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NCT00914940 · REGISTRY CONDITION SEARCH

Selective Depletion of CD45RA+T Cells From Allogeneic Peripheral Blood Stem Cell Grafts for the Prevention of 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
TERMINATED
Registry last update
2020-08-20

RATIONALE: Allogeneic hematopoietic stem cell transplant (HSCT) is a treatment that can cure acute leukemia and myelodysplasia. After giving the patient chemotherapy and total body irradiation to stop the growth of cancer and remove the patient's diseased bone marrow, healthy stem cells from a donor are infused into the patient to replace the patient's bone marrow and make red and white blood cells and platelets. Unfortunately HSCT is often complicated by 'graft versus host disease' (GVHD) in which the transplanted cells from a donor can make an immune response against the body's normal cells and cause tissue damage and severe symptoms. Removing a subset of the donor T cells, called 'naive T cells', before transplant may reduce the frequency and intensity of GVHD. PURPOSE: This phase II trial will determine whether the removal of the naive T cells from donor cells can decrease the rate and severity of graft-vs-host disease while preserving specific immunity against infections in patients with acute leukemia or advanced myelodysplastic syndromes.

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

Number of Participants With Acute Graft-vs-host Disease (GVHD): Grade I-IV, Including Those With no Reportable Acute GVHD

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outcome · POSTED

Number of Participants Who Did Not Engraft After Receiving a CD45RA+ T Cell Depleted PBSC Transplant

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outcome · POSTED

Transplant-related Mortality by Day 100

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outcome · POSTED

Number of Participants Who Have Relapsed Within 5 Years of CD45RA+ T Cell Depleted PBSC Transplant

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outcome · POSTED

Number of Participants With Chronic GVHD

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
DISEASE CHARACTERISTICS: * Diagnosis of 1 of the following: * Acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML) in first or subsequent remission * ALL or AML in relapse or primary refractory ALL or AML with a circulating blast count ≤ 10,000/mm\^3 * Refractory anemia with excess blasts (RAEB) (RAEB-1 or RAEB-2) if the patient has received induction chemotherapy within the past 60 days * Appropriate candidate for allogeneic hematopoietic stem cell transplantation (HSCT) * No CNS involvement refractory to intrathecal chemotherapy and/or standard cranial-spinal radiotherapy PATIENT CHARACTERISTICS: * Age 14-55 * Creatinine \< 1.5 mg/dL * Cardiac ejection fraction \> 45% * DLCO corrected \> 60% of predicted * Total bilirubin \< 2 times upper limit of normal (ULN) (unless attributed to Gilbert syndrome) * AST and ALT \< 2 times ULN * Not pregnant or nursing * Fertile patients must use effective contraception during and for 12 months after transplantation * HIV negative * No co-existing disease (other than leukemia or RAEB) that would limit life expectancy to \< 3 months * No uncontrolled infection that, in the opinion of the consulting infectious disease physician, would contraindicate myeloablative HSCT * No other medical condition that would contraindicate HSCT * No known hypersensitivity to tacrolimus PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior HSCT * No concurrent participation in other experimental studies for the prevention of graft-vs-host disease DONOR CHARACTERISTICS: * Genotypic or phenotypic HLA-identical related donor * Able to donate peripheral blood stem cells * Age \> 14 years * Applicable to male patients only: No female donors who have previously given birth to a male child or have had a pregnancy beyond the first trimester miscarriage or termination of pregnancy or nursing * No donors who have received blood transfusions * No CD45 Mutation with aberrant CD45RA isoform expression
healthy Volunteers
false
maximum Age
55 Years
minimum Age
14 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. description
    CONDITIONING: Patients undergo total-body irradiation twice daily on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine IV over 30 minutes on days -6 to -2. TRANSPLANTATION: Patients undergo infusion of CD34+ enriched allogeneic peripheral blood stem cells (PBSC) followed by CD45RA+ T-cell-depleted allogeneic PBSC on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Cohort A: Patients receive tacrolimus IV continuously or orally twice daily beginning on day -1 and continuing until day 50 followed by standard taper in the absence of grade II-IV acute GVHD. Cohort B: Patients receive tacrolimus IV continuously or orally twice daily beginning on day -1 and continuing until day 30 followed by rapid taper in the absence of grade II-IV acute GVHD.
    intervention Names
    1. Drug: Fludarabine Phosphate
    2. Drug: Tacrolimus
    3. Drug: Thiotepa
    4. Radiation: Total-Body Irradiation (TBI)
    5. Other: Magnetic Affinity Cell Sorting
    6. Procedure: Peripheral Blood Stem Cell Transplantation
    7. Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
    8. Biological: T Cell-Depleted Hematopoietic Stem Cell Transplantation
    label
    Arm 1
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Arm 1
    description
    Fludarabine will be administered in a dose of 25 mg/m2/day IV over approximately 30 minutes for 5 consecutive days (day -6 to -2). The total dose of fludarabine will be 125 mg/m2.
    name
    Fludarabine Phosphate
    other Names
    1. 2-F-ara-AMP
    2. Beneflur
    3. Fludara
    type
    DRUG
  2. arm Group Labels
    1. Arm 1
    description
    Tacrolimus will be administered beginning on day -1 at a dose of 0.03 mg/kg/day by continuous IV infusion. For the first cohort of 35 patients, if there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus should then be tapered at the rate of approximately 5% of the day 50 dose each week for liquid, and 20% of the day 50 dose per month for capsules. In the second cohort of 25 patients if there is no evidence of grade II GVHD on or prior to day 30, tacrolimus should then be tapered at the rate of approximately 8% of the day 30 dose each week for liquid, and 33% of the day 30 dose per month for capsules.
    name
    Tacrolimus
    other Names
    1. Advagraf
    2. FK 506
    3. Prograf
    4. Protopic
    type
    DRUG
  3. arm Group Labels
    1. Arm 1
    description
    Thiotepa will be administered in a dose of 5 mg/kg/day (adjusted body weight) IV over approximately 4 hours for 2 consecutive days (day -6 and day -5).
    name
    Thiotepa
    other Names
    1. Oncotiotepa
    2. STEPA
    3. TESPA
    4. Tespamin
    5. Tespamine
    6. TSPA
    type
    DRUG
  4. arm Group Labels
    1. Arm 1
    description
    TBI will be given as 165 cGy fractions twice per day x 4 days - total dose 1320cGy (days -10 to -7).
    name
    Total-Body Irradiation (TBI)
    other Names
    1. TBI
    type
    RADIATION
  5. arm Group Labels
    1. Arm 1
    description
    Device
    name
    Magnetic Affinity Cell Sorting
    other Names
    1. Magnetic-Activated Cell Sorter (CliniMACS, Miltenyi)
    type
    OTHER
  6. arm Group Labels
    1. Arm 1
    description
    Patient will undergo a PBSC transplantation
    name
    Peripheral Blood Stem Cell Transplantation
    other Names
    1. PBPC transplantation
    2. PBSC transplantation
    3. Peripheral Blood Progenitor Cell Transplantation
    4. Transplantation
    5. Peripheral Blood Stem Cell
    type
    PROCEDURE
  7. arm Group Labels
    1. Arm 1
    description
    Patients who are considered appropriate candidates for allogeneic hematopoietic stem cell transplantation
    name
    Allogeneic Hematopoietic Stem Cell Transplantation
    type
    PROCEDURE
  8. arm Group Labels
    1. Arm 1
    description
    Patients who are eligible will receive a T Cell-Depleted Hematopoietic Stem Cell Transplantation
    name
    T Cell-Depleted Hematopoietic Stem Cell Transplantation
    type
    BIOLOGICAL
Study design
allocation
NA
intervention Model
SINGLE_GROUP
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
41
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    Number of participants with aGVHD and severity of aGVHD within the first 360 days post-transplant as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Acute GVHD is graded by standard criteria, and all suspected cases of acute GVHD will be confirmed histologically by biopsy of an affected organ. The severity of acute GVHD is determined by an assessment of the degree of involvement of the skin, liver, and gastrointestinal tract. Grade I is characterized as mild disease, Grade II as moderate, Grade III as severe (involvement of any organ system), and Grade IV as life-threatening.
    measure
    Number of Participants With Acute Graft-vs-host Disease (GVHD): Grade I-IV, Including Those With no Reportable Acute GVHD
    time Frame
    Within 360 days of transplant
  2. description
    Graft failure is defined as either a failure to reach an ANC of \>500/uL for 3 consecutive days by day 28 post-transplant, or an irreversible decrease in ANC \<100 after an established donor graft, unless there is a reasonable explanation such as a viral infection or drug effect that may be responsible for a reversible decrease in ANC.
    measure
    Number of Participants Who Did Not Engraft After Receiving a CD45RA+ T Cell Depleted PBSC Transplant
    time Frame
    Up to 5 years post transplant
secondary Outcomes
  1. description
    Number of participants who died due to transplant-related issues within the first 100 days of transplant
    measure
    Transplant-related Mortality by Day 100
    time Frame
    Transplant to day 100
  2. description
    Relapse is defined by the presence of malignant cells in marrow, peripheral blood, or extramedullary sites by histopathology. Testing for recurrent malignancy in the blood and bone marrow performed by monitoring the CBC and bone marrow at Day 28, 58, 80, 360, and as needed for suspected relapse.
    measure
    Number of Participants Who Have Relapsed Within 5 Years of CD45RA+ T Cell Depleted PBSC Transplant
    time Frame
    Up to 5 years post transplant
  3. description
    Chronic GVHD measured by meeting NIH criteria and treated with immune suppression
    measure
    Number of Participants With Chronic GVHD
    time Frame
    Up to 5 years post transplant
Full study description
brief Summary
RATIONALE: Allogeneic hematopoietic stem cell transplant (HSCT) is a treatment that can cure acute leukemia and myelodysplasia. After giving the patient chemotherapy and total body irradiation to stop the growth of cancer and remove the patient's diseased bone marrow, healthy stem cells from a donor are infused into the patient to replace the patient's bone marrow and make red and white blood cells and platelets. Unfortunately HSCT is often complicated by 'graft versus host disease' (GVHD) in which the transplanted cells from a donor can make an immune response against the body's normal cells and cause tissue damage and severe symptoms. Removing a subset of the donor T cells, called 'naive T cells', before transplant may reduce the frequency and intensity of GVHD. PURPOSE: This phase II trial will determine whether the removal of the naive T cells from donor cells can decrease the rate and severity of graft-vs-host disease while preserving specific immunity against infections in patients with acute leukemia or advanced myelodysplastic syndromes.
detailed Description
OBJECTIVES: Primary * Estimate the probability of grades II-IV acute graft-vs-host disease (GVHD) in patients with acute leukemia or advanced myelodysplastic syndromes treated with CD45RA+ T-cell-depleted allogeneic peripheral blood stem cell transplantation and compare this to relevant historical experience. * Estimate the probability of graft failure in these patients. Secondary * Evaluate immune reconstitution and pathogen-specific T-cell reconstitution in these patients. * Estimate the probability of transplant-related mortality by day 100 in these patients. * Estimate the probability of relapse in these patients. * Estimate the probability and severity of chronic GVHD in these patients. OUTLINE: This is a multicenter study. * Myeloablative conditioning regimen: Patients undergo total body irradiation twice daily for 4 days (Days -10 to -7) Patients also receive thiotepa IV over 4 hours for 2 days (Days -6 and -5) and fludarabine phosphate IV over 30 minutes for 5 days (Days -6 to -2.) * Transplantation: Patients receive a CD34+ enriched allogeneic peripheral blood stem cell (PBSC) product followed by a CD45RA+ T-cell-depleted allogeneic PBSC product on day 0. * Graft-vs-host disease (GVHD) prophylaxis: Patients will receive Tacrolimus as per cohort 1. If the rate of grade II-IV acute GVHD in the first 35 patients is significantly reduced (compared to historical controls), subsequent patients are enrolled in cohort 2. * Cohort 1: Patients receive tacrolimus IV continuously or orally twice daily beginning on day -1 and continuing until day 50, followed by a standard taper in the absence of grade II-IV acute GVHD. * Cohort 2: Patients receive tacrolimus IV continuously or orally twice daily beginning on day -1 and continuing until day 30, followed by a rapid taper in the absence of grade II-IV acute GVHD. Patients are followed actively for at least 1 year post transplant.
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
    DERIVED
  2. citation
    Bleakley M, Heimfeld S, Loeb KR, Jones LA, Chaney C, Seropian S, Gooley TA, Sommermeyer F, Riddell SR, Shlomchik WD. Outcomes of acute leukemia patients transplanted with naive T cell-depleted stem cell grafts. J Clin Invest. 2015 Jul 1;125(7):2677-89. doi: 10.1172/JCI81229. Epub 2015 Jun 8.
    pmid
    26053664
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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    Preserved source evidence · Not medical advice