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| ID | Type | Description | Link |
|---|---|---|---|
| R01AI053193 | U.S. NIH Grant/Contract | View source | |
| P30CA015704 | U.S. NIH Grant/Contract | View source | |
| FHCRC-1965.00 | |||
| CDR0000533834 | Registry Identifier | PDQ |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
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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.
OBJECTIVES:
Primary
Secondary
OUTLINE: Patients are stratified according to age (≤ 7 years vs > 7 years).
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.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| muromonab-CD3 | Biological | |||
| natural killer cell therapy | Biological | |||
| fludarabine phosphate | Drug | |||
| methotrexate | Drug | |||
| thiotepa | Drug | |||
| gene expression analysis | Genetic | |||
| flow cytometry | Other | |||
| Measure | Description | Time Frame |
|---|---|---|
| Risk of Developing Grades III-IV Acute Graft-vs-host Disease (GVHD) | Count of participants with acute GVHD grades III-IV. | Up to day 100 |
| Measure | Description | Time Frame |
|---|---|---|
| Risk for Mortality From Infection Before Day 180 | Count of participant deaths from infection up to day 180. | Up to day 180 |
| Risk for Graft Failure | Count of participant that had graft failure. |
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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:
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:
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
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
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| Name | Affiliation | Role |
|---|---|---|
| Ann Woolfrey, MD | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Seattle Cancer Care Alliance | Seattle | Washington | 98109-1023 | United States | ||
| Fred Hutchinson Cancer Research Center |
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment | Following total-body irradiation, thiotepa, fludarabine, and muromonab-CD3, participants are given a donor peripheral stem cell transplant and a donor natural killer cell transplant. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| immunologic technique |
| Other |
| allogeneic hematopoietic stem cell transplantation | Procedure |
| in vitro-treated peripheral blood stem cell transplantation | Procedure |
| total-body irradiation | Radiation |
| Engraftment documented day +20 |
| Risk for Life-threatening Infections | Count of participants with life-threatening infections | Up to day 100 |
| Concentration of NK, NK-T, T-cells, and Dendritic Cell Subsets in the CD34+ NK/NK-T-enriched Graft | Up to 5 years |
| Cytomegalovirus-specific T Cells in Product and Donor Graft | Up to 5 years |
| Genotype and Phenotype of Donor Killer Cell Immunoglobulin-like Receptor Expression According to Time After Hematopoietic Stem Cell Transplantation (HSCT) | Up to 5 years |
| Reconstitution of NK Function According to Time After HSCT | Up to 5 years |
| Expression of NKG2 Ligands of Leukemic Blasts | Up to 5 years |
| Seattle |
| Washington |
| 98109-1024 |
| United States |
| COMPLETED |
|
| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment | Following total-body irradiation, thiotepa, fludarabine, and muromonab-CD3, participants are given a donor peripheral stem cell transplant and a donor natural killer cell transplant. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Risk of Developing Grades III-IV Acute Graft-vs-host Disease (GVHD) | Count of participants with acute GVHD grades III-IV. | Posted | Count of Participants | Participants | Up to day 100 |
|
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| Secondary | Risk for Mortality From Infection Before Day 180 | Count of participant deaths from infection up to day 180. | Posted | Count of Participants | Participants | Up to day 180 |
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| Secondary | Risk for Graft Failure | Count of participant that had graft failure. | Posted | Count of Participants | Participants | Engraftment documented day +20 |
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| ||||||||||||||||||||||||||||
| Secondary | Risk for Life-threatening Infections | Count of participants with life-threatening infections | Posted | Count of Participants | Participants | Up to day 100 |
|
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| Secondary | Concentration of NK, NK-T, T-cells, and Dendritic Cell Subsets in the CD34+ NK/NK-T-enriched Graft | Analysis for this endpoint not feasible due to funding constraint. | Posted | Up to 5 years |
|
| ||||||||||||||||||||||||||||||
| Secondary | Cytomegalovirus-specific T Cells in Product and Donor Graft | Analysis for this endpoint not feasible due to funding constraint. | Posted | Up to 5 years |
|
| ||||||||||||||||||||||||||||||
| Secondary | Genotype and Phenotype of Donor Killer Cell Immunoglobulin-like Receptor Expression According to Time After Hematopoietic Stem Cell Transplantation (HSCT) | Analysis for this endpoint not feasible due to funding constraint. | Posted | Up to 5 years |
|
| ||||||||||||||||||||||||||||||
| Secondary | Reconstitution of NK Function According to Time After HSCT | Analysis for this endpoint not feasible due to funding constraint. | Posted | Up to 5 years |
|
| ||||||||||||||||||||||||||||||
| Secondary | Expression of NKG2 Ligands of Leukemic Blasts | Analysis for this endpoint not feasible due to funding constraint. | Posted | Up to 5 years |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment | Following total-body irradiation, thiotepa, fludarabine, and muromonab-CD3, participants are given a donor peripheral stem cell transplant and a donor natural killer cell transplant. | 0 | 1 | 0 | 1 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ann Woolfrey, MD | Fred Hutchinson Cancer Research Center | 206-667-4453 | awoolfre@fredhutch.org |
| ID | Term |
|---|---|
| D006086 | Graft vs Host Disease |
| D007938 | Leukemia |
| D009190 | Myelodysplastic Syndromes |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D000013 | Congenital Abnormalities |
| D015470 | Leukemia, Myeloid, Acute |
| D015465 | Leukemia, Myeloid, Accelerated Phase |
| D001752 | Blast Crisis |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D001855 | Bone Marrow Diseases |
| D007945 | Leukemia, Lymphoid |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007951 | Leukemia, Myeloid |
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| D009196 | Myeloproliferative Disorders |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D002471 | Cell Transformation, Neoplastic |
| D063646 | Carcinogenesis |
| D009385 | Neoplastic Processes |
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| ID | Term |
|---|---|
| D016853 | Muromonab-CD3 |
| C042382 | fludarabine phosphate |
| D008727 | Methotrexate |
| D013852 | Thiotepa |
| D020869 | Gene Expression Profiling |
| D005434 | Flow Cytometry |
| D007158 | Immunologic Techniques |
| D014916 | Whole-Body Irradiation |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D007074 | Immunoglobulin G |
| D007132 | Immunoglobulin Isotypes |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D013721 | Triethylenephosphoramide |
| D001388 | Aziridines |
| D001389 | Azirines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D005821 | Genetic Techniques |
| D008919 | Investigative Techniques |
| D002469 | Cell Separation |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D003592 | Cytophotometry |
| D005470 | Fluorometry |
| D008163 | Luminescent Measurements |
| D010783 | Photometry |
| D002623 | Chemistry Techniques, Analytical |
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
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| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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