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

February 26, 2026 updated by: Dimana Dimitrova, National Cancer Institute (NCI)

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
71

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

4 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm 1/Reduced-Intensity Conditioning (RIC)
Reduced Intensity Conditioning Arm.
Procedure: Allogeneic HSC
Stem cell transplant
Other Names:
  • Allogeneic hematopoietic stem cell (HSC)
Diagnostic test: EKG
Baseline
Other Names:
  • Electrocardiogram
Drug: e-ATG
During Immunosuppression Only Conditioning (IOC) and Reduced Intensity Conditioning (RIC).
Other Names:
  • Atgam
  • Antithymocyte Globulin (Equine)
Procedure: Immunosuppression 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.
Other Names:
  • IOC
Procedure: Reduced 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.
Other Names:
  • RIC
Drug: GVHD 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.
Other Names:
  • Graft-versus-host disease prophylaxis
Drug: Bisulfan
During Reduced Intensity Conditioning (RIC).
Other Names:
  • Busulfex
  • Myleran
Drug: Prednisone
During Immunosuppression Only Conditioning (IOC) and Reduced Intensity Conditioning (RIC).
Other Names:
  • Deltasone
Drug: Cyclophosphamide
During Immunosuppression Only Conditioning (IOC), Reduced Intensity Conditioning (RIC) and Graft-versus-host disease prophylaxis (GVHD).
Other Names:
  • Cytoxan
  • Neosar
Drug: MMF
During Graft-versus-host disease prophylaxis (GVHD).
Other Names:
  • CellCept
  • Mycophenolate mofetil
Drug: Mesna
During Graft-versus-host disease prophylaxis (GVHD).
Other Names:
  • Mesnex
  • Uromitexan
Drug: Tacrolimus
During Graft-versus-host disease prophylaxis (GVHD).
Other Names:
  • Prograf
Drug: Pentostatin
During Immunosuppression Only Conditioning (IOC) and Reduced Intensity Conditioning (RIC).
Other Names:
  • Nipent
  • Deoxycoformycin
Diagnostic test: PFTs
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).
Other Names:
  • Pulmonary function tests
Diagnostic test: DEXA
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).
Other Names:
  • Dual-energy x-ray absorptiometry
Procedure: Bone Marrow Aspirate & Biopsy
Baseline, Day +60 (± 3 days) and Day +365 (±21 days).
Other Names:
  • BM aspirate & bx
Diagnostic test: 2D 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).
Other Names:
  • 2-dimensional echocardiogram
Experimental: Arm 2/Immunosuppression-only Conditioning (IOC)
Immunosuppression Only Conditioning Arm.
Procedure: Allogeneic HSC
Stem cell transplant
Other Names:
  • Allogeneic hematopoietic stem cell (HSC)
Diagnostic test: EKG
Baseline
Other Names:
  • Electrocardiogram
Drug: e-ATG
During Immunosuppression Only Conditioning (IOC) and Reduced Intensity Conditioning (RIC).
Other Names:
  • Atgam
  • Antithymocyte Globulin (Equine)
Procedure: Immunosuppression 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.
Other Names:
  • IOC
Drug: GVHD 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.
Other Names:
  • Graft-versus-host disease prophylaxis
Drug: Bisulfan
During Reduced Intensity Conditioning (RIC).
Other Names:
  • Busulfex
  • Myleran
Drug: Prednisone
During Immunosuppression Only Conditioning (IOC) and Reduced Intensity Conditioning (RIC).
Other Names:
  • Deltasone
Drug: Cyclophosphamide
During Immunosuppression Only Conditioning (IOC), Reduced Intensity Conditioning (RIC) and Graft-versus-host disease prophylaxis (GVHD).
Other Names:
  • Cytoxan
  • Neosar
Drug: MMF
During Graft-versus-host disease prophylaxis (GVHD).
Other Names:
  • CellCept
  • Mycophenolate mofetil
Drug: Mesna
During Graft-versus-host disease prophylaxis (GVHD).
Other Names:
  • Mesnex
  • Uromitexan
Drug: Tacrolimus
During Graft-versus-host disease prophylaxis (GVHD).
Other Names:
  • Prograf
Drug: Pentostatin
During Immunosuppression Only Conditioning (IOC) and Reduced Intensity Conditioning (RIC).
Other Names:
  • Nipent
  • Deoxycoformycin
Diagnostic test: PFTs
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).
Other Names:
  • Pulmonary function tests
Diagnostic test: DEXA
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).
Other Names:
  • Dual-energy x-ray absorptiometry
Procedure: Bone Marrow Aspirate & Biopsy
Baseline, Day +60 (± 3 days) and Day +365 (±21 days).
Other Names:
  • BM aspirate & bx
Diagnostic test: 2D 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).
Other Names:
  • 2-dimensional echocardiogram
No Intervention: Arm 3/Donor
Healthy Donor- Donors for recipients in arm 1 or arm 2.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Time Frame: Day +180 post-HCT
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.
Day +180 post-HCT
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
Time Frame: Day +180 post -HCT
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.
Day +180 post -HCT

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Cumulative Incidence of Transplant-related Mortality
Time Frame: Day +180, and 1-year post-transplant
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.
Day +180, and 1-year post-transplant
Cumulative Incidence of Secondary Graft Failure
Time Frame: 1-, 3-, and 5-years post-transplant
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).
1-, 3-, and 5-years post-transplant
Percent Probability of Overall Survival (OS)
Time Frame: 1-, 3-, and 5-years post-transplant
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.
1-, 3-, and 5-years post-transplant
Percentage of Participants Who Achieve Chimerism at Stated Days Between Those Who Have Failed by Day 60 or Have Not
Time Frame: Day +21, +28, +35, +42, and +60 after hematopoietic cell transplant (HCT)

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.
Day +21, +28, +35, +42, and +60 after hematopoietic cell transplant (HCT)
Percentage of Donor T-cell Populations at Days +28, +42, +60, +100, +180, and 1-year Post Hematopoietic Cell Transplant (HCT)
Time Frame: Days +28, +42, +60, +100, +180, and 1-year post hematopoietic cell transplant
The percentage of donor T-cell populations at days +28, +42, +60, +100, +180, and 1-year post hematopoietic cell transplant.
Days +28, +42, +60, +100, +180, and 1-year post hematopoietic cell transplant
Cumulative Incidence of Chronic Graft-versus-host Disease (cGVHD)
Time Frame: 1 and 2-years post-transplant
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.
1 and 2-years post-transplant
Cumulative Incidence of Acute Graft-versus-host Disease (aGVHD) at 1 Year
Time Frame: 1-year post-transplant
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.
1-year post-transplant
Percent Probability Event-free Survival (EFS)
Time Frame: 1, 3, and 5-years post-transplant
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.
1, 3, and 5-years post-transplant
Cumulative Incidence of Primary Graft Failure at Day +60
Time Frame: 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.
Day +60
Percentage of Participants With Lymphoproliferative Disease/Lymphoma Relapse at 1, 3, and 5-years Post-hematopoietic Cell Transplant (HCT)
Time Frame: 1, 3, and 5 years post-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.
1, 3, and 5 years post-HCT
Percent Probability Graft Versus Host Disease (GVHD)-Free Graft Failure-free Survival (GGFS)
Time Frame: 1, 3, and 5 years post-hematopoietic cell transplant (HCT)
Probabilities of GGFS were estimated using the Kaplan-Meier method. GGFS is
1, 3, and 5 years post-hematopoietic cell transplant (HCT)
Percent Probability of Graft Versus Host Disease (GVHD)-Free Relapse-free Survival (GRFS)
Time Frame: 1, 3 and 5-years post-hematopoietic cell transplant (HCT)
GRFS was estimated using the Kaplan-Meier method. Relapse free survival is
1, 3 and 5-years post-hematopoietic cell transplant (HCT)
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
Time Frame: 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.
day +100 post-HCT
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
The percentage of donor B-cell populations at days +28, +42, +60, +100, +180, and 1-year post-transplant.
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
Percentage of donor natural killer (NK-) cell populations at days +28, +42, +60, +100, +180, and 1-year post transplant.
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
Percentage of donor myeloid cell populations at days +28, +42, +60, +100, +180, and 1-year post transplant.
Days +28, +42, +60, +100, +180, and 1-year post transplant

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
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.
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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Dimana Dimitrova, M.D., National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General 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.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 4, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 3, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 3, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 7, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 7, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 10, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 17, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 26, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 180135
  • 18-C-0135

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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).

IPD Sharing Time Frame

Clinical data available during the study and indefinitely. Genomic data is available once genomic data is uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.

IPD Sharing Access Criteria

Clinical data will be made available with the permission of the study principal investigator (PI). Genomic data is made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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