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NCT02220985 · REGISTRY CONDITION SEARCH

Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors in Preventing GVHD

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE2
Status at capture
COMPLETED
Registry last update
2026-06-01

This phase II trial is for patients with acute lymphocytic leukemia, acute myeloid leukemia, myelodysplastic syndrome or chronic myeloid leukemia who have been referred for a peripheral blood stem cell transplantation to treat their cancer. In these transplants, chemotherapy and total-body radiotherapy ('conditioning') are used to kill residual leukemia cells and the patient's normal blood cells, especially immune cells that could reject the donor cells. Following the chemo/radiotherapy, blood stem cells from the donor are infused. These stem cells will grow and eventually replace the patient's original blood system, including red cells that carry oxygen to our tissues, platelets that stop bleeding from damaged vessels, and multiple types of immune-system white blood cells that fight infections. Mature donor immune cells, especially a type of immune cell called T lymphocytes (or T cells) are transferred along with these blood-forming stem cells. T cells are a major part of the curative power of transplantation because they can attack leukemia cells that have survived the chemo/radiation therapy and also help to fight infections after transplantation. However, donor T cells can also attack a patient's healthy tissues in an often-dangerous condition known as Graft-Versus-Host-Disease (GVHD). Drugs that suppress immune cells are used to decrease the severity of GVHD; however, they are incompletely effective and prolonged immunosuppression used to prevent and treat GVHD significantly increases the risk of serious infections. Removing all donor T cells from the transplant graft can prevent GVHD, but doing so also profoundly delays infection-fighting immune reconstitution and eliminates the possibility that donor immune cells will kill residual leukemia cells. Work in animal models found that depleting a type of T cell, called naïve T cells or T cells that have never responded to an infection, can diminish GVHD while at least in part preserving some of the benefits of donor T cells including resistance to infection and the ability to kill leukemia cells. This clinical trial studies how well the selective removal of naïve T cells works in preventing GVHD after peripheral blood stem cell transplants. This study will include patients conditioned with high or medium intensity chemo/radiotherapy who can receive donor grafts from related or unrelated donors.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Chronic GVHD

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outcome · NOT POSTED

Other Immunosuppressive Agents

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outcome · POSTED

Time to Completion of Prednisone

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outcome · POSTED

Time to Completion of All Immunosuppression

→

outcome · POSTED

Requirement of Immunosuppression at 2 Years After Transplant

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outcome · POSTED

Acute GVHD

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outcome · NOT POSTED

aGVHD Management - Secondary

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outcome · POSTED

Graft Failure

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outcome · POSTED

Transplant Related Mortality by Day 100

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outcome · POSTED

Relapse

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outcome · POSTED

Engraftment - ANC >500/uL

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outcome · POSTED

Engraftment - ANC <1,000/uL

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outcome · POSTED

Platelet Engraftment

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outcome · POSTED

Platelet Engraftment - 50,000/uL

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outcome · NOT POSTED

Chimerism Analysis

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

→
Who could take part
eligibility Criteria
Inclusion Criteria: * Patients who are considered appropriate candidates for allogeneic hematopoietic stem cell transplantation and have one of the following diagnoses: * Acute lymphocytic leukemia in first or subsequent remission * Acute myeloid leukemia in first or subsequent remission * Acute lymphocytic leukemia in relapse or primary refractory disease with a circulating blast count of no more than 10,000/mm\^3 (Arms A or C only) * Acute myeloid leukemia in relapse or primary refractory disease with a circulating blast count of no more than 10,000/mm\^3 (Arms A or C only) * Refractory anemia with excess blasts (RAEB-1 and RAEB-2) (if the patient has received previous induction chemotherapy within 60 days) * Chronic myelogenous leukemia with a history of accelerated phase or blast crisis (if the patient has received at least one course of induction chemotherapy) * Other acute leukemia or related neoplasm (including but not limited to 'biphenotypic', 'undifferentiated' or 'ambiguous lineage' acute leukemia, blastic plasmacytoid dendritic cell neoplasm or lymphoblastic lymphoma) * Patients 0-49 years old will be enrolled in Arm A or C (high-intensity) * Patients 50-60 years old will be enrolled in Arm B or D (lower intensity); patients eligible for Arms B or D also include those who have received previous allogeneic HCT, or who have co-morbid conditions rendering them unsuitable for high-dose conditioning, determined in consultation with the principal investigator * Patient with a HLA-matched (HLA-A, B, C, and DR beta 1 \[DRB1\] molecularly matched) unrelated donor or related donor capable of donating PBSC * DONOR INCLUSION: * HLA-matched related donors \>= 18 years and capable and willing to donate PBSC (Arms A and B) * HLA-matched unrelated donors (HLA-A, B, C, and DRB1 matched based on high-resolution typing) capable and willing to donate PBSC (Arms C and D) Exclusion Criteria: * Patients with central nervous system (CNS) involvement refractory to intrathecal chemotherapy and/or standard cranial-spinal radiation * Patients on other experimental protocols for prevention of acute GVHD * Patient weight \>= 100 kg; patients \>= 70 kg with MUDs must be discussed with the principal investigator * Patients who are human immunodeficiency virus positive (HIV+) * Patients with uncontrolled infections for whom myeloablative HCT is considered contraindicated by the consulting infectious disease physician (upper respiratory tract viral infection does not constitute an uncontrolled infection in this context) * Patients with organ dysfunction * ARM A OR C EXCLUSION: * Creatinine \> 1.5 mg/dl at the present time; patients with a known history of creatinine \> 1.5 mg/dl must have a current estimated creatinine clearance of \> 40 ml/min * Cardiac ejection fraction \< 45% * Diffusing capacity of the lung for carbon monoxide (DLCO) corrected \< 60%; patients who are unable to perform pulmonary function tests (for example, due to young age and/or developmental status) will be excluded if the oxygen (O2) saturation is \< 92% on room air * Liver function abnormality; patients who have liver function tests (LFTs) (including total bilirubin, aspartate aminotransferase \[AST\] and alanine aminotransferase \[ALT\]) \>= twice the upper limit of normal should be evaluated by a gastrointestinal (GI) physician; unless there is a clear precipitating factor (such as an azole, methotrexate, Bactrim or another drug); if the GI physician considers that HCT on the high-intensity arms of protocol is contraindicated for that patient the patient may be considered for treatment on the lower intensity arm of the protocol or excluded from the protocol; patients with Gilbert's syndrome and no other known liver function abnormality and patients with reversible drug-related transaminitis do not necessarily require GI consultation and may be included on the high-intensity arms of the protocol * ARM B OR D EXCLUSION: * Creatinine \> 2.0 mg/dl at the present time; patients with a known history of creatinine \> 1.5 mg/dl must have a current estimated creatinine clearance \> 40 ml/min * Cardiac ejection fraction \< 35% * DLCO corrected \< 50%; patients who are unable to perform pulmonary function tests (for example, due to young age and/or developmental status) will be excluded if the O2 saturation is \< 92% on room air; patients with a DLCO 50-60% must also have a partial pressure of oxygen (pO2) of \> 80 mmHg * Liver function abnormality; patients who have LFTs \>= twice the upper limit of normal should be evaluated by a GI physician unless there is a clear precipitating factor (such as an azole, methotrexate, Bactrim or another drug); patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin \> 3 mg/dL, and symptomatic biliary disease will be excluded * Patients will be excluded from Arms A and C if they have received a previous myeloablative transplant; patients who have received a prior HCT at least 6 months prior may be considered for inclusion on Arms B or D after discussion with the principal investigator (PI) * Patients with a life expectancy \< 3 months from co-existing disease other than the leukemia or RAEB * Patients who are pregnant or breast-feeding * Fertile patients of child bearing age unwilling to use contraception during and for 12 months post-transplant * Patients with a significant other medical conditions that would make them unsuitable for transplant * Patients with a known hypersensitivity to tacrolimus, methotrexate (Arm A or C) or MMF (Arm B or D) * DONOR EXCLUSION: * Donors who are HIV-1, HIV-2, human T-lymphotropic virus (HTLV)-1, HTLV-2 seropositive or with active hepatitis B or hepatitis C virus infection * Donors who fail eligibility requirements for donation of cells or tissue for donation of a Human Cell and Tissue Products (HCT/P) will be excluded unless use of the cells complies urgent medical need or allogeneic use in a first-degree or second-degree relative * Unrelated donors donating outside of the United States of America (USA)
healthy Volunteers
true
maximum Age
60 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. description
    HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with GCSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
    intervention Names
    1. Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
    2. Drug: Cyclophosphamide
    3. Drug: Fludarabine Phosphate
    4. Other: Laboratory Biomarker Analysis
    5. Drug: Methotrexate
    6. Procedure: Peripheral Blood Stem Cell Transplantation
    7. Drug: Tacrolimus
    8. Drug: Thiotepa
    9. Radiation: Total-Body Irradiation
    label
    Arm A (MRD)
    type
    EXPERIMENTAL
  2. description
    LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with GCSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator.
    intervention Names
    1. Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
    2. Drug: Cyclophosphamide
    3. Drug: Fludarabine Phosphate
    4. Other: Laboratory Biomarker Analysis
    5. Drug: Mycophenolate Mofetil
    6. Procedure: Peripheral Blood Stem Cell Transplantation
    7. Drug: Tacrolimus
    8. Drug: Thiotepa
    9. Radiation: Total-Body Irradiation
    label
    Arm B (MRD)
    type
    EXPERIMENTAL
  3. description
    HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
    intervention Names
    1. Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
    2. Drug: Cyclophosphamide
    3. Drug: Fludarabine Phosphate
    4. Other: Laboratory Biomarker Analysis
    5. Drug: Methotrexate
    6. Procedure: Peripheral Blood Stem Cell Transplantation
    7. Drug: Tacrolimus
    8. Drug: Thiotepa
    9. Radiation: Total-Body Irradiation
    label
    Arm C (MUD)
    type
    EXPERIMENTAL
  4. description
    LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator.
    intervention Names
    1. Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
    2. Drug: Cyclophosphamide
    3. Drug: Fludarabine Phosphate
    4. Other: Laboratory Biomarker Analysis
    5. Drug: Mycophenolate Mofetil
    6. Procedure: Peripheral Blood Stem Cell Transplantation
    7. Drug: Tacrolimus
    8. Drug: Thiotepa
    label
    Arm D (MUD)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Arm A (MRD)
    2. Arm B (MRD)
    3. Arm C (MUD)
    4. Arm D (MUD)
    description
    Undergo allogeneic HSCT
    name
    Allogeneic Hematopoietic Stem Cell Transplantation
    other Names
    1. Allogeneic Hematopoietic Cell Transplantation
    2. Allogeneic Stem Cell Transplantation
    3. HSC
    4. HSCT
    type
    PROCEDURE
  2. arm Group Labels
    1. Arm A (MRD)
    2. Arm B (MRD)
    3. Arm C (MUD)
    4. Arm D (MUD)
    description
    Given IV
    name
    Cyclophosphamide
    other Names
    1. (-)-Cyclophosphamide
    2. 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
    3. Carloxan
    4. Ciclofosfamida
    5. Ciclofosfamide
    6. Cicloxal
    7. Clafen
    8. Claphene
    9. CP monohydrate
    10. CTX
    11. CYCLO-cell
    12. Cycloblastin
    type
    DRUG
  3. arm Group Labels
    1. Arm A (MRD)
    2. Arm B (MRD)
    3. Arm C (MUD)
    4. Arm D (MUD)
    description
    Given IV
    name
    Fludarabine Phosphate
    other Names
    1. 2-F-ara-AMP
    2. 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
    3. Beneflur
    4. Fludara
    5. SH T 586
    type
    DRUG
  4. arm Group Labels
    1. Arm A (MRD)
    2. Arm B (MRD)
    3. Arm C (MUD)
    4. Arm D (MUD)
    description
    Correlative studies
    name
    Laboratory Biomarker Analysis
    type
    OTHER
  5. arm Group Labels
    1. Arm A (MRD)
    2. Arm C (MUD)
    description
    Given IV
    name
    Methotrexate
    other Names
    1. Abitrexate
    2. Alpha-Methopterin
    3. Amethopterin
    4. Brimexate
    5. CL 14377
    6. CL-14377
    7. Emtexate
    8. Emthexat
    9. Emthexate
    10. Farmitrexat
    11. Fauldexato
    12. Folex
    type
    DRUG
  6. arm Group Labels
    1. Arm B (MRD)
    2. Arm D (MUD)
    description
    Given IV and PO
    name
    Mycophenolate Mofetil
    other Names
    1. Cellcept
    2. MMF
    type
    DRUG
  7. arm Group Labels
    1. Arm A (MRD)
    2. Arm B (MRD)
    3. Arm C (MUD)
    4. Arm D (MUD)
    description
    Undergo PBSCT with GCSF-mobilized CD34-enriched PBSC
    name
    Peripheral Blood Stem Cell Transplantation
    other Names
    1. PBPC transplantation
    2. PBSCT
    3. Peripheral Blood Progenitor Cell Transplantation
    4. Peripheral Stem Cell Support
    5. Peripheral Stem Cell Transplant
    6. Peripheral Stem Cell Transplantation
    type
    PROCEDURE
  8. arm Group Labels
    1. Arm A (MRD)
    2. Arm B (MRD)
    3. Arm C (MUD)
    4. Arm D (MUD)
    description
    Undergo PBSCT with CD45RA-depleted cells
    name
    Peripheral Blood Stem Cell Transplantation
    other Names
    1. PBPC transplantation
    2. PBSCT
    3. Peripheral Blood Progenitor Cell Transplantation
    4. Peripheral Stem Cell Support
    5. Peripheral Stem Cell Transplant
    6. Peripheral Stem Cell Transplantation
    type
    PROCEDURE
  9. arm Group Labels
    1. Arm A (MRD)
    2. Arm B (MRD)
    3. Arm C (MUD)
    4. Arm D (MUD)
    description
    Given IV or PO
    name
    Tacrolimus
    other Names
    1. FK 506
    2. Fujimycin
    3. Hecoria
    4. Prograf
    5. Protopic
    type
    DRUG
  10. arm Group Labels
    1. Arm A (MRD)
    2. Arm B (MRD)
    3. Arm C (MUD)
    4. Arm D (MUD)
    description
    Given IV
    name
    Thiotepa
    other Names
    1. 1,1',1''-Phosphinothioylidynetrisaziridine
    2. Girostan
    3. N,N', N''-Triethylenethiophosphoramide
    4. Oncotiotepa
    5. STEPA
    6. Tepadina
    7. TESPA
    8. Tespamin
    9. Tespamine
    10. Thio-Tepa
    11. Thiofosfamide
    12. Thiofozil
    type
    DRUG
  11. arm Group Labels
    1. Arm A (MRD)
    2. Arm B (MRD)
    3. Arm C (MUD)
    description
    Undergo TBI
    name
    Total-Body Irradiation
    other Names
    1. Total Body Irradiation
    2. Whole-Body Irradiation
    3. TBI
    4. Whole Body Irradiation
    type
    RADIATION
Study design
allocation
NON_RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
84
type
ACTUAL
Registered outcome plans (not posted results)
other Outcomes
  1. description
    Use of additional immune suppressive agents other than first line therapy (prednisone and tacrolimus/cyclosporine)
    measure
    Other Immunosuppressive Agents
    time Frame
    Up to 5 years
  2. description
    Requirement for secondary systemic therapy for acute graft-versus-host disease (GVHD) management
    measure
    aGVHD Management - Secondary
    time Frame
    Up to day 100
  3. description
    Time to absolute neutrophil count (ANC) of \> 500/uL on the first of three consecutive days
    measure
    Engraftment - ANC >500/uL
    time Frame
    Through day 100 post-transplant
  4. description
    Time to absolute neutrophil count (ANC) of \> 1,000/uL on the first of three consecutive test results
    measure
    Engraftment - ANC <1,000/uL
    time Frame
    through Day 100 post-transplant
  5. description
    Time to platelet count \> 20,000/uL for 3 days without transfusion
    measure
    Platelet Engraftment
    time Frame
    Through day 100 post-transplant
  6. description
    Time to platelet count \> 50,000/uL for 3 days without transfusion
    measure
    Platelet Engraftment - 50,000/uL
    time Frame
    Through day 100 post-transplant
  7. description
    Will be analyzed from peripheral blood or marrow.
    measure
    Chimerism Analysis
    time Frame
    Up to 360 days
primary Outcomes
  1. description
    Occurrence of chronic graft-versus-host disease (GHVD), defined operationally as the occurrence of compatible symptoms meeting National Institutes of Health criteria and requiring systemic pharmacological immunosuppression.
    measure
    Chronic GVHD
    time Frame
    Up to 5 years post-transplant
  2. description
    Measure the number of days to discontinuation of prednisone in recipients of CD45RA+ T cell-depleted PBSCT by arm. Possible outcomes range from no systemic immunosuppression (best outcome) to 5 years on immunosuppression (poor outcome)
    measure
    Time to Completion of Prednisone
    time Frame
    Up to 5 years post-transplant
  3. description
    Measure the number of days to discontinuation of all immunosuppression in recipients of CD45RA+ T cell-depleted PBSCT by arm. Possible outcomes range from no systemic immunosuppression (best outcome) to 5 years on immunosuppression (poor outcome)
    measure
    Time to Completion of All Immunosuppression
    time Frame
    Up to 5 years post-transplant
  4. description
    Number of patients requiring immunosuppression 2 years after transplant.
    measure
    Requirement of Immunosuppression at 2 Years After Transplant
    time Frame
    At 2 years post transplant
  5. description
    Presence of acute graft-versus-host disease (GVHD) grades II-IV, defined operationally as the occurrence of compatible symptoms or signs in the skin, gastrointestinal tract, or liver, in patients who received Naive t cell depleted PBSCT. Staging and grading are found on page 8 of the JCO supplement (Bleakley et al., 2022, original references Glucksberg et all, 1974, Przepiorka et all, 1995 ) with higher grade indicating worse outcomes.
    measure
    Acute GVHD
    time Frame
    Through day 100 post-transplant
  6. description
    Defined operationally as failure to reach an absolute neutrophil count (ANC) of \> 500/ul for 3 consecutive days by day 28 or irreversible decrease in ANC to \< 100 after an established donor graft.
    measure
    Graft Failure
    time Frame
    Up to 5 years post-transplant
secondary Outcomes
  1. description
    Defined as mortality in any patient for whom there has not been a diagnosis of relapse.
    measure
    Transplant Related Mortality by Day 100
    time Frame
    Through day 100 post-transplant
  2. description
    Defined by the presence of malignant cells in marrow, peripheral blood, or extramedullary sites by histopathology.
    measure
    Relapse
    time Frame
    Up to 5 years post-transplant
Full study description
brief Summary
This phase II trial is for patients with acute lymphocytic leukemia, acute myeloid leukemia, myelodysplastic syndrome or chronic myeloid leukemia who have been referred for a peripheral blood stem cell transplantation to treat their cancer. In these transplants, chemotherapy and total-body radiotherapy ('conditioning') are used to kill residual leukemia cells and the patient's normal blood cells, especially immune cells that could reject the donor cells. Following the chemo/radiotherapy, blood stem cells from the donor are infused. These stem cells will grow and eventually replace the patient's original blood system, including red cells that carry oxygen to our tissues, platelets that stop bleeding from damaged vessels, and multiple types of immune-system white blood cells that fight infections. Mature donor immune cells, especially a type of immune cell called T lymphocytes (or T cells) are transferred along with these blood-forming stem cells. T cells are a major part of the curative power of transplantation because they can attack leukemia cells that have survived the chemo/radiation therapy and also help to fight infections after transplantation. However, donor T cells can also attack a patient's healthy tissues in an often-dangerous condition known as Graft-Versus-Host-Disease (GVHD). Drugs that suppress immune cells are used to decrease the severity of GVHD; however, they are incompletely effective and prolonged immunosuppression used to prevent and treat GVHD significantly increases the risk of serious infections. Removing all donor T cells from the transplant graft can prevent GVHD, but doing so also profoundly delays infection-fighting immune reconstitution and eliminates the possibility that donor immune cells will kill residual leukemia cells. Work in animal models found that depleting a type of T cell, called naïve T cells or T cells that have never responded to an infection, can diminish GVHD while at least in part preserving some of the benefits of donor T cells including resistance to infection and the ability to kill leukemia cells. This clinical trial studies how well the selective removal of naïve T cells works in preventing GVHD after peripheral blood stem cell transplants. This study will include patients conditioned with high or medium intensity chemo/radiotherapy who can receive donor grafts from related or unrelated donors.
detailed Description
OUTLINE: Patients are assigned to 1 of 4 treatment arms. CONDITIONING: ARMS A AND C (high-intensity myeloablative conditioning): Patients undergo total body irradiation twice daily (BID) on days -10 to -7. Patients also receive thiotepa intravenously (IV) over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. ARMS B AND D (lower-intensity myeloablative conditioning): Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation once daily (QD) on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with granulocyte colony-stimulating factor (GCSF)-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: ARMS A AND C: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or orally (PO) (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. ARMS B AND D: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on days -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the principal investigator. After completion of study treatment, patients are followed up at 80-100 days, 360 days, and then yearly for up to 5 years.
Source references
references
  1. citation
    Bleakley M, Sehgal A, Seropian S, Biernacki MA, Krakow EF, Dahlberg A, Persinger H, Hilzinger B, Martin PJ, Carpenter PA, Flowers ME, Voutsinas J, Gooley TA, Loeb K, Wood BL, Heimfeld S, Riddell SR, Shlomchik WD. Naive T-Cell Depletion to Prevent Chronic Graft-Versus-Host Disease. J Clin Oncol. 2022 Apr 10;40(11):1174-1185. doi: 10.1200/JCO.21.01755. Epub 2022 Jan 10.
    pmid
    35007144
    type
    RESULT
Source notices and limitations
    Discovery and provenance
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      source json pointer
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      source kind
      ctgov_condition_query
      source record id
      Source null
      source string basis
      parsed_JSON_string_unmodified
      source string sha256
      c6a059af97f7d8d386b007521317744cd366bcd8602ded6cdaf32b0ed3a9fc28
    2. release id
      ctgov-registry-1336d216cbd1bbff780dac70
      edge id
      nct-edge-340d3d3b0ac07c4990fa
      requested nct id
      NCT02220985
      primary nct id
      NCT02220985
      source kind
      ctgov_condition_query
      source record id
      Source null
      source file sha256
      193739e64f77123de4344901c9970a0996a667fa587f14135380bef3ae38e11d
      payload sha256
      8aa447d923027bbb1addedf9c137261dae8e23c19165bac687c250b4706d8d10
      payload
      clinical indication matching status
      condition_index_match_asserted_by_registry_not_reviewed
      end exclusive
      true
      id
      nct-edge-340d3d3b0ac07c4990fa
      link basis
      returned_by_explicit_condition_and_posted_results_filter_query
      nct id
      NCT02220985
      occurrences
      1. context exact
        NCT02220985
        end
        11
        exact text
        NCT02220985
        start
        0
      offset unit
      unicode_code_points
      query cond
      Childhood Chronic Myeloid Leukemia
      query disease state id
      ds-chronic-myeloid-leukemia-pediatric
      source file
      /Users/arunverma/Documents/ChatGPT/Cancer Statistics Website/research-data/2026-09-10/clinicaltrials-condition/round-0000/raw/cond-childhood-chronic-myeloid-leukemia-000.json
      source file sha256
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      source json pointer
      /studies/27/protocolSection/identificationModule/nctId
      source kind
      ctgov_condition_query
      source record id
      Source null
      source string basis
      parsed_JSON_string_unmodified
      source string sha256
      c6a059af97f7d8d386b007521317744cd366bcd8602ded6cdaf32b0ed3a9fc28
    3. release id
      ctgov-registry-1336d216cbd1bbff780dac70
      edge id
      nct-edge-be422d5733c85c4ea055
      requested nct id
      NCT02220985
      primary nct id
      NCT02220985
      source kind
      ctgov_condition_query
      source record id
      Source null
      source file sha256
      1f6ffef8d557bd3ff6e7738a80f73b58dddfc3fab889f2661577c6dd238f078c
      payload sha256
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      payload
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      true
      id
      nct-edge-be422d5733c85c4ea055
      link basis
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      nct id
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      occurrences
      1. context exact
        NCT02220985
        end
        11
        exact text
        NCT02220985
        start
        0
      offset unit
      unicode_code_points
      query cond
      Infant Acute Undifferentiated Leukemia
      query disease state id
      ds-infant-acute-undifferentiated-leukemia
      source file
      /Users/arunverma/Documents/ChatGPT/Cancer Statistics Website/research-data/2026-09-10/clinicaltrials-condition/round-0000/raw/cond-infant-acute-undifferentiated-leukemia-000.json
      source file sha256
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      source json pointer
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      source kind
      ctgov_condition_query
      source record id
      Source null
      source string basis
      parsed_JSON_string_unmodified
      source string sha256
      c6a059af97f7d8d386b007521317744cd366bcd8602ded6cdaf32b0ed3a9fc28
    4. release id
      ctgov-registry-1336d216cbd1bbff780dac70
      edge id
      nct-edge-c3456991597745ddedfb
      requested nct id
      NCT02220985
      primary nct id
      NCT02220985
      source kind
      ctgov_condition_query
      source record id
      Source null
      source file sha256
      a4be8fb2a7db9247bdfed231ef84ae19b3babbe8d619ebf7403cceb730eae2d4
      payload sha256
      2f04193665dd7c1de6b6919f9b72e801f0618e8c403dda4e8028b983bfb26eb2
      payload
      clinical indication matching status
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      true
      id
      nct-edge-c3456991597745ddedfb
      link basis
      returned_by_explicit_condition_and_posted_results_filter_query
      nct id
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      occurrences
      1. context exact
        NCT02220985
        end
        11
        exact text
        NCT02220985
        start
        0
      offset unit
      unicode_code_points
      query cond
      Childhood Myelodysplastic Neoplasms
      query disease state id
      ds-myelodysplastic-neoplasms-pediatric
      source file
      /Users/arunverma/Documents/ChatGPT/Cancer Statistics Website/research-data/2026-09-10/clinicaltrials-condition/round-0000/raw/cond-childhood-myelodysplastic-neoplasms-000.json
      source file sha256
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      source json pointer
      /studies/31/protocolSection/identificationModule/nctId
      source kind
      ctgov_condition_query
      source record id
      Source null
      source string basis
      parsed_JSON_string_unmodified
      source string sha256
      c6a059af97f7d8d386b007521317744cd366bcd8602ded6cdaf32b0ed3a9fc28

    Preserved source evidence · Not medical advice