Breast CancerPhase 2NCT00376805
Allogeneic Natural Killer (NK) Cells in Patients With Advanced Metastatic Breast Cancer
A Phase 2 study testing Fludarabine, Cyclophosphamide and Total body irradiation in people with Breast Cancer, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Fludarabine, Cyclophosphamide and Total body irradiation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2006to Jan 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 18Show fewer
- 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)
Who cannot join
- At least 3 days since prior prednisone or other immunosuppressive medications
- No other concurrent therapy for cancer
Trial locations and contacts
1 site in 1 country.
United States1 site
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: Allogeneic Natural Killer Cells in Patients With Advanced Metastatic Breast Cancer
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.
Read the 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.
- Conditions
- Breast Cancer
- Being tested
- Fludarabine, Cyclophosphamide, Total body irradiation, Natural killer cell infusion, Interleukin-2
- Keywords
- stage IV breast cancer, male breast cancer, recurrent breast cancer
- Medical subject headings
- Breast Neoplasms, Breast Neoplasms, Male
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FludarabineDrug
Also called Fludara
administered intravenously 25 mg/m^2 times 5 doses
CyclophosphamideDrug
Also called Endoxan, Cytoxan, Neosar, Procytox
administered intravenously 60 mg/kg days times 2 doses.
Total body irradiationRadiation
Also called radiation
200 cGy (gray) on day -1
Natural killer cell infusionOther
Also called NK cells
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-2Biological
Also called IL-2
administered subcutaneously (10 MU) 3 times per week for 6 doses
| Study group | Role | What they receive |
|---|---|---|
| All Treated Patients | Experimental | All patients with advanced metastatic breast cancer treated with natural killer cells after receiving fludarabine, cyclosphosphamide and total body irradiation. Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total body irradiation; Other: Natural killer cell infusion; Biological: Interleukin-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Day 14
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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).
Measured: First Day of Treatment Until Death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2006 (estimated)
- Study startApr 2006
- Primary completionSep 2009
- Study completionJan 2010
Why it stopped: Withdrawn due to toxicity
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Masonic Cancer Center, University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jeffrey Miller, MD, Study chair, Masonic Cancer Center, University of MinnesotaSarah Cooley, MD, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00376805
- Sponsor's protocol ID
- UMN-2005LS033
- Other IDs
- UMN-0505M70037, UMN-MT2005-08
- Status last verified
- Dec 2017
- First submitted
- 13 Sep 2006
- Last updated
- 28 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Allogeneic Natural Killer Cells in Patients With Advanced Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00376805
- Acronym / sponsor ID
- UMN-2005LS033
- Conditions
- Breast Cancer
- Keywords
- stage IV breast cancer, male breast cancer, recurrent breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Withdrawn due to toxicity
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- Apr 2006
- Primary completion
- Sep 2009 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 15 Sep 2006 (estimated)
- Results
- Posted 12 Aug 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All Treated Patients | Experimental | Drug: Fludarabine, Drug: Cyclophosphamide, Radiation: Total body irradiation, Other: Natural killer cell infusion, Biological: Interleukin-2All patients with advanced metastatic breast cancer treated with natural killer cells after receiving fludarabine, cyclosphosphamide and total body irradiation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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)
Key exclusion criteria (2 listed)
- At least 3 days since prior prednisone or other immunosuppressive medications
- No other concurrent therapy for cancer
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FludarabineAlso: Fludaraadministered intravenously 25 mg/m^2 times 5 doses | Drug | All Treated Patients |
| CyclophosphamideAlso: Endoxan, Cytoxan, Neosar, Procytoxadministered intravenously 60 mg/kg days times 2 doses. | Drug | All Treated Patients |
| Total body irradiationAlso: radiation200 cGy (gray) on day -1 | Radiation | All Treated Patients |
| Natural killer cell infusionAlso: NK cellsInfused 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 | All Treated Patients |
| Interleukin-2Also: IL-2administered subcutaneously (10 MU) 3 times per week for 6 doses | Biological | All Treated Patients |
Primary outcome
Number of Patients Who Had Expansion of Natural Killer Cells
Time frame: Day 14
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).
3 secondary outcomes
Number of Patients by Disease Response
Time frame: 6 Months, 1 Year
Number of Patients Who Died While on Study
Time frame: Within 100 days, After 100 days
Overall Median Number of Days Patients Alive After Treatment
Time frame: First Day of Treatment Until Death
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey Miller, MD study chair
Masonic Cancer Center, University of Minnesota
Sarah Cooley, MD principal investigator
Masonic Cancer Center, University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fludarabine, Cyclophosphamide and Total body irradiation in people with Breast Cancer, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Aug 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients Who Had Expansion of Natural Killer Cells (time frame: Day 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Dec 2017.