AzTrials
AzTrials

Lymphoproliferative DisordersPhase 2NCT03663933

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

A Phase 2 study testing e-ATG, Immunosuppression Only Conditioning and Reduced Intensity Conditioning in people with Lymphoproliferative Disorders and Autoimmune Lymphoproliferative, run by National Cancer Institute (NCI) at 2 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 4 years and olderHealthy volunteers can take part
What is being tested?
e-ATG, Immunosuppression Only Conditioning and Reduced Intensity Conditioning
Could I receive a placebo?
No, everyone receives an active treatment
How many people
71 participants
Where
2 sitesUnited States
Study dates
4 Sep 2018to 3 Apr 2030
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 4 years and older
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult, Older adult

Who may be able to join

  • 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
Show all 25Show fewer
  • 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.
  • 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.
  • -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.

Who cannot join

  • 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
  • -None
  • -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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

  • National Marrow Donor Program

    Minneapolis, Minnesota, 55401

Other trials in United States

About this study

Official title: 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.

Read more

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.
Being tested
e-ATG, Immunosuppression Only Conditioning, Reduced Intensity Conditioning, GVHD Prophylaxis, Allogeneic HSC
Keywords
Haploidentical, Autoimmunity, Immune Dysregulation, Congenital, Opportunistic Infection
Medical subject headings
Lymphoproliferative Disorders, T cell immunodeficiency primary, Immune System Diseases, Common Variable Immunodeficiency, Autoimmune Diseases, Opportunistic Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • e-ATGDrug

    Also called Antithymocyte Globulin (Equine), Atgam

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

  • Immunosuppression Only ConditioningProcedure or surgery

    Also called IOC

    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.

  • Reduced Intensity ConditioningProcedure or surgery

    Also called RIC

    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.

  • GVHD ProphylaxisDrug

    Also called Graft-versus-host disease 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.

  • Allogeneic HSCProcedure or surgery

    Also called Allogeneic hematopoietic stem cell (HSC)

    Stem cell transplant

  • BisulfanDrug

    Also called Busulfex, Myleran

    During Reduced Intensity Conditioning (RIC).

  • PrednisoneDrug

    Also called Deltasone

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

  • CyclophosphamideDrug

    Also called Cytoxan, Neosar

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

  • MMFDrug

    Also called Mycophenolate mofetil, CellCept

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

  • MesnaDrug

    Also called Mesnex, Uromitexan

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

  • TacrolimusDrug

    Also called Prograf

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

  • PentostatinDrug

    Also called Nipent, Deoxycoformycin

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

  • PFTsDiagnostic test

    Also called Pulmonary function tests

    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).

  • DEXADiagnostic test

    Also called Dual-energy x-ray absorptiometry

    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).

  • Bone Marrow Aspirate & BiopsyProcedure or surgery

    Also called BM aspirate & bx

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

  • EKGDiagnostic test

    Also called Electrocardiogram

    Baseline

  • 2D ECHODiagnostic test

    Also called 2-dimensional echocardiogram

    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).

Study groups in NCT03663933
Study groupRoleWhat they receive
Arm 1/Reduced-Intensity Conditioning (RIC)ExperimentalReduced Intensity Conditioning Arm.
Receives: 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
Arm 2/Immunosuppression-only Conditioning (IOC)ExperimentalImmunosuppression Only Conditioning Arm.
Receives: 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
Arm 3/DonorNo interventionHealthy Donor- Donors for recipients in arm 1 or arm 2.

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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.

    Measured: Day +180 post -HCT

Secondary outcomes (16)

  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.

    Measured: 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).

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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

    Measured: 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

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Sep 2018
  2. Study start4 Sep 2018
  3. Primary completion3 Apr 2025
  4. Study completion3 Apr 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
71 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03663933
Sponsor's protocol ID
180135
Other IDs
18-C-0135
Status last verified
Feb 2026
First submitted
7 Sep 2018
Last updated
17 Mar 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
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).

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.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing e-ATG, Immunosuppression Only Conditioning and Reduced Intensity Conditioning in people with Lymphoproliferative Disorders and Autoimmune Lymphoproliferative, run by National Cancer Institute (NCI) at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 17 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03663933, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2026.

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