29 Participants Needed

White Blood Cell Infusions for Solid Cancers

Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: Dipnarine Maharaj
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must have completed any prior medical therapy, radiation therapy, or surgery at least 4 weeks before joining the trial.

What data supports the effectiveness of the treatment White Blood Cells/Granulocytes for solid cancers?

Research suggests that granulocyte transfusions, which are a type of white blood cell, have shown potential in treating infections in patients with low neutrophil levels (a type of white blood cell important for fighting infections). Additionally, studies indicate that granulocytes may play a role in controlling tumor growth, as seen in experiments with mice, suggesting they could have potential anti-cancer effects.12345

Is white blood cell infusion therapy generally safe for humans?

Research on infusions of natural killer (NK) cells, a type of white blood cell, shows they are generally safe in humans. Studies found that NK cell infusions were well tolerated, with no serious side effects like graft-versus-host disease, and only mild reactions in some cases.678910

How does the treatment of White Blood Cell Infusions for Solid Cancers differ from other treatments?

White Blood Cell Infusions, specifically granulocyte transfusions, are unique because they involve directly infusing white blood cells to help fight infections in patients with low white blood cell counts, unlike traditional cancer treatments that primarily target cancer cells. This approach is particularly beneficial for patients with neutropenia (low levels of neutrophils, a type of white blood cell) who are at high risk for infections, offering a supportive therapy to enhance the body's immune response.111121314

Research Team

DM

Dipnarine Maharaj, MD

Principal Investigator

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

Eligibility Criteria

This trial is for people with solid tumors that are metastatic or unresectable, where standard treatments have failed. Participants must be able to donate white blood cells (granulocytes), have a specific HLA mismatch with the donor, and meet certain health criteria like good organ function and performance status. Pregnant women, those with brain tumors or recent serious illnesses, and individuals on recent immunosuppressants cannot join.

Inclusion Criteria

My cancer is confirmed by tests, cannot be surgically removed, and has spread.
Lesions must be measurable as specified
It has been over 4 weeks since my last medical treatment, radiation, or surgery.
See 4 more

Exclusion Criteria

I do not have uncontrolled diabetes, serious heart conditions, or active infections.
I am of reproductive age and not using effective birth control.
I have been tested for HLA Class I & II antibodies.
See 7 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive granulocyte infusions from healthy donors over a period of 1-2 weeks

1-2 weeks
Up to 5 infusions per week, one infusion per day

Follow-up

Participants are monitored for safety and effectiveness after treatment, with response assessment between Days +90 to +100

3 months

Treatment Details

Interventions

  • White Blood Cells/Granulocytes
Trial OverviewThe study tests if infusing granulocytes from healthy donors can treat cancer. Patients will receive these white blood cells through a process called apheresis after the donors take medications to increase cell production. The treatment spans 1-2 weeks with daily monitoring for side effects, assessing dose response, safety, and effectiveness over three months.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: White Blood Cells/GranulocytesExperimental Treatment1 Intervention
Fresh, non-irradiated granulocytes from ABO-Rh compatible, HLA-mismatched donors

Find a Clinic Near You

Who Is Running the Clinical Trial?

Dipnarine Maharaj

Lead Sponsor

Trials
2
Recruited
60+

Findings from Research

In a study involving 31 patients with acute myeloid leukemia and high-risk lymphoma, repeated infusions of cord blood-derived NK (CB-NK) cells after autologous stem cell transplantation (ASCT) showed promising safety, with only mild infusion reactions occurring in 15.5% of cases.
Patients receiving CB-NK cell therapy had significantly better progression-free survival (PFS) and overall survival (OS) rates compared to a control group, suggesting that this maintenance therapy could effectively reduce relapse rates and improve patient outcomes.
A pilot study of cord blood-derived natural killer cells as maintenance therapy after autologous hematopoietic stem cell transplantation.Wu, Y., Wang, Y., Ji, J., et al.[2023]
The study involved 40 elderly patients with acute myeloid leukemia (AML), showing that donor NK cell infusions are generally safe, with only mild side effects like moderate fever occurring in a few cases after multiple infusions.
High-purity NK cells were successfully expanded and transfused, with no cases of acute graft-versus-host disease (GVHD) observed in elderly AML patients, indicating a promising safety profile for this treatment approach.
[Clinical Safety of NK Cell in the Prevention of Leukemia Relapse Post-transplantation and in Treatment of the Elderly Leukemia Patients].Liu, J., Zheng, XL., Xue, M., et al.[2022]

References

Granulocyte transfusion: a review. [2019]
Granulocyte transfusion therapy. [2017]
Human G-MDSCs are neutrophils at distinct maturation stages promoting tumor growth in breast cancer. [2021]
Murine granulocytes control human tumor growth in SCID mice. [2019]
How are granulocytes for transfusion best used? The past, the present and the future. [2023]
A pilot study of cord blood-derived natural killer cells as maintenance therapy after autologous hematopoietic stem cell transplantation. [2023]
Haploidentical IL-15/41BBL activated and expanded natural killer cell infusion therapy after salvage chemotherapy in children with relapsed and refractory leukemia. [2019]
Safety analysis of ex vivo-expanded NK and NK-like T cells administered to cancer patients: a phase I clinical study. [2020]
Purified donor NK-lymphocyte infusion to consolidate engraftment after haploidentical stem cell transplantation. [2021]
[Clinical Safety of NK Cell in the Prevention of Leukemia Relapse Post-transplantation and in Treatment of the Elderly Leukemia Patients]. [2022]
Granulocyte transfusion therapy for treatment of infections after cytotoxic chemotherapy. [2013]
12.United Statespubmed.ncbi.nlm.nih.gov
G-CSF stimulated donor granulocyte collections for neutropenic sepsis. [2019]
Randomized phase III study of granulocyte transfusions in neutropenic patients. [2022]
Use of G-CSF for granulocyte transfusion therapy. [2019]