Veto Cell Therapy for Leukemia and Lymphoma

Overseen By Richard E Champlin

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: HIV, Uncontrolled infection, CNS malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using cytokine-treated veto cells, a type of cell therapy, to assist patients with certain blood cancers and severe blood disorders after a stem cell transplant. The goal is to determine if these special cells can help the donor's stem cells grow in the patient’s body without causing graft-versus-host disease, where the new cells attack the patient's body. Suitable candidates include those with blood cancers like leukemia or lymphoma who have had mixed results with chemotherapy, or those with sickle cell disease experiencing severe symptoms. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that cytokine-treated veto cells are likely to be safe for humans?

Research has shown that special cells, called cytokine-treated veto cells, might be safe for patients. In studies, these cells did not cause graft-versus-host disease (GVHD), a condition where donor cells attack the patient's body. This suggests the treatment is well-tolerated.

Other research has demonstrated strong effects of these veto cells against tumors in lab and animal studies, without harmful reactions. This increases confidence in their safety for human use.

Although this trial remains in the early stages, these findings offer hope that cytokine-treated veto cells could be a safe option for patients with blood cancers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for leukemia and lymphoma, which often rely on chemotherapy and radiation, cytokine-treated Veto Cells offer a novel approach by using modified immune cells to target cancer. These Veto Cells are designed to prevent the rejection of transplanted cells and to minimize the risk of graft-versus-host disease (GVHD), a common complication of bone marrow transplants. Researchers are excited about this treatment because it aims to enhance the efficacy of the transplant while reducing potential side effects, offering a more targeted and potentially safer option for patients.

What evidence suggests that cytokine-treated veto cells might be an effective treatment for leukemia and lymphoma?

Research has shown that special cells treated with cytokines, which participants in this trial will receive, may improve the success of stem cell transplants for blood cancers like leukemia and lymphoma. Studies in mice found that these cells can help donor stem cells settle in better by calming the host's immune system, which might otherwise reject the transplant. This can lead to a successful transplant without causing a condition where donor cells attack the recipient's body. Early results suggest that these cells might help patients restore healthy blood cell production after a transplant. While research in humans continues, strong evidence from animal studies supports this approach. ^{1 2 3 4 5}

Who Is on the Research Team?

Richard E. Champlin

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients aged 12-75 with various blood cancers or bone marrow failure who've had persistent disease despite treatment. They must have a certain level of physical fitness, organ function, and a compatible family donor. Excluded are those with cognitive impairments, uncontrolled conditions, HIV, active brain cancer, or an available matched stem cell donor.

Inclusion Criteria

I am able to care for myself but may not be able to do active work.

I have a related donor aged 12-70 who is a partial genetic match.

You must have a lung function test that shows your lungs are working at least 50% as well as expected for your age and gender.

Exclusion Criteria

I have an active brain or spinal cord tumor.

I do not have any severe infections or health/mental conditions that could affect my treatment.

Individuals with cognitive impairments and/or any serious unstable pre-existing condition or psychiatric disorder that can interfere with safety or without obtaining informed consent or compliance with study procedures

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Regimen

Patients receive anti-thymocyte globulin (ATG) and fludarabine, followed by total body irradiation (TBI)

9 days

Daily visits for treatment administration

Transplant

Patients undergo peripheral blood stem cell transplantation (PBSCT)

1 day

1 visit (in-person)

GVHD Prophylaxis

Patients receive cyclophosphamide and cytokine-treated veto cells to prevent graft-versus-host disease

7 days

Multiple visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Weekly visits for 4 weeks, monthly for 3 months, then periodically

What Are the Treatments Tested in This Trial?

Interventions

• Cytokine-treated Veto Cells

Trial Overview

The study tests if cytokine-treated veto cells can help patients accept stem cells from family donors without developing graft-versus-host-disease after receiving chemotherapy and total-body irradiation to wipe out cancerous and normal blood-forming cells.

How Is the Trial Designed?

Group I: Treatment (chemotherapy, PBSCT, cytokine-treated veto cells) Experimental Treatment 6 Interventions

CONDITIONING REGIMEN: Patients receive ATG IV over 4 hours on days -9 to -7, and fludarabine IV over 1 hour on days -6 to -3, then undergo TBI on day -1. TRANSPLANT: Patients undergo PBSCT IV over 30-60 minutes on day 0. GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 3 hours on days +3 and +4 and cytokine-treated veto cells IV over 30-60 minutes on day +7.

Cytokine-treated Veto Cells is already approved in United States for the following indications:

Approved in United States as Cytokine-Treated Veto Cells for:

• Hematologic malignancies following stem cell transplant

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

In a phase I clinical trial involving three patients with B-cell lineage acute lymphoblastic leukemia, CAR-T-19 therapy led to significant clinical responses, including one patient achieving a 9-week sustained complete remission before undergoing a stem cell transplant.

Persistent functional activity of CAR-T-19 cells was indicated by long-term increases in serum cytokines, suggesting that these cells may enhance the effectiveness of subsequent chemotherapy in patients who experience relapse after initial CAR-T-19 treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An analytical biomarker for treatment of patients with recurrent B-ALL after remission induced by infusion of anti-CD19 chimeric antigen receptor T (CAR-T) cells. Zhang, Y., Zhang, W., Dai, H., et al.[2017]

Administration of anti-IL-2 receptor monoclonal antibodies or chimeric IL-2 toxins can effectively target activated lymphocytes for immunosuppression, showing promise in treating IL-2R+ leukemia and lymphoma.

Preliminary evidence from open studies suggests that chimeric IL-2 toxins are well tolerated and may improve conditions in patients with IL-2R+ leukemia/lymphoma, as well as in those with refractory rheumatoid arthritis or new-onset diabetes mellitus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin-2 receptor-directed therapies: antibody-or cytokine-based targeting molecules. Strom, TB., Kelley, VR., Murphy, JR., et al.[2021]

In a study involving 9 patients (5 with non-Hodgkin's lymphoma and 4 with chronic lymphocytic leukaemia), treatment with the monoclonal antibody Campath-1H led to significant tumor regression in peripheral blood and bone marrow, although lymph nodes were less affected.

The therapy resulted in a profound reduction of normal B and T cells, while a notable expansion of CD8+ T cells occurred in some patients, suggesting these clonal T cells may play a role in controlling tumor growth and could be a target for future immune therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clonal CD8+ and CD52- T cells are induced in responding B cell lymphoma patients treated with Campath-1H (anti-CD52). Osterborg, A., Werner, A., Halapi, E., et al.[2019]

Interleukin-2 (IL-2) shows promise in treating certain cancers, particularly in prolonging remission and preventing relapse in leukemia patients with minimal tumor load, as it can activate immune cells to target residual cancer cells.

Current research is exploring various strategies to enhance IL-2's effectiveness, including combining it with monoclonal antibodies and other cytokines to improve tumor destruction and overall antitumor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospects for interleukin-2 therapy in hematologic malignant neoplasms. Malkovska, V., Sondel, PM.[2007]

A new culture protocol successfully activated and proliferated tumor-infiltrating T lymphocytes (TIL) from eight patients with indolent non-Hodgkin's lymphoma, leading to a significant increase in CD8+ T lymphocytes in 6 out of 8 cases.

The expanded CD8+ T lymphocytes demonstrated specific cytotoxicity against autologous malignant B cells, indicating that this method can effectively generate antitumor-specific cytotoxic T cells using a combination of cytokines and irradiated tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differentiation of antitumor-specific cytotoxic T lymphocytes from autologous tumor infiltrating lymphocytes in non-Hodgkin's lymphomas. Chaperot, L., Delfau-Larue, MH., Jacob, MC., et al.[2019]

The study evaluated an immunotherapy regimen combining rIL-2, rIFN-alpha, and histamine in a patient with relapsing aggressive non-Hodgkin's lymphoma, showing significant increases in T-cell responses and natural killer (NK) cell activity during chemotherapy-induced remission.

The treatment led to enhanced production of key cytokines (IFN-gamma, IL-4, and TNF-alpha) by T-cells, indicating a robust immune response, while also reducing potentially regulatory lymphocytes, suggesting a promising approach to boost immune function in lymphoma patients post-chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stimulation of T-cell cytokine production and NK-cell function by IL-2, IFN-alpha and histamine treatment during remission of non-Hodgkin's lymphoma. Ahlberg, R., MacNamara, B., Andersson, M., et al.[2016]

In patients with chronic lymphocytic leukemia (CLL), CAR T cells that successfully induced remission were characterized by memory-related gene expression, particularly involving IL-6/STAT3 pathways, while nonresponders showed signs of T cell exhaustion and differentiation.

The presence of CD27+CD45RO-CD8+ T cells with memory-like traits before CAR T cell therapy was linked to better outcomes, suggesting that identifying these biomarkers could enhance the effectiveness of immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia. Fraietta, JA., Lacey, SF., Orlando, EJ., et al.[2021]

Blocking or knocking out IFNγ does not impair the effectiveness of CAR T cells against hematologic malignancies, suggesting that IFNγ is not essential for their antitumor activity.

In fact, IFNγ blockade can enhance CAR T cell proliferation and reduce macrophage activation, potentially decreasing the risk of cytokine release syndrome (CRS) while maintaining treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blockade or Deletion of IFNγ Reduces Macrophage Activation without Compromising CAR T-cell Function in Hematologic Malignancies. Bailey, SR., Vatsa, S., Larson, RC., et al.[2023]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12126084/

Anti-viral CD8 central memory veto cells as a new platform for ...

Central memory CD8 T cells exhibit marked veto activity enhancing engraftment in several mouse models of T cell-depleted bone marrow (TDBM) allografting.

2.

astctjournal.org

astctjournal.org/article/S2666-6367(23)01638-X/fulltext

Generation of Non-Alloreactive Antiviral Central Memory ...

Here we describe 2 alternative methodologies for generating antiviral CD8 veto cells for a first in-human clinical trial.

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0006497123114340

Allogeneic Veto-CAR CD8 T Cells Enabling Prolonged ...

Studies in mice have demonstrated that CD8 T cells exhibit marked veto activity against host T cells with anti-graft specificity, enhancing engraftment.

4.

mdanderson.org

mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2018-0221.html

Anti-viral Central Memory CD8 Veto Cells in Haploidentical ...

This phase I/II trial studies how well cytokine-treated veto cells work in treating patients with hematologic malignancies following stem cell transplant.

5.

clinicaltrial.be

clinicaltrial.be/en/details/67721?per_page=100&only_recruiting=0&only_eligible=0&only_active=0

Cytokine-Treated Veto Cells in Treating Patients With Hem...

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