Clinical trial NCT00376805: Allogeneic Natural Killer (NK) Cells in Patients With Advanced Metastatic Breast Cancer
Official title: Allogeneic Natural Killer Cells in Patients With Advanced Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: stage IV breast cancer
male breast cancer
recurrent breast cancer
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2006-09-15
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Number of Patients Who Had Expansion of Natural Killer Cells
timeFrame: Day 14
Secondary outcomes:
measure: Number of Patients by Disease Response
timeFrame: 6 Months, 1 Year
measure: Number of Patients Who Died While on Study
timeFrame: Within 100 days, After 100 days
measure: Overall Median Number of Days Patients Alive After Treatment
timeFrame: First Day of Treatment Until Death
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Jeffrey Miller, MD
role: STUDY_CHAIR
affiliation: Masonic Cancer Center, University of Minnesota
name: Sarah Cooley, MD
role: PRINCIPAL_INVESTIGATOR
References: