NCT00450983 · REGISTRY CONDITION SEARCH

Donor Peripheral Stem Cell Transplant and Donor Natural Killer Cell Transplant After Total-Body Irradiation, Thiotepa, Fludarabine, and Muromonab-CD3 in Treating Patients With Leukemia or Other Blood Diseases

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: 2017-05-24

RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell and donor natural killer cell transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When certain stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Removing the T cells from the donor cells before transplant may stop this from happening. PURPOSE: This phase II trial is studying how well giving a donor peripheral stem cell transplant and a donor natural killer cell transplant after total-body irradiation, thiotepa, fludarabine, and muromonab-CD3 works in treating patients with leukemia or other blood diseases.

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

Risk of Developing Grades III-IV Acute Graft-vs-host Disease (GVHD)

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outcome · POSTED

Risk for Mortality From Infection Before Day 180

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outcome · POSTED

Risk for Graft Failure

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outcome · POSTED

Risk for Life-threatening Infections

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outcome · POSTED

Concentration of NK, NK-T, T-cells, and Dendritic Cell Subsets in the CD34+ NK/NK-T-enriched Graft

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outcome · POSTED

Cytomegalovirus-specific T Cells in Product and Donor Graft

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outcome · POSTED

Genotype and Phenotype of Donor Killer Cell Immunoglobulin-like Receptor Expression According to Time After Hematopoietic Stem Cell Transplantation (HSCT)

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outcome · POSTED

Reconstitution of NK Function According to Time After HSCT

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outcome · POSTED

Expression of NKG2 Ligands of Leukemic Blasts

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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 life-threatening hematological malignancies: * Acute lymphoblastic leukemia meeting 1 of the following criteria: * Advanced beyond first remission * In first remission with high-risk prognostic features, including any of the following: * Philadelphia chromosome-positive disease * Chromosome 11q23 abnormality * Hypodiploid * Failed to achieve first remission within 1 month after induction * Acute myeloid leukemia (AML) meeting 1 of the following criteria: * Advanced beyond first remission * First remission with high-risk prognostic features, including any of the following: * Chromosome 11q23 abnormality * Chromosome del 7q * Secondary AML * Failed to achieve first remission within 1 month after induction * Myelodysplastic syndromes with International Prognostic Score \> 1 * Chronic myelogenous leukemia in accelerated or blastic phase * No active CNS disease * No suitable HLA-matched related or unrelated donor available * Haploidentical family member available as donor of partially HLA-matched peripheral blood stem cells * Least degree of mismatch to HLA-A, B, C, DRB1, and DQB1 * No mismatch for a single HLA-A, B, C, DRB1, or DQB1 antigen * Donor killer cell immunoglobulin-like receptor ligand group expression preferably different than patient PATIENT CHARACTERISTICS: * LVEF ≥ 45% * DLCO ≥ 60% of predicted * AST and ALT ≤ 2 times upper limit of normal (ULN) (unless due to malignancy) * Bilirubin ≤ 2 times ULN (unless due to malignancy) * No life expectancy \< 6 months due to coexisting disease other than the malignancy * No active infection (e.g., polymerase chain reaction \[PCR\] evidence for cytomegalovirus, human herpes virus 6, or invasive fungal infection) * No prior infections without evidence of resolution by PCR or imaging studies within the past 2 months * No hypersensitivity to murine antibodies * No known HIV positivity * Not pregnant or nursing * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: * No prior marrow transplantation with total body irradiation \> 400 cGy * No concurrent therapies for seizure disorder * No growth factors for 21 days after transplantation
healthy Volunteers: false
maximum Age: 45 Years
sex: ALL
std Ages: CHILD
ADULT

Treatment arms and interventions

interventions

name
muromonab-CD3
type
BIOLOGICAL
name
natural killer cell therapy
type
BIOLOGICAL
name
fludarabine phosphate
type
DRUG
name
methotrexate
type
DRUG
name
thiotepa
type
DRUG
name
gene expression analysis
type
GENETIC
name
flow cytometry
type
OTHER
name
immunologic technique
type
OTHER
name
allogeneic hematopoietic stem cell transplantation
type
PROCEDURE
name
in vitro-treated peripheral blood stem cell transplantation
type
PROCEDURE
name
total-body irradiation
type
RADIATION

Study design

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 1
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Count of participants with acute GVHD grades III-IV.
measure
Risk of Developing Grades III-IV Acute Graft-vs-host Disease (GVHD)
time Frame
Up to day 100

secondary Outcomes

description
Count of participant deaths from infection up to day 180.
measure
Risk for Mortality From Infection Before Day 180
time Frame
Up to day 180
description
Count of participant that had graft failure.
measure
Risk for Graft Failure
time Frame
Engraftment documented day +20
description
Count of participants with life-threatening infections
measure
Risk for Life-threatening Infections
time Frame
Up to day 100
measure
Concentration of NK, NK-T, T-cells, and Dendritic Cell Subsets in the CD34+ NK/NK-T-enriched Graft
time Frame
Up to 5 years
measure
Cytomegalovirus-specific T Cells in Product and Donor Graft
time Frame
Up to 5 years
measure
Genotype and Phenotype of Donor Killer Cell Immunoglobulin-like Receptor Expression According to Time After Hematopoietic Stem Cell Transplantation (HSCT)
time Frame
Up to 5 years
measure
Reconstitution of NK Function According to Time After HSCT
time Frame
Up to 5 years
measure
Expression of NKG2 Ligands of Leukemic Blasts
time Frame
Up to 5 years

Full study description

brief Summary: RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell and donor natural killer cell transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When certain stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Removing the T cells from the donor cells before transplant may stop this from happening. PURPOSE: This phase II trial is studying how well giving a donor peripheral stem cell transplant and a donor natural killer cell transplant after total-body irradiation, thiotepa, fludarabine, and muromonab-CD3 works in treating patients with leukemia or other blood diseases.
detailed Description: OBJECTIVES: Primary * Determine the effect of haploidentical donor CD34+ purified peripheral blood stem cells and donor natural killer (NK) cells on the risk of developing grades III-IV acute graft-vs-host disease in patients with leukemia or other hematologic diseases. Secondary * Determine the risk for mortality from infection before day 180 in patients treated with this regimen. * Determine the risk for graft rejection in patients treated with this regimen. * Determine the risk for life-threatening infections in patients treated with this regimen. * Determine the concentration of subsets of NK, NK-T, T cells, and dendritic cells in the CD34+ NK/NK-T-enriched graft. * Determine cytomegalovirus-specific T-cells in product and donor graft. * Determine the genotype and phenotype of donor killer cell immunoglobulin-like receptor expression according to time after hematopoietic stem cell transplantation (HSCT). * Determine the reconstitution of NK function according to time after HSCT. * Determine the expression of NKG2 ligands of leukemic blasts. OUTLINE: Patients are stratified according to age (≤ 7 years vs \> 7 years). * Conditioning regimen: Patients 7 years of age or younger undergo total-body irradiation (TBI) twice daily on days -11 to -9. Patients over 7 years of age undergo TBI once on day -9. All patients receive thiotepa IV over 2 hours on days -8 and -7, fludarabine phosphate IV on days -6 to -3 and muromonab-CD3 on days -6 to 6. Patients with acute lymphoblastic leukemia or leukemia in the spinal fluid also receive methotrexate intrathecally prior to and after donor peripheral blood stem cell (PBSC) transplantation . * Donor PBSC transplantation: Patients undergo donor PBSC transplantation comprising CD34+ purified PBSCs and natural killer (NK) cells on day 0. Blood samples are collected in weeks 1-4, 6, 8, and 12. Analysis of samples includes quantitation of NK, NK-T, and T-cell subsets (CD3, CD4, and CD8) by flow cytometry; donor killer cell immunoglobulin-like receptor genotype and phenotype; interferon-gamma levels; and NK cytotoxicity. Samples are also analyzed by leukemic blast assay to determine if ligands that activate NK cells are expressed. After completion of study therapy, patients are followed periodically. PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Source references

Source notices and limitations

Discovery and provenance

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Preserved source evidence · Not medical advice