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Allogeneic Natural Killer (NK) Cells in Patients With Advanced Metastatic Breast Cancer

This study has been terminated.
(Withdrawn due to toxicity)
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00376805
First received: September 13, 2006
Last updated: November 6, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: Fludarabine
Drug: Cyclophosphamide
Radiation: Total body irradiation
Other: Natural killer cell infusion
Biological: Interleukin-2
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Natural Killer Cells in Patients With Advanced Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Number of Patients Who Had Expansion of Natural Killer Cells [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Number of Patients by Disease Response [ Time Frame: 6 Months, 1 Year ] [ Designated as safety issue: No ]

    Defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria:

    • Complete Response (CR: Disappearance of all target lesions
    • Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions
    • Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or sufficient increase to qualify for PD
    • Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions of appearance of one or more new lesions

    of clinical benefit (CB; stable disease for greater than 6 months.


  • Number of Patients Who Died While on Study [ Time Frame: Within 100 days, After 100 days ] [ Designated as safety issue: Yes ]
    Number of patients who died within 100 days and after 100 days of natural killer (NK) treatment with or without total body irradiation.

  • Overall Median Number of Days Patients Alive After Treatment [ Time Frame: First Day of Treatment Until Death ] [ Designated as safety issue: No ]
    Calculated median number of days of survival (patients alive days after treatment).


Enrollment: 6
Study Start Date: April 2006
Study Completion Date: January 2010
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All Treated Patients
All patients with advanced metastatic breast cancer treated with natural killer cells after receiving fludarabine, cyclosphosphamide and total body irradiation.
Drug: Fludarabine
administered intravenously 25 mg/m^2 times 5 doses
Other Name: Fludara
Drug: Cyclophosphamide
administered intravenously 60 mg/kg days times 2 doses.
Other Name: Endoxan, Cytoxan, Neosar, Procytox
Radiation: Total body irradiation
200 cGy (gray) on day -1
Other Name: radiation
Other: Natural killer cell infusion
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.
Other Name: NK cells
Biological: Interleukin-2
administered subcutaneously (10 MU) 3 times per week for 6 doses
Other Name: IL-2

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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:

    • Measureable metastatic disease per Response Evaluation Criteria In Solid Tumor (RECIST) - bone only not eligible.
    • Disease progression while receiving prior therapy with a hormonal agent (if estrogen/progesterone receptor-positive) and/or trastuzumab (Herceptin®) (if HER2-neu positive)
    • Brain metastases allowed provided they are stable for ≥ 3 months after prior treatment
  • 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:

  • At least 3 days since prior prednisone or other immunosuppressive medications
  • No other concurrent therapy for cancer
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00376805

Locations
United States, Minnesota
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Study Chair: Jeffrey Miller, MD Masonic Cancer Center, University of Minnesota
Principal Investigator: Sarah Cooley, MD Masonic Cancer Center, University of Minnesota
  More Information

No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00376805     History of Changes
Obsolete Identifiers: NCT00167193
Other Study ID Numbers: UMN-2005LS033, UMN-0505M70037, UMN-MT2005-08
Study First Received: September 13, 2006
Results First Received: July 13, 2010
Last Updated: November 6, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
stage IV breast cancer
male breast cancer
recurrent breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Interleukin-2
Alkylating Agents
Analgesics
Analgesics, Non-Narcotic
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Central Nervous System Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014