A Study Using White Blood Cells From Healthy Donors To Treat Solid Cancers - Full Text View

Sponsor:	South Florida Bone Marrow/Stem Cell Transplant Institute
Information provided by:	South Florida Bone Marrow/Stem Cell Transplant Institute
ClinicalTrials.gov Identifier:	NCT00900497

Purpose

Background & Rationale:

About 75% of US population living today will not die of cancer. It is not uncommon that some people remain cancer-free into their 80s and 90s, even if they are regularly exposed to environmental carcinogens such as air pollutants, cigarette smoking, etc. A frequently asked but unanswered question is why these individuals do not get cancer. There has been a recent report of a colony of cancer-resistant mice developed from a single male mouse that unexpectedly survived challenges of lethal cancer cell injections. In these so-called spontaneous regression/complete resistant (SR/CR) mice, cancer cells are killed by rapid infiltration of leukocytes, mainly of innate immunity. This highly effective natural cancer immunity is inherited and mediated entirely by white blood cells. Moreover, this cancer resistance can be transferred to wild type mice through the transfer of various immune cell types including granulocytes.

This observation raises the possibility that infusion of white blood cells, particularly cells of innate immunity, is a viable anticancer therapy in humans as well.

This proposed trial will test whether white blood cell infusions from healthy unrelated donors can be used to treat cancer. The trial is designed to determine whether responses can be seen in cancer patients after infusion of HLA-mismatched white cells from healthy donors. It is important that the donors and recipients be unrelated and HLA-mismatched to avoid the possibility of transfusion-related Graft vs. Host Disease.

The white blood cells from the healthy donors are being collected via apheresis following granulocyte mobilization with dexamethasone and filgrastim. The investigators will refer to the white blood cells as 'granulocytes' because 75-90% of the white blood cells collected through the apheresis will consist of granulocytes.

The dose of at least 2x10 to the11th will be given from 4-5 donors at a rate of no more than one donor per day for each recipient. There will only be one infusion per day and no more than 5 infusions per week, but in many scenarios there may only be 3 days per week. Thus, a typical treatment in the study would span 1-2 weeks with up to a 4-day interval between 3rd and 4th infusion. After each infusion, the patients will be monitored carefully for possible adverse events. If adverse events occur at any time point during or after individual infusion, the treatment can be stopped until the adverse events can be managed. The daily dose of each infusion is a frequently used level that has a long safety record.

The trial will observe the subject's cancer for 3 months after the granulocyte infusions are completed. Response at 90 days will be based on comparison of tumor measurements at baseline.

The trial has 3 major endpoints: dose response and tolerance, safety, and efficacy.

Condition	Intervention	Phase
Solid (Non-hematological) Malignant Tumors	Biological: White Blood Cells	Phase I Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I/II Study For the Use of White Blood Cells From Healthy Donor-participants To Treat Subjects With Solid Cancers

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by South Florida Bone Marrow/Stem Cell Transplant Institute:

Primary Outcome Measures:

The trial will observe the subject's cancer status for 3 months after the granulocyte infusions are completed. Response at 90 days will be based on comparison of tumor measurements at baseline. [ Time Frame: 90 to 100 days post treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The trial will evaluate the safety and dose tolerance of the transfusion of non-irradiated granulocytes (approximately 4 to 6 donors to reach a level of 2 x 10 to the 11th cells) from HLA-mismatched donors [ Time Frame: 1 to 2 weeks treatment and 30 days post treatment ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	29
Study Start Date:	April 2009
Estimated Study Completion Date:	June 2012
Estimated Primary Completion Date:	April 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Granulocytes Fresh, non-irradiated granulocytes from ABO-Rh compatible, HLA-mismatched donors	Biological: White Blood Cells Granulocytes collected by apheresis, cross-matched for ABO-Rh and common antibodies, HLA-mismatched to avoid engraftment

Detailed Description:

Up to 29 Subjects with metastatic, non-hematological cancer can be entered. Potentially hundreds of healthy Donor-participants will be recruited. A Donor Registry will be built to store ABO/Rh-specific donors; these donors will be tested for HLA-specific genotyping as well as fully tested for infectious diseases.

Each patient will be receiving granulocytes from approximately 4 to 6 donors. Each donor will be HLA-mismatched to avoid engraftment of the granulocytes and any transfusion-related GVHD. These infusions will take place over a 1 to 2 week period, the timing of which will be dependent on both the subject's tolerance and the availability of the donors.

Subject Response Assessment:

For all patients not demonstrating disease progression, response status will be evaluated between Days +90 to +100 after the last infusion. Day+1 is the first day of white cell infusion. All measurable lesions (lesions that can be accurately measured in at least one dimension [longest diameter to be recorded] as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan) up to a maximum of 10 lesions representative of all involved organs should be identified as target lesions and will be recorded and measured at baseline. Target lesions should be selected on the basis of their size (lesions with the longest diameter) and their suitability for accurate repetitive measurements (either by imaging techniques or clinically). A sum of the longest diameter (LD) for all target lesions will be calculated and reported as the baseline sum LD. The baseline sum LD will be used as reference to further characterize the objective tumor response of the measurable dimension of the disease. The criteria for response, progression, and relapse are as follows.

Complete Response: Disappearance of all target lesions.
Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.
Progression (PD): At least a 20% increase in the sum of the LD of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD since the treatment started. Patients having a documented response with no reconfirmation of the response will be listed with stable disease.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria for Subjects:

Must have signed Subject Informed Consent form
Documentation of Disease: All patients must have histologically or cytologically confirmed non-hematological malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
Measurable Disease: Lesions that can be accurately measured in at least one dimension (longest diameter recorded) as ³20 mm with conventional technique or as ³10 mm with spiral CT scan.
Life expectancy of at least 4 months as judged by the PI at the time of consent
Performance status of ≤2 on the ECOG scale (see Appendix I).
≥ 4 weeks since prior medical therapy, radiation therapy, and surgery
Adequate organ function, such as absolute neutrophils ≥1,500/µl, platelet transfusion independent,
platelet count ≥100,000/µl, serum bilirubin ≤2 mg/dl, AST/ALT less than 3x upper limit of normal and serum creatinine ≤2 mg/dl.
No uncontrolled diabetes mellitus, significant cardiac disease, e.g. recent myocardial infarction ≥ within 30 days, or active serious infection.
No HIV infection and no recent use (within 30 days) of immunosuppressive agents other than steroids.
Women should not be pregnant or nursing while participating in this trial. Both men and women of reproductive potential should agree to use an effective means of birth control. Women of childbearing potential should have a negative serum pregnancy test before treatment.
Negative for HLA Class I & II antibodies.
Negative neutrophil antibody test.
No prior history of stem cell transplantation.
No evidence of brain tumors or metastases.
No prior history of fludarabine therapy.

Inclusion Criteria for Granulocyte Donors:

Must have signed Donor-participant Informed Consent Form
Must be a healthy, eligible blood donor who has completed Full-Length Universal Donor History Questionnaire version 1.2
Must be able to donate granulocytes and be willing to undergo granulocyte apheresis
Must have an HLA profile (A, B, DR) with results that ensure donated granulocytes will be mismatched with the recipient
Must have CMV negative or positive sero-testing completed; only seronegative donors are accepted for a seronegative recipient
Must have compatible ABO and RH typing with the subject
Must be negative for HLA Class I & II antibodies
Must have a negative Neutrophil antibody test
Must have a negative infectious disease workup within 30 days of apheresis / donation.
Must not have any known cardiac illness that could cause a potential risk associated with leukapheresis.
Must not have a genetic relationship to the recipient

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00900497

Locations

United States, Florida
South Florida Bone Marrow / Stem Cell Transplant Institute
Boynton Beach, Florida, United States, 33437

Sponsors and Collaborators

South Florida Bone Marrow/Stem Cell Transplant Institute

Investigators

Principal Investigator:

Dipnarine Maharaj, MD

Medical Director, South Florida Bone Marrow / Stem Cell Transplant Institute

More Information

No publications provided

Responsible Party:	Dipnarine Maharaj, MD; Principal Investigator, Medical Director, South Florida Bone Marrow / Stem Cell Transplant Institute
ClinicalTrials.gov Identifier:	NCT00900497 History of Changes
Other Study ID Numbers:	08001-BMSCTI
Study First Received:	May 11, 2009
Last Updated:	June 3, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by South Florida Bone Marrow/Stem Cell Transplant Institute:

granulocytes
Graft-vs-Host-Disease

Additional relevant MeSH terms:

Neoplasms

ClinicalTrials.gov processed this record on February 09, 2012