| ID | Type | Description | Link |
|---|---|---|---|
| UMN-0505M70037 | Other Identifier | IRB, University of Minnesota | |
| UMN-MT2005-08 | Other Identifier | Blood and Bone Marrow Transplantation Program |
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Withdrawn due to toxicity
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RATIONALE: Giving chemotherapy before a donor natural killer (NK) cell infusion helps stop the growth of tumor cells. It also helps stop the patient's immune system from rejecting the donor's cells. Giving NK cells from a related donor may kill the tumor cells.
PURPOSE: This study furthers the research of previous studies (MT2003-01 and MT2004-25) which were to determine a specific preparatory regimen (cyclophosphamide and fludarabine) could create an environment in which infused NK cells can grow and effectively treat patients with relapsed AML. This study will test the previous regimen in patients with breast cancer.
We believe that administration of related allogeneic (donor) natural killer cells along with IL-2, rather than autologous natural killer cells will provide the most effective anticancer therapy in this setting, and wish to test this approach. To do this, we will select a related donor who is partially HLA-matched with the study subject, to increase the likelihood that donor natural killer cells will kill the subject's cancer cells. We will also give chemotherapy drugs to increase the subject's tolerance for the donor natural killer cells. We will test the use of donor natural killer (NK) cell infusions. The immune system has a special way that it sees and identifies cancer cells or foreign agents (like viruses). The subject's own NK cells may not attack their cancer because NK cells see the tumor cells as "self" (a coating on the cell surface identifies a cell as "self" or "non-self"). We have reason to believe that NK cells may not kill cancer cells because NK cells have special receptors that "turn them off" when they encounter cancer cells (by seeing them as "self"). We may be able to get around this problem by using donor NK cells. Finally, subjects will receive a dose of subcutaneous IL-2 3 times a week (for 2 weeks) which has been proven safe in our previous studies to stimulate the natural killer cells.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| All Treated Patients | Experimental | All patients with advanced metastatic breast cancer treated with natural killer cells after receiving fludarabine, cyclosphosphamide and total body irradiation. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fludarabine | Drug | administered intravenously 25 mg/m^2 times 5 doses |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients Who Had Expansion of Natural Killer Cells | Successful Natural Killer (NK) cell expansion is defined as detection of an absolute circulating donor-derived NK cell count of >100 cells/ul of whole blood 14 days after infusion with <5% donor T and B cells in mononuclear population (in metastatic breast cancer patients). | Day 14 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients by Disease Response | Defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria:
of clinical benefit (CB; stable disease for greater than 6 months. |
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Inclusion criteria:
Diagnosis of metastatic breast cancer that has progressed on or failed at least one salvage chemotherapy regimen for metastatic disease and that meets the following disease specific related criteria:
Related HLA-haploidentical natural killer cell donor available (by ≥ class I serologic typing)
Male or female
Performance status 50-100%
Platelet count ≥ 80,000/mm³ (unsupported by transfusions)
Hemoglobin ≥ 9 g/dL (unsupported by transfusions)
Absolute neutrophil count ≥ 1,000/mm³ (unsupported by sargramostim [GM-CSF] or filgrastim [G-CSF])
Creatinine ≤ 2.0 mg/dL
Liver function tests < 5 times normal
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
LVEF > 40%*
Pulmonary function > 50%* (DLCO corrected AND FEV_1)
No active infection (i.e., afebrile, off antibiotics, and no uninvestigated radiologic lesions)
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jeffrey Miller, MD | Masonic Cancer Center, University of Minnesota | Study Chair |
| Sarah Cooley, MD | Masonic Cancer Center, University of Minnesota | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Masonic Cancer Center at University of Minnesota | Minneapolis | Minnesota | 55455 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | NK Cells With or Without Total Body Irradiation | Patients receiving natural killer cell infusion, fludarabine and cyclosphosphamide preparatory regimen, and with or without total body irradiation for treatment of metastatic breast cancer. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | NK Cells With or Without Total Body Irradiation | Patients receiving natural killer cell infusion, fludarabine and cyclosphosphamide preparatory regimen, and with or without total body irradiation for treatment of metastatic breast cancer. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of 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 | Number of Patients Who Had Expansion of Natural Killer Cells | Successful Natural Killer (NK) cell expansion is defined as detection of an absolute circulating donor-derived NK cell count of >100 cells/ul of whole blood 14 days after infusion with <5% donor T and B cells in mononuclear population (in metastatic breast cancer patients). | Posted | Jul 2010 | Number | Participants | Day 14 |
|
|
All adverse events were collected up to patients' death (within 1 year of treatment).
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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 | NK Cells With or Without Total Body Irradiation | Patients receiving natural killer cell infusion, fludarabine and cyclosphosphamide preparatory regimen, and with or without total body irradiation for treatment of metastatic breast cancer. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bone marrow cellularity | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment | Marrow aplasia |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sarah Cooley, MD | Masonic Cancer Center, University of Minnesota | 612-625-8474 | cool0023@umn.edu |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D018567 | Breast Neoplasms, Male |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| C024352 | fludarabine |
| C042382 | fludarabine phosphate |
| D003520 | Cyclophosphamide |
| D014916 | Whole-Body Irradiation |
| D011827 | Radiation |
| D007376 | Interleukin-2 |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
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| Cyclophosphamide | Drug | administered intravenously 60 mg/kg days times 2 doses. |
|
|
| Total body irradiation | Radiation | 200 cGy (gray) on day -1 |
|
|
| Natural killer cell infusion | Other | Infused cell dose is within the range of 1.5-8.0 x 10^7/kg. Cell counts are based on total cells infused after the activation culture and washing determined on the morning of infusion. |
|
|
| Interleukin-2 | Biological | administered subcutaneously (10 MU) 3 times per week for 6 doses |
|
|
| 6 Months, 1 Year |
| Number of Patients Who Died While on Study | Number of patients who died within 100 days and after 100 days of natural killer (NK) treatment with or without total body irradiation. | Within 100 days, After 100 days |
| Overall Median Number of Days Patients Alive After Treatment | Calculated median number of days of survival (patients alive days after treatment). | First Day of Treatment Until Death |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Participants |
|
|
| Secondary | Number of Patients by Disease Response | Defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria:
of clinical benefit (CB; stable disease for greater than 6 months. | Posted | Jul 2010 | Number | Participants | 6 Months, 1 Year |
|
|
|
| Secondary | Number of Patients Who Died While on Study | Number of patients who died within 100 days and after 100 days of natural killer (NK) treatment with or without total body irradiation. | Posted | Jul 2010 | Number | Participants | Within 100 days, After 100 days |
|
|
|
| Secondary | Overall Median Number of Days Patients Alive After Treatment | Calculated median number of days of survival (patients alive days after treatment). | Posted | Jul 2010 | Median | 95% Confidence Interval | Days | First Day of Treatment Until Death |
|
|
|
| 6 |
| 6 |
| 6 |
| 6 |
|
| Death - disease progression NOS | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Death due to progressive disease | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Passenger lymphocyte syndrome | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment | Hemolysis |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fever | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Chills | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypertension | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypotension | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Edema | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment | Includes pulmonary infiltrates |
|
| Injection Site Reaction | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment | Includes desquamation |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment | Includes arthralgia |
|
| Sweats | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Anxiety | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hematuria | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cardiac function LVEF | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemolytic anemia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
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| D017437 |
| Skin and Connective Tissue Diseases |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D008919 | Investigative Techniques |
| D055585 | Physical Phenomena |
| D007378 | Interleukins |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D008222 | Lymphokines |
| D011506 | Proteins |
| D001685 | Biological Factors |