A Study Using White Blood Cells From Healthy Donors To Treat Solid Cancers

NCT00900497 | Enrolling By Invitation Phase 1

• 1 other identifier: 08001-BMSCTI
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

Background \& Rationale: About 75% of US population living today will not die of 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. The 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. Thus, a typical treatment in the study would span 1-2 weeks. 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.

Conditions

Solid Tumors

Keywords

granulocytes; Graft-vs-Host-Disease

Outcome Measures

Primary Outcomes (1)

• 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.

  90 to 100 days post treatment

Secondary Outcomes (1)

• 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

  1 to 2 weeks treatment and 30 days post treatment

Study Arms (1)

White Blood Cells/Granulocytes

EXPERIMENTAL

Fresh, non-irradiated granulocytes from ABO-Rh compatible, HLA-mismatched donors

Biological: White Blood Cells/Granulocytes

Interventions

White Blood Cells/Granulocytes BIOLOGICAL

Granulocytes collected by apheresis, cross-matched for ABO-Rh and common antibodies, HLA-mismatched to avoid engraftment

White Blood Cells/Granulocytes

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Uncontrolled diabetes mellitus, significant cardiac disease, e.g. recent myocardial infarction ≥ within 30 days, or active serious infection.
• HIV infection and no recent use (within 30 days) of immunosuppressive agents other than steroids.
• Pregnant or nursing women.
• Men or Women of reproductive age who are not using an effective means of birth control.
• Women of childbearing potential who have a positive serum pregnancy test prior to treatment.
• HLA Class I \& II antibodies.
• Neutrophil antibody test.
• Prior history of stem cell transplantation.
• Evidence of brain tumors or metastases.
• Prior history of fludarabine therapy.
• 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

Sponsors & Collaborators

• Dipnarine Maharaj: lead

Study Sites (1)

South Florida Bone Marrow / Stem Cell Transplant Institute

Boynton Beach, Florida, 33437, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Leukocyte Count

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Blood Cell Count; Cell Count; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Hematologic Tests; Investigative Techniques; Cell Physiological Phenomena; Blood Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Study Officials

• Dipnarine Maharaj, MD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Director

Study Record Dates

• First Submitted: May 11, 2009
• First Posted: May 12, 2009
• Study Start: April 1, 2009
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2030
• Last Updated: May 1, 2026

Record last verified: 2026-04

Locations

US (1)