults and the Schwartz formula for pediatric subjects, if eGFR not reported by the clinical lab.
  • Karnofsky (adults) or Lansky (children) performance status of >= 50% or Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less for the RIC arm and >=30% or ECOG performance status of 3 or less for the IOC arm
  • Ability of subject or parent/legal guardian or Legally Authorized Representative (LAR) (e.g., in cases of adults unable to consent) to understand and the willingness to sign a written informed consent document
  • Not pregnant or breastfeeding. As therapeutic agents used in this trial may be harmful to a fetus, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for at least one-year post-allo HCT. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in the study, she should inform her treating physician immediately.
  • Disease status: Subjects with lymphoproliferative disorder (LPD), large granular lymphocytic leukemia (LGL), hemophagocytic lymphohistiocytosis (HLH), or other TCP/D disorders requiring standard therapies to prepare for HCT should be referred in remission if possible. However, these diseases are often aggressive and require swift evaluation for HCT while concurrently attempting to establish disease control through the administration of standard therapies. If ongoing therapy for the underlying disease outside of the National Institutes of Health (NIH) is not in the best interest of the subject according to the clinical judgment of the principal investigator (PI), then the subject may receive standard treatment for his/her underlying TCP/D disorder as a bridge to HCT on this protocol, prior to starting the research phase of the study. If it becomes apparent that the subject will not be able to proceed to HCT, then he/she must come off study. Subjects receiving standard therapy will be told about the therapy, associated risks, potential benefits, alternatives to the proposed therapy, and the availability of receiving the same treatment elsewhere, outside of a research protocol.

EXCLUSION CRITERIA - RECIPIENT:

  • Subjects who are receiving any other investigational agents, with the exception of virus- specific cytotoxic T-cells for the treatment of viral infection/reactivation prior to allo HCT.
  • Prohibitive allergy to a study drug or to compounds of similar chemical or biologic composition of the agents (equine anti-thymocyte globulin (e-ATG), steroids, cyclophosphamide, busulfan, pentostatin, tacrolimus, mycophenolate mofetil (MMF), G-CSF) used in the study.
  • Active psychiatric disorder which is deemed by the PI to have significant risk of compromising compliance with the transplant protocol, or which does not allow for appropriate informed consent
  • Human immunodeficiency virus (HIV) positive or other acquired immunodeficiency that, as determined by the PI, interferes with the assessment of TCP/D severity and/or the attribution of clinical manifestations of immunodeficiency to a disorder of TCP/D.
  • Magnesium Transporter 1 (MagT1) mutation and active need to take anti-platelet agents and/or therapeutic anti- coagulation that cannot be interrupted during aplasia
  • Lack of adequate central venous access potential

INCLUSION CRITERIA RELATED DONOR

  • Age greater than or equal to 4 years
  • Related donor deemed suitable and eligible, and willing to donate, per clinical evaluations who are additionally willing to donate blood, urine, and marrow specimens for research. Related donors will be evaluated in accordance with existing Standard Policies and Procedures for determination of eligibility and suitability for clinical donation. Note that participation in this study is offered to all related donors, but is not required for clinical donation, so it is possible that not all related donors will enroll onto this study.

EXCLUSION CRITERIA - RELATED DONOR:

-None

INCLUSION CRITERIA - UNRELATED DONOR:

-Unrelated donors will be evaluated in accordance with existing National Marrow Donor Program (NMDP) Standard Policies and Procedures, available at: http://bethematch.org/About-Us/Global- transplant-network/Standards/, except for the additional requirement of EBV serostatus testing for clinical purposes of donor selection. Note that participation in this study is offered to all unrelated donors but not required for clinical donation, so it is possible that not all unrelated donors will enroll on this study. Unrelated donors only enroll if they contribute research specimens, which is optional.

EXCLUSION CRITERIA - UNRELATED DONOR:

-Unrelated donors: failure to qualify as a National Marrow Donor Program (NMDP) donor per current NMDP Standards, available at: http://bethematch.org/About-Us/Global-transplant-network/Standards/. Exceptions to donor eligibility (e.g. foreign travel, tattoos) do not automatically exclude the donor and will be reviewed by the PI.

04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
71 participants (actual)

Study arms

  • Experimental
    Arm 1/Reduced-Intensity Conditioning (RIC)

    Reduced Intensity Conditioning Arm.

    Drug: e-ATG · Procedure: Immunosuppression Only Conditioning · Procedure: Reduced Intensity Conditioning · Drug: GVHD Prophylaxis · Procedure: Allogeneic HSC · Drug: Bisulfan · Drug: Prednisone · Drug: Cyclophosphamide · Drug: MMF · Drug: Mesna · Drug: Tacrolimus · Drug: Pentostatin · Diagnostic Test: PFTs · Diagnostic Test: DEXA · Procedure: Bone Marrow Aspirate & Biopsy · Diagnostic Test: EKG · Diagnostic Test: 2D ECHO

  • Experimental
    Arm 2/Immunosuppression-only Conditioning (IOC)

    Immunosuppression Only Conditioning Arm.

    Drug: e-ATG · Procedure: Immunosuppression Only Conditioning · Drug: GVHD Prophylaxis · Procedure: Allogeneic HSC · Drug: Bisulfan · Drug: Prednisone · Drug: Cyclophosphamide · Drug: MMF · Drug: Mesna · Drug: Tacrolimus · Drug: Pentostatin · Diagnostic Test: PFTs · Diagnostic Test: DEXA · Procedure: Bone Marrow Aspirate & Biopsy · Diagnostic Test: EKG · Diagnostic Test: 2D ECHO

  • No intervention
    Arm 3/Donor

    Healthy Donor- Donors for recipients in arm 1 or arm 2.

Interventions

  • Druge-ATG

    During Immunosuppression Only Conditioning (IOC) and Reduced Intensity Conditioning (RIC).

    Also known as: Antithymocyte Globulin (Equine), Atgam

  • ProcedureImmunosuppression Only Conditioning

    Equine anti-thymocyte globulin (e-ATG) 40 mg/kg intravenous (IV) once daily for days -14 and -13. Prednisone: Tapering doses, given orally daily, and given prior to each daily dose of e-ATG on days -14 and -13, Pentostatin:4 mg/m\^2/day IV on days -9 and -5, cyclophosphamide:5 mg/kg orally daily on days -9 through -2.

    Also known as: IOC

  • ProcedureReduced Intensity Conditioning

    Equine anti-thymocyte globulin (e-ATG) 40 mg/kg intravenous (IV) once daily for days -14 and -13. Prednisone: Tapering doses, given orally daily, and given prior to each daily dose of e-ATG on days -14 and -13, Pentostatin:4 mg/m\^2/day IV on days -11 and -7, cyclophosphamide: 5 mg/kg orally daily on days -11 through -4, Busulfan IV, pharmacokinetically dosed, on days -3 and -2.

    Also known as: RIC

  • DrugGVHD Prophylaxis

    High-dose, post-transplantation cyclophosphamide (PTCy) 25-50 mg/kg on days +3 and +4, Mesna: 25-50 mg/kg weight-based dosing, Tacrolimus 0.02 mg/kg on days +5 through +90, and mycophenolate mofetil (MMF) 15 mg/kg on days +5 through +25.

    Also known as: Graft-versus-host disease prophylaxis

  • ProcedureAllogeneic HSC

    Stem cell transplant

    Also known as: Allogeneic hematopoietic stem cell (HSC)

  • DrugBisulfan

    During Reduced Intensity Conditioning (RIC).

    Also known as: Busulfex, Myleran

  • DrugPrednisone

    During Immunosuppression Only Conditioning (IOC) and Reduced Intensity Conditioning (RIC).

    Also known as: Deltasone

  • DrugCyclophosphamide

    During Immunosuppression Only Conditioning (IOC), Reduced Intensity Conditioning (RIC) and Graft-versus-host disease prophylaxis (GVHD).

    Also known as: Cytoxan, Neosar

  • DrugMMF

    During Graft-versus-host disease prophylaxis (GVHD).

    Also known as: Mycophenolate mofetil, CellCept

  • DrugMesna

    During Graft-versus-host disease prophylaxis (GVHD).

    Also known as: Mesnex, Uromitexan

  • DrugTacrolimus

    During Graft-versus-host disease prophylaxis (GVHD).

    Also known as: Prograf

  • DrugPentostatin

    During Immunosuppression Only Conditioning (IOC) and Reduced Intensity Conditioning (RIC).

    Also known as: Nipent, Deoxycoformycin

  • Diagnostic testPFTs

    Screening ≤4 weeks pretreatment (rx), Day +180 (≤ 14 days), Day +36 (± 21 days), Day +548 (18 months) (± 28 days), and at 2 years and yearly thereafter through +5 years (± 56 days).

    Also known as: Pulmonary function tests

  • Diagnostic testDEXA

    Baseline, Day +365 (± 21 days), at 2 years and yearly thereafter through +5 years (± 56 days), and as clinically indicated after hematopoietic cell transplant (HCT).

    Also known as: Dual-energy x-ray absorptiometry

  • ProcedureBone Marrow Aspirate & Biopsy

    Baseline, Day +60 (± 3 days) and Day +365 (±21 days).

    Also known as: BM aspirate & bx

  • Diagnostic testEKG

    Baseline

    Also known as: Electrocardiogram

  • Diagnostic test2D ECHO

    Screening ≤4 weeks pretreatment (rx), Day +180 (≤ 14 days), Day +36 (± 21 days), Day +548 (18 months) (± 28 days), and at 2 years and yearly thereafter through +5 years (± 56 days).

    Also known as: 2-dimensional echocardiogram

05

What researchers measure

Primary outcomes

  1. Percentage of Recipients Who Are Alive With >50% Donor T Cell Chimerism and Graft-failure Free at 180 Days Post Hematopoietic Cell Transplant (HCT) Reported With an 80% Confidence Interval

    Percentage of recipients with \> 50% donor T cell chimerism and without death or graft failure. A graft failure event is defined as either primary or secondary graft failure, in the absence of a recurrent marrow malignancy.

    Time frame: Day +180 post-HCT

  2. Percentage of Recipients Who Are Alive With >50% Donor T Cell Chimerism and Graft-failure Free at 180 Days Post Hematopoietic Cell Transplant (HCT) Reported With a 95% Confidence Interval

    Percentage of recipients with \> 50% donor T cell chimerism and without death or graft failure. A graft failure event is defined as either primary or secondary graft failure, in the absence of a recurrent marrow malignancy.

    Time frame: Day +180 post -HCT

Secondary outcomes

  1. Cumulative Incidence of Transplant-related Mortality

    Cumulative incidence of transplant-related mortality at 180 days and 1-year post-transplant. Transplant related mortality is defined as any death that occurs outside the setting of the hematopoietic cell transplant (HCT) post-allogeneic relapse of a pre-transplant malignancy or lymphoid disorder.

    Time frame: Day +180, and 1-year post-transplant

  2. Cumulative Incidence of Secondary Graft Failure

    Cumulative incidence of secondary graft failure at 1-year post-transplant. Secondary graft failure is defined as initial blood or marrow donor myeloid chimerism ≥5%, declining to \<5% on subsequent measurements. \<5% indicates graft failure (undesirable outcome).

    Time frame: 1-, 3-, and 5-years post-transplant

  3. Percent Probability of Overall Survival (OS)

    OS is defined as the time in whole days from hematopoietic cell transplantation (HCT) to death from any cause, with surviving recipients censored at the time of last contact.

    Time frame: 1-, 3-, and 5-years post-transplant

  4. Percentage of Participants Who Achieve Chimerism at Stated Days Between Those Who Have Failed by Day 60 or Have Not

    Percentage of participants who achieve early chimerism (\>50% T cell chimerism) at stated days between those who have failed by day 60 or have not. Comparison to be performed using Fisher's exact test. Chimerism is the percentage of donor cells in the peripheral blood.

    Time frame: Day +21, +28, +35, +42, and +60 after hematopoietic cell transplant (HCT)

  5. Percentage of Donor T-cell Populations at Days +28, +42, +60, +100, +180, and 1-year Post Hematopoietic Cell Transplant (HCT)

    The percentage of donor T-cell populations at days +28, +42, +60, +100, +180, and 1-year post hematopoietic cell transplant.

    Time frame: Days +28, +42, +60, +100, +180, and 1-year post hematopoietic cell transplant

  6. Cumulative Incidence of Chronic Graft-versus-host Disease (cGVHD)

    Cumulative incidence curves of chronic graft versus host disease and two-sided 95% confidence intervals at 1 and 2-years post -transplant. cGVHD was scored according to the 2014 National Institutes of Health (NIH) Consensus Criteria for Clinical Trials in Chronic GVHD. Eight organs will be scored on a 0-3 scale.

    Time frame: 1 and 2-years post-transplant

  7. Cumulative Incidence of Acute Graft-versus-host Disease (aGVHD) at 1 Year

    Cumulative incidence curves of acute graft versus host disease and two-sided 95% confidence intervals at 1-year post transplant according to Keystone Criteria of the 1994 Consensus Conference on Acute GVHD Grading. Acute GVHD is defined as any grade, grade 2, 3, or 4 and grade 3-4 acute GVHD. The Keystone criteria provide the basis for grading acute GVHD as follows: Organ-Specific Staging: Each affected organ (skin, liver, gut) is staged 0 (absent) to 4 (severe). Overall Grading (I-IV): Based on the most severe organ involvement. Skin (Grade 0-4): Based on % body surface area (BSA) involvement (e.g., \<25% for Grade 1, \>50% for Grade 3, bullae for Grade 4). Liver (Grade 0-4): Based on total serum bilirubin levels (e.g., 2-2.9 mg/dL for Grade 1, \>15 mg/dL for Grade 4). Gut (Grade 0-4): Based on diarrhea volume and severity (e.g., \>500 mL/day for Grade 1, \>2000 mL/day or ileus/severe pain for Grade 4). Upper GI: Included for classification, with specific criteria for staging.

    Time frame: 1-year post-transplant

  8. Percent Probability Event-free Survival (EFS)

    EFS is defined as the time from transplant to death of any cause or other event, including disease relapse, graft failure, grade 3-4 acute graft versus host disease (GVHD), chronic GVHD requiring systemic therapy, or receipt of post-transplant donor cell infusion.

    Time frame: 1, 3, and 5-years post-transplant

  9. Cumulative Incidence of Primary Graft Failure at Day +60

    Primary graft failure at day +60 estimated using cumulative incidence curves and 95% two-sided confidence intervals. Primary graft failure is defined as \< 5% donor myeloid chimerism in blood and/or bone marrow on all evaluations up to and including day +60, in the absence of a recurrent marrow malignancy.

    Time frame: Day +60

  10. Percentage of Participants With Lymphoproliferative Disease/Lymphoma Relapse at 1, 3, and 5-years Post-hematopoietic Cell Transplant (HCT)

    Lymphoproliferative disease/lymphoma relapse at 1, 3, and 5-years post-HCT estimated using cumulative incidence curves and two-sided 95% confidence intervals at each timepoint.

    Time frame: 1, 3, and 5 years post-HCT

  11. Percent Probability Graft Versus Host Disease (GVHD)-Free Graft Failure-free Survival (GGFS)

    Probabilities of GGFS were estimated using the Kaplan-Meier method. GGFS is

    Time frame: 1, 3, and 5 years post-hematopoietic cell transplant (HCT)

  12. Percent Probability of Graft Versus Host Disease (GVHD)-Free Relapse-free Survival (GRFS)

    GRFS was estimated using the Kaplan-Meier method. Relapse free survival is

    Time frame: 1, 3 and 5-years post-hematopoietic cell transplant (HCT)

  13. Cumulative Incidences of Cytomegalovirus (CMV), BK Virus (BK), Adenovirus, Human Herpes Virus 6 (HHV6), JC Virus (JCV), and Epstein-Barr Virus (EBV) Detection in Blood at Day +100 Post-HCT

    Cumulative incidences of CMV, BK, adenovirus, HHV6, JCV, and EBV detection in blood at day +100 post-HCT estimated using cumulative incidence curves along with two-sided 95% confidence intervals.

    Time frame: day +100 post-HCT

  14. Percentage of Donor B-cell Populations at Days +28, +42, +60, +100, +180, and 1-year Post-transplant

    The percentage of donor B-cell populations at days +28, +42, +60, +100, +180, and 1-year post-transplant.

    Time frame: Days +28, +42, +60, +100, +180, and 1-year post-transplant

  15. Percentage of Donor Natural Killer (NK-) Cell Populations at Days +28, +42, +60, +100, +180, and 1-year Post Transplant

    Percentage of donor natural killer (NK-) cell populations at days +28, +42, +60, +100, +180, and 1-year post transplant.

    Time frame: Days +28, +42, +60, +100, +180, and 1-year post transplant

  16. Percentage of Donor Myeloid Cell Populations at Days +28, +42, +60, +100, +180, and 1-year Post Transplant

    Percentage of donor myeloid cell populations at days +28, +42, +60, +100, +180, and 1-year post transplant.

    Time frame: Days +28, +42, +60, +100, +180, and 1-year post transplant

Other outcomes

  1. Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

    Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

    Time frame: Conditioning start until return to baseline/stabilization, 30 days post-therapy end, removal from therapy, or off study, whichever comes first for all AEs, followed by AE collection per principal investigator discretion, on average 2 years.

06

Results

Posted Mar 17, 2026

Participant flow

Participant flow — Overall Study
MilestoneReduced Intensity Conditioning+Allogeneic Hematopoietic Cell Transplant + Graft-versus-Host DiseaseImmunosuppression-Only Conditioning + Allo Hematopoietic Cell Transplant +Graft-versus-Host Disease7-8/8 Human Leukocyte Antigen (HLA)-Matched Related or Unrelated, or HLA-haploidentical DonorParticipants Enrolled But Not TreatedNational Marrow Donor Program (NMDP) Donors
Started254102012
Completed follow-up period91006
Completed91306
Not completed1637206
Withdrew: Screen failures000200
Withdrew: Death42000
Withdrew: Donor is not removed until recipient completes follow up00706
Withdrew: Graft failure01000
Withdrew: Less than 5 years post-transplant120000

Outcome measures

PrimaryPercentage of Recipients Who Are Alive With >50% Donor T Cell Chimerism and Graft-failure Free at 180 Days Post Hematopoietic Cell Transplant (HCT) Reported With an 80% Confidence Interval

Percentage of recipients with \> 50% donor T cell chimerism and without death or graft failure. A graft failure event is defined as either primary or secondary graft failure, in the absence of a recurrent marrow malignancy.

Time frame:
Day +180 post-HCT
Reported as:
Number · Percentage of participants
Percentage of Recipients Who Are Alive With >50% Donor T Cell Chimerism and Graft-failure Free at 180 Days Post Hematopoietic Cell Transplant (HCT) Reported With an 80% Confidence Interval
Percentage of participantsReduced Intensity Conditioning+Allogeneic Hematopoietic Cell Transplant + Graft-versus-Host DiseaseImmunosuppression-Only Conditioning + Allo Hematopoietic Cell Transplant +Graft-versus-Host Disease
Percentage of Recipients Who Are Alive With >50% Donor T Cell Chimerism and Graft-failure Free at 180 Days Post Hematopoietic Cell Transplant (HCT) Reported With an 80% Confidence Interval80 (69.7 to 90.3)25 (-2.7 to 52.7)
PrimaryPercentage of Recipients Who Are Alive With >50% Donor T Cell Chimerism and Graft-failure Free at 180 Days Post Hematopoietic Cell Transplant (HCT) Reported With a 95% Confidence Interval

Percentage of recipients with \> 50% donor T cell chimerism and without death or graft failure. A graft failure event is defined as either primary or secondary graft failure, in the absence of a recurrent marrow malignancy.

Time frame:
Day +180 post -HCT
Reported as:
Number · Percentage of participants
Percentage of Recipients Who Are Alive With >50% Donor T Cell Chimerism and Graft-failure Free at 180 Days Post Hematopoietic Cell Transplant (HCT) Reported With a 95% Confidence Interval
Percentage of participantsReduced Intensity Conditioning+Allogeneic Hematopoietic Cell Transplant + Graft-versus-Host DiseaseImmunosuppression-Only Conditioning + Allo Hematopoietic Cell Transplant +Graft-versus-Host Disease
Percentage of Recipients Who Are Alive With >50% Donor T Cell Chimerism and Graft-failure Free at 180 Days Post Hematopoietic Cell Transplant (HCT) Reported With a 95% Confidence Interval80 (64.3 to 95.7)25 (-17.4 to 67.4)
SecondaryCumulative Incidence of Transplant-related Mortality

Cumulative incidence of transplant-related mortality at 180 days and 1-year post-transplant. Transplant related mortality is defined as any death that occurs outside the setting of the hematopoietic cell transplant (HCT) post-allogeneic relapse of a pre-transplant malignancy or lymphoid disorder.

Time frame:
Day +180, and 1-year post-transplant
Reported as:
Number · percent of participants
Cumulative Incidence of Transplant-related Mortality
percent of participantsReduced Intensity Conditioning+Allogeneic Hematopoietic Cell Transplant + Graft-versus-Host DiseaseImmunosuppression-Only Conditioning + Allo Hematopoietic Cell Transplant +Graft-versus-Host Disease
Day +180 post-transplant1250
1-year post-transplant1250
SecondaryCumulative Incidence of Secondary Graft Failure

Cumulative incidence of secondary graft failure at 1-year post-transplant. Secondary graft failure is defined as initial blood or marrow donor myeloid chimerism ≥5%, declining to \<5% on subsequent measurements. \<5% indicates graft failure (undesirable outcome).

Time frame:
1-, 3-, and 5-years post-transplant

Results for this outcome have not been posted.

SecondaryPercent Probability of Overall Survival (OS)

OS is defined as the time in whole days from hematopoietic cell transplantation (HCT) to death from any cause, with surviving recipients censored at the time of last contact.

Time frame:
1-, 3-, and 5-years post-transplant

Results for this outcome have not been posted.

SecondaryPercentage of Participants Who Achieve Chimerism at Stated Days Between Those Who Have Failed by Day 60 or Have Not

Percentage of participants who achieve early chimerism (\>50% T cell chimerism) at stated days between those who have failed by day 60 or have not. Comparison to be performed using Fisher's exact test. Chimerism is the percentage of donor cells in the peripheral blood.

Time frame:
Day +21, +28, +35, +42, and +60 after hematopoietic cell transplant (HCT)
Reported as:
Number · Percentage of participants
Percentage of Participants Who Achieve Chimerism at Stated Days Between Those Who Have Failed by Day 60 or Have Not
Percentage of participantsArm 1: Participants Who Achieved >50% T Cell Chimerism by Day +60Arm 1: Participants Who Failed to Achieve >50% T Cell Chimerism by Day +60Arm 2: Participants Who Achieved >50% T Cell Chimerism by Day +60Arm 2: Participants Who Failed to Achieve >50% T Cell Chimerism by Day +60
(>50% T cell chimerism at +21 days post-HCT69—100NA
(>50% T cell chimerism at +28 days post-HCT85—100—
(>50% T cell chimerism at +35 days post-HCT83—100NA
(>50% T cell chimerism at +42 days post-HCT84—100—
SecondaryPercentage of Donor T-cell Populations at Days +28, +42, +60, +100, +180, and 1-year Post Hematopoietic Cell Transplant (HCT)

The percentage of donor T-cell populations at days +28, +42, +60, +100, +180, and 1-year post hematopoietic cell transplant.

Time frame:
Days +28, +42, +60, +100, +180, and 1-year post hematopoietic cell transplant
Reported as:
Median · percentage T-cells
Percentage of Donor T-cell Populations at Days +28, +42, +60, +100, +180, and 1-year Post Hematopoietic Cell Transplant (HCT)
percentage T-cellsReduced Intensity Conditioning+Allogeneic Hematopoietic Cell Transplant + Graft-versus-Host DiseaseImmunosuppression-Only Conditioning + Allo Hematopoietic Cell Transplant +Graft-versus-Host Disease
Day +28 after HCT91 (9 to 100)95 (95 to 95)
Day +42 after HCT97 (0 to 100)99.5 (99 to 100)
Day +60 after HCT97.5 (0 to 100)98 (0 to 100)
Day +100 after HCT98 (56 to 100)98 (98 to 100)
Day +180 after HCT100 (67 to 100)100 (100 to 100)
Day +365 after HCT100 (79 to 100)90 (90 to 90)
SecondaryCumulative Incidence of Chronic Graft-versus-host Disease (cGVHD)

Cumulative incidence curves of chronic graft versus host disease and two-sided 95% confidence intervals at 1 and 2-years post -transplant. cGVHD was scored according to the 2014 National Institutes of Health (NIH) Consensus Criteria for Clinical Trials in Chronic GVHD. Eight organs will be scored on a 0-3 scale.

Time frame:
1 and 2-years post-transplant

Results for this outcome have not been posted.

SecondaryCumulative Incidence of Acute Graft-versus-host Disease (aGVHD) at 1 Year

Cumulative incidence curves of acute graft versus host disease and two-sided 95% confidence intervals at 1-year post transplant according to Keystone Criteria of the 1994 Consensus Conference on Acute GVHD Grading. Acute GVHD is defined as any grade, grade 2, 3, or 4 and grade 3-4 acute GVHD. The Keystone criteria provide the basis for grading acute GVHD as follows: Organ-Specific Staging: Each affected organ (skin, liver, gut) is staged 0 (absent) to 4 (severe). Overall Grading (I-IV): Based on the most severe organ involvement. Skin (Grade 0-4): Based on % body surface area (BSA) involvement (e.g., \<25% for Grade 1, \>50% for Grade 3, bullae for Grade 4). Liver (Grade 0-4): Based on total serum bilirubin levels (e.g., 2-2.9 mg/dL for Grade 1, \>15 mg/dL for Grade 4). Gut (Grade 0-4): Based on diarrhea volume and severity (e.g., \>500 mL/day for Grade 1, \>2000 mL/day or ileus/severe pain for Grade 4). Upper GI: Included for classification, with specific criteria for staging.

Time frame:
1-year post-transplant
Reported as:
Number · percentage
Cumulative Incidence of Acute Graft-versus-host Disease (aGVHD) at 1 Year
percentageReduced Intensity Conditioning+Allogeneic Hematopoietic Cell Transplant + Graft-versus-Host DiseaseImmunosuppression-Only Conditioning + Allo Hematopoietic Cell Transplant +Graft-versus-Host Disease
Cumulative Incidence of Acute Graft-versus-host Disease (aGVHD) at 1 Year32 (15.2 to 50.2)50 (5.8 to 84.5)
SecondaryPercent Probability Event-free Survival (EFS)

EFS is defined as the time from transplant to death of any cause or other event, including disease relapse, graft failure, grade 3-4 acute graft versus host disease (GVHD), chronic GVHD requiring systemic therapy, or receipt of post-transplant donor cell infusion.

Time frame:
1, 3, and 5-years post-transplant

Results for this outcome have not been posted.

SecondaryCumulative Incidence of Primary Graft Failure at Day +60

Primary graft failure at day +60 estimated using cumulative incidence curves and 95% two-sided confidence intervals. Primary graft failure is defined as \< 5% donor myeloid chimerism in blood and/or bone marrow on all evaluations up to and including day +60, in the absence of a recurrent marrow malignancy.

Time frame:
Day +60
Reported as:
Number · percentage
Cumulative Incidence of Primary Graft Failure at Day +60
percentageReduced Intensity Conditioning+Allogeneic Hematopoietic Cell Transplant + Graft-versus-Host DiseaseImmunosuppression-Only Conditioning + Allo Hematopoietic Cell Transplant +Graft-versus-Host Disease
Cumulative Incidence of Primary Graft Failure at Day +600 (0 to 0)50 (15.5 to 94.2)
SecondaryPercentage of Participants With Lymphoproliferative Disease/Lymphoma Relapse at 1, 3, and 5-years Post-hematopoietic Cell Transplant (HCT)

Lymphoproliferative disease/lymphoma relapse at 1, 3, and 5-years post-HCT estimated using cumulative incidence curves and two-sided 95% confidence intervals at each timepoint.

Time frame:
1, 3, and 5 years post-HCT

Results for this outcome have not been posted.

SecondaryPercent Probability Graft Versus Host Disease (GVHD)-Free Graft Failure-free Survival (GGFS)

Probabilities of GGFS were estimated using the Kaplan-Meier method. GGFS is

Time frame:
1, 3, and 5 years post-hematopoietic cell transplant (HCT)

Results for this outcome have not been posted.

SecondaryPercent Probability of Graft Versus Host Disease (GVHD)-Free Relapse-free Survival (GRFS)

GRFS was estimated using the Kaplan-Meier method. Relapse free survival is

Time frame:
1, 3 and 5-years post-hematopoietic cell transplant (HCT)

Results for this outcome have not been posted.

SecondaryCumulative Incidences of Cytomegalovirus (CMV), BK Virus (BK), Adenovirus, Human Herpes Virus 6 (HHV6), JC Virus (JCV), and Epstein-Barr Virus (EBV) Detection in Blood at Day +100 Post-HCT

Cumulative incidences of CMV, BK, adenovirus, HHV6, JCV, and EBV detection in blood at day +100 post-HCT estimated using cumulative incidence curves along with two-sided 95% confidence intervals.

Time frame:
day +100 post-HCT
Reported as:
Number · percent
Cumulative Incidences of Cytomegalovirus (CMV), BK Virus (BK), Adenovirus, Human Herpes Virus 6 (HHV6), JC Virus (JCV), and Epstein-Barr Virus (EBV) Detection in Blood at Day +100 Post-HCT
percentReduced Intensity Conditioning+Allogeneic Hematopoietic Cell Transplant + Graft-versus-Host DiseaseImmunosuppression-Only Conditioning + Allo Hematopoietic Cell Transplant +Graft-versus-Host Disease
CMV44 (27.3 to 65.2)25 (3.95 to 87.2)
BK64 (45.8 to 81.8)100 (0 to 100)
Adenovirus8 (2.06 to 28.4)75 (33.5 to 99.1)
HHV657.5 (39.2 to 77.1)75 (33.5 to 99.1)
JCV32 (17.5 to 53.9)75 (33.5 to 99.1)
EBV60 (41.9 to 78.7)25 (3.95 to 87.2)
SecondaryPercentage of Donor B-cell Populations at Days +28, +42, +60, +100, +180, and 1-year Post-transplant

The percentage of donor B-cell populations at days +28, +42, +60, +100, +180, and 1-year post-transplant.

Time frame:
Days +28, +42, +60, +100, +180, and 1-year post-transplant

Results for this outcome have not been posted.

SecondaryPercentage of Donor Natural Killer (NK-) Cell Populations at Days +28, +42, +60, +100, +180, and 1-year Post Transplant

Percentage of donor natural killer (NK-) cell populations at days +28, +42, +60, +100, +180, and 1-year post transplant.

Time frame:
Days +28, +42, +60, +100, +180, and 1-year post transplant

Results for this outcome have not been posted.

SecondaryPercentage of Donor Myeloid Cell Populations at Days +28, +42, +60, +100, +180, and 1-year Post Transplant

Percentage of donor myeloid cell populations at days +28, +42, +60, +100, +180, and 1-year post transplant.

Time frame:
Days +28, +42, +60, +100, +180, and 1-year post transplant
Reported as:
Median · percentage cells
Percentage of Donor Myeloid Cell Populations at Days +28, +42, +60, +100, +180, and 1-year Post Transplant
percentage cellsReduced Intensity Conditioning+Allogeneic Hematopoietic Cell Transplant + Graft-versus-Host DiseaseImmunosuppression-Only Conditioning + Allo Hematopoietic Cell Transplant +Graft-versus-Host Disease
Day +28 post-transplant100 (78 to 100)23 (4 to 42)
Day +42 post-transplant100 (61 to 100)4 (0 to 33)
Day +60 post-transplant100 (34 to 100)3 (0 to 29)
Day +100 post-transplant100 (56 to 100)31 (12 to 50)
Day 180 post-transplant100 (67 to 100)22 (22 to 22)
1-year post-transplant100 (92 to 100)33 (33 to 33)
Other pre-specifiedNumber of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Time frame:
Conditioning start until return to baseline/stabilization, 30 days post-therapy end, removal from therapy, or off study, whichever comes first for all AEs, followed by AE collection per principal investigator discretion, on average 2 years.
Reported as:
Count of participants · Participants
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
ParticipantsReduced Intensity Conditioning+Allogeneic Hematopoietic Cell Transplant + Graft-versus-Host DiseaseImmunosuppression-Only Conditioning + Allo Hematopoietic Cell Transplant +Graft-versus-Host Disease7-8/8 Human Leukocyte Antigen (HLA)-Matched Related or Unrelated, or HLA-haploidentical Donor
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)2541

Adverse events

Collected over For Arms 1 and 2, recipients, All-Cause Mortality was monitored/assessed, an average of 2 years. All Adverse Events (AEs) were monitored/assessed from the start of conditioning (hematopoietic cell transplant day -14) until return to baseline or stabilization of event, through 30 days after end of therapy, removal from protocol therapy, or until off study, whichever comes first, followed by collection of AEs per principal investigator discretion, an average of 2 years.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Reduced Intensity Conditioning+Allogeneic Hematopoietic Cell Transplant + Graft-versus-Host Disease4/25 (16%)18/25 (72%)25/25 (100%)
Immunosuppression-Only Conditioning + Allo Hematopoietic Cell Transplant +Graft-versus-Host Disease2/4 (50%)4/4 (100%)4/4 (100%)
7-8/8 Human Leukocyte Antigen (HLA)-Matched Related or Unrelated, or HLA-haploidentical Donor1/10 (10%)0/10 (0%)1/10 (10%)
Most frequent serious events
Showing 10 of 86
Most frequent serious events
EventReduced Intensity Conditioning+Allogeneic Hematopoietic Cell Transplant + Graft-versus-Host DiseaseImmunosuppression-Only Conditioning + Allo Hematopoietic Cell Transplant +Graft-versus-Host Disease7-8/8 Human Leukocyte Antigen (HLA)-Matched Related or Unrelated, or HLA-haploidentical Donor
HypotensionVascular disorders1/252/40/10
HypoxiaRespiratory, thoracic and mediastinal disorders1/252/40/10
Platelet count decreasedInvestigations11/250/40/10
Neutrophil count decreasedInvestigations10/251/40/10
White blood cell decreasedInvestigations7/251/40/10
Abdominal painGastrointestinal disorders0/251/40/10
Acute kidney injuryRenal and urinary disorders1/251/40/10
AscitesGastrointestinal disorders0/251/40/10
BacteremiaInfections and infestations5/251/40/10
Creatinine increasedInvestigations1/251/40/10
Most frequent other events
Showing 10 of 165
Most frequent other events
EventReduced Intensity Conditioning+Allogeneic Hematopoietic Cell Transplant + Graft-versus-Host DiseaseImmunosuppression-Only Conditioning + Allo Hematopoietic Cell Transplant +Graft-versus-Host Disease7-8/8 Human Leukocyte Antigen (HLA)-Matched Related or Unrelated, or HLA-haploidentical Donor
White blood cell decreasedInvestigations19/254/40/10
Neutrophil count decreasedInvestigations19/252/40/10
Infusion related reactionInjury, poisoning and procedural complications9/253/40/10
AnemiaBlood and lymphatic system disorders18/252/40/10
Platelet count decreasedInvestigations18/251/40/10
HypokalemiaMetabolism and nutrition disorders15/251/40/10
NauseaGastrointestinal disorders15/251/40/10
Mucositis oralGastrointestinal disorders13/250/40/10
AnorexiaMetabolism and nutrition disorders4/252/40/10
HypoalbuminemiaMetabolism and nutrition disorders4/252/40/10

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Reduced Intensity Conditioning+Allogeneic Hematopoietic Cell Transplant + Graft-versus-Host DiseaseImmunosuppression-Only Conditioning + Allo Hematopoietic Cell Transplant +Graft-versus-Host Disease7-8/8 Human Leukocyte Antigen (HLA)-Matched Related or Unrelated, or HLA-haploidentical DonorParticipants Enrolled But Not TreatedNational Marrow Donor Program (NMDP) DonorsTotal
<=18 years7008—15
Between 18 and 65 years184912—43
>=65 years0010—1
Age, Continuous
Age, Continuous(years)Reduced Intensity Conditioning+Allogeneic Hematopoietic Cell Transplant + Graft-versus-Host DiseaseImmunosuppression-Only Conditioning + Allo Hematopoietic Cell Transplant +Graft-versus-Host Disease7-8/8 Human Leukocyte Antigen (HLA)-Matched Related or Unrelated, or HLA-haploidentical DonorParticipants Enrolled But Not TreatedNational Marrow Donor Program (NMDP) DonorsTotal
Mean26.04 ± 15.132 ± 12.1135.5 ± 16.1626.35 ± 14.45—28.15 ± 14.97
Sex: Female, Male
Sex: Female, Male(Participants)Reduced Intensity Conditioning+Allogeneic Hematopoietic Cell Transplant + Graft-versus-Host DiseaseImmunosuppression-Only Conditioning + Allo Hematopoietic Cell Transplant +Graft-versus-Host Disease7-8/8 Human Leukocyte Antigen (HLA)-Matched Related or Unrelated, or HLA-haploidentical DonorParticipants Enrolled But Not TreatedNational Marrow Donor Program (NMDP) DonorsTotal
Female11137426
Male143713845
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Reduced Intensity Conditioning+Allogeneic Hematopoietic Cell Transplant + Graft-versus-Host DiseaseImmunosuppression-Only Conditioning + Allo Hematopoietic Cell Transplant +Graft-versus-Host Disease7-8/8 Human Leukocyte Antigen (HLA)-Matched Related or Unrelated, or HLA-haploidentical DonorParticipants Enrolled But Not TreatedNational Marrow Donor Program (NMDP) DonorsTotal
Ethnicity - Hispanic or Latino7032—12
Ethnicity - Not Hispanic or Latino174517—43
Ethnicity - Unknown or Not Reported1021—4
Race - American Indian or Alaska Native0000—0
Race - Asian1012—4
Race - Native Hawaiian or Other Pacific Islander0000—0
Race - Black or African American1103—5
Race - White203613—42
Race - More Than One Race1000—1
Race - Unknown or Not Reported2021—5
Race - Other0010—1
Race - Asian White0001—1
Region of Enrollment
Region of Enrollment(participants)Reduced Intensity Conditioning+Allogeneic Hematopoietic Cell Transplant + Graft-versus-Host DiseaseImmunosuppression-Only Conditioning + Allo Hematopoietic Cell Transplant +Graft-versus-Host Disease7-8/8 Human Leukocyte Antigen (HLA)-Matched Related or Unrelated, or HLA-haploidentical DonorParticipants Enrolled But Not TreatedNational Marrow Donor Program (NMDP) DonorsTotal
United States25410201271
07

Study locations

2 sites
  • National Institutes of Health Clinical Center
    Bethesda, Maryland 20892, United States
  • National Marrow Donor Program
    Minneapolis, Minnesota 55401, United States
08

References and documents

Publications

  • Dimitrova D, et al. BK virus-associated hemorrhagic cystitis in posttransplant cyclophosphamide-based allogeneic hematopoietic cell transplantation (HCT) for immune deficiency or dysregulation. The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation; Glasgow, United Kingdom; April 16, 2024.
  • Cusmano A, Soldatos A, Notarangelo L, Grimes A, Makkeyah S, Selim L, Kanakry J, Dimitrova D. Allogeneic hematopoietic cell transplantation (HCT) in two pediatric patients with central nervous system-restricted familial hemophagocytic lymphohistiocytosis. The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation; Glasgow, United Kingdom; April 15, 2024. (presenting and senior author)
  • Cusmano A, Maher J, Gomez-Lobo V, Freeman A, Uzel G, Kanakry JA, Dimitrova D. Ovarian function following reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT): how fertile is the future? Transplantation and Cellular Therapy Meetings of ASTCT and CIBMTR; San Antonio, TX; February 22, 2024. (presenting and senior author)
  • Dimitrova D, et al. Pre-Transplant Anti-CD20 Monoclonal Antibody Therapy Affects the Donor-Derived Hematopoietic Compartment in Allogeneic Hematopoietic Cell Transplantation (HCT) Recipients. The 49th Annual Meeting of the European Society for Blood and Marrow Transplantation; Paris, France; April 23-26, 2023.
  • Dimitrova D, et al. Humoral Reconstitution after Allogeneic Hematopoietic Cell Transplantation (HCT) in Patients Pretreated with Targeted Anti-CD20 Therapy. Transplantation and Cellular Therapy Meetings of ASTCT and CIBMTR; Orlando, FL; February 16, 2023.
  • Dimitrova D, Napier S, Stokes A, Uzel G, Miljkovic M, Pittaluga S, Wang H, Notarangelo LD, Ombrello AK, Stone D, Cuellar-Rodriguez J, Wilder J, Hicks SN, Sadler JL, Fowler DH, Gress RE, Kanakry CG, Kanakry JA. Distal Equine Anti-Thymocyte Globulin (ATG) As an Adjunct to Reduced Intensity Conditioning and Posttransplantation Cyclophosphamide (PTCy) for Allogeneic Hematopoietic Cell Transplantation (HCT) in Patients with Benign and Malignant Disorders of T Cell Proliferation or Dysregulation. Transplantation and Cellular Therapy Meetings of ASTCT and CIBMTR; virtual; February 8-12, 2021.
  • Dimitrova D, Uzel G, Notarangelo LD, Ombrello AK, Stone D, Parta M, Carroll E, Wilder J, Hicks SN, Sadler JL, Fowler DH, Gress RE, Kanakry CG, Kanakry JA. Novel Reduced Intensity Conditioning (RIC) Approach to Allogeneic Hematopoietic Cell Transplantation (HCT) in Patients with Benign and Malignant Disorders of T Cell Proliferation or Dysregulation. The 46th Annual Meeting of the European Society for Blood and Marrow Transplantation; virtual; August 2020.
  • Rechache, Kamil & Dimitrova, Dimana & Feng, Xingmin & Flomerfelt, Francis & Napier, Scott & Sponaugle, Jennifer & Stokes, Anita & Hyder, Mustafa & McKeown, Christi & Wilder, Jennifer & Baruffaldi, Judy & Chai, Amy & Walker, Melissa & Gress, Ronald & Kanakry, Christopher & Kanakry, Jennifer. (2022). Distally-Timed Equine Antithymocyte Globulin (eATG) in Allogeneic Hematopoietic Cell Transplantation (HCT) Conditioning - Pharmacokinetics and the Relationship between Total E-ATG Levels, Pre-HCT Absolute Lymphocyte Count, Immune Reconstitution, and Graft-Versus-Host Responses. Transplantation and Cellular Therapy. 28. S80. 10.1016/S2666-6367(22)00254-8.
  • Kamil A. Rechache, Natalia S. Nunes, Xingmin Feng, Francis A Flomerfelt, William Telford, Brian Dawson, Thomas E. Hughes, Syed Muhammad Salman Shah, Jennifer Sponaugle, Amy Chai, Jessenia Campos, Mustafa A. Hyder, Dimana Dimitrova, Christopher G. Kanakry, Jennifer A. Kanakry,The Pharmacokinetics and Pharmacodynamics of Distally-Timed Eatg in Allogeneic Hematopoietic Cell Transplantation Conditioning,Transplantation and Cellular Therapy,Volume 31, Issue 2, Supplement,2025,Pages S174-S175,ISSN 2666-6367,https://doi.org/10.1016/j.jtct.2025.01.269.
  • Xue E, Das S, Choo-Wosoba H, Dimitrova D, Hyder MA, Flomerfelt FA, Dawson B, Telford W, Upadhyaya KD, Rechache K, Kanakry CG, Kanakry JA. Frequency, kinetics, and clinical significance of HHV-6 DNAemia after PTCy-based hematopoietic cell transplant. Blood Adv. 2026 Jul 17:bloodadvances.2025018166. doi: 10.1182/bloodadvances.2025018166. Online ahead of print. PubMed 42469162 ↗

Study documents

  • Protocol and statistical analysis plan · Aug 29, 2024
  • Informed consent form · Jul 16, 2024
  • Informed consent form · Jul 16, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).

Supporting information: Study protocol, Sap, Icf

09

Registry details

Key details

Study ID
NCT03663933
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Dimana Dimitrova (Principal Investigator, National Cancer Institute (NCI)) — Principal investigator
First posted
Sep 10, 2018
Start date
Sep 4, 2018
Primary completion
Apr 3, 2025
Completion
Apr 3, 2030 (estimated)
Results posted
Mar 17, 2026
Last update
Mar 17, 2026

Study contacts

Dimana Dimitrova, M.D.
principal investigator · National Cancer Institute (NCI)

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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