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

Primary Purpose

Breast Cancer

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Fludarabine

Cyclophosphamide

Total body irradiation

Natural killer cell infusion

Interleukin-2

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring stage IV breast cancer, male breast cancer, recurrent breast cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Masonic Cancer Center at University of Minnesota

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

All Treated Patients

Arm Description

All patients with advanced metastatic breast cancer treated with natural killer cells after receiving fludarabine, cyclosphosphamide and total body irradiation.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Number of Patients by Disease Response

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

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

Calculated median number of days of survival (patients alive days after treatment).

Full Information

NCT ID

NCT00376805

First Posted

September 13, 2006

Last Updated

December 3, 2017

Sponsor

Masonic Cancer Center, University of Minnesota

1. Study Identification

Unique Protocol Identification Number

NCT00376805

Brief Title

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

2. Study Status

Record Verification Date

December 2017

Overall Recruitment Status

Terminated

Why Stopped

Withdrawn due to toxicity

Study Start Date

April 2006 (undefined)

Primary Completion Date

September 2009 (Actual)

Study Completion Date

January 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Masonic Cancer Center, University of Minnesota

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

Keywords

stage IV breast cancer, male breast cancer, recurrent breast cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

All Treated Patients

Arm Type

Experimental

Arm Description

All patients with advanced metastatic breast cancer treated with natural killer cells after receiving fludarabine, cyclosphosphamide and total body irradiation.

Intervention Type

Drug

Intervention Name(s)

Fludarabine

Other Intervention Name(s)

Fludara

Intervention Description

administered intravenously 25 mg/m^2 times 5 doses

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

Endoxan, Cytoxan, Neosar, Procytox

Intervention Description

administered intravenously 60 mg/kg days times 2 doses.

Intervention Type

Radiation

Intervention Name(s)

Total body irradiation

Other Intervention Name(s)

radiation

Intervention Description

200 cGy (gray) on day -1

Intervention Type

Other

Intervention Name(s)

Natural killer cell infusion

Other Intervention Name(s)

NK cells

Intervention Description

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.

Intervention Type

Biological

Intervention Name(s)

Interleukin-2

Other Intervention Name(s)

IL-2

Intervention Description

administered subcutaneously (10 MU) 3 times per week for 6 doses

Primary Outcome Measure Information:

Title

Number of Patients Who Had Expansion of Natural Killer Cells

Description

Time Frame

Day 14

Secondary Outcome Measure Information:

Title

Number of Patients by Disease Response

Description

Time Frame

6 Months, 1 Year

Title

Number of Patients Who Died While on Study

Description

Number of patients who died within 100 days and after 100 days of natural killer (NK) treatment with or without total body irradiation.

Time Frame

Within 100 days, After 100 days

Title

Overall Median Number of Days Patients Alive After Treatment

Description

Calculated median number of days of survival (patients alive days after treatment).

Time Frame

First Day of Treatment Until Death

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jeffrey Miller, MD

Organizational Affiliation

Masonic Cancer Center, University of Minnesota

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Sarah Cooley, MD

Organizational Affiliation

Masonic Cancer Center, University of Minnesota

Official's Role

Principal Investigator

Facility Information:

Facility Name

Masonic Cancer Center at University of Minnesota

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55455

Country

United States

12. IPD Sharing Statement

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

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