Donor MultiTAA-specific T Cells for Leukemia & Preleukemia

Recruiting at 1 trial location

Overseen By Premal Lulla, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: ATG, Campath, Corticosteroids, others

Disqualifiers: Severe infection, GVHD, Pregnant, others

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

Compensation: Varies

Number of Visits: 2

Duration: 4-6 weeks for initial assessment, with additional doses at least 4 weeks apart

44 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study uses special blood cells called multiple tumor-associated antigen (TAA)-specific T cells (a new experimental therapy) to treat patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) which has come back, or may come back, or has not gone away after standard treatment, including an allogeneic hematopoietic stem cell transplant (HSCT). The investigators have previously used this sort of therapy to treat Hodgkin or non-Hodgkin lymphomas that are infected with Epstein-Barr virus (EBV). EBV is found in cancer cells of up to half of all patients with Hodgkin and non-Hodgkin lymphoma. This suggests that it may play a role in causing lymphoma. The cancer cells infected by EBV are able to hide from the body's immune system and escape being killed. The investigators previously tested whether special white blood cells (called T cells) that were trained to kill EBV-infected cells could affect these tumors, and in many patients the investigators found that giving these trained T cells causes a complete or partial response. Other cancers express specific proteins that can be targeted in the same way. The investigators have been able to infuse such tumor-targeted cells into up to 10 patients with lymphoma who do not have EBV, and seen some complete responses. Importantly, the treatment appears to be safe. Therefore, the investigators now want to test whether the investigators can direct these special T cells against other types of cancers that carry similar proteins called tumor-associated antigens (TAAs). These proteins are specific to the cancer cell, so they either do not show up, or show up in low quantities, or normal human cells. The investigators will grow T cells from patients' stem cell donors in the laboratory in a way that will train them to recognize the tumor proteins WT1, NY-ESO-1, PRAME, and Survivin, which are expressed on most AML and MDS cancer cells. The cells will be infused at least 30 days post-allogeneic stem cell transplant. In this study, the investigators want see whether these cells will be able to recognize and kill cancer cells that express these proteins. These donor-derived multiTAA-specific T cells are an investigational product not yet approved by the U.S. Food and Drug Administration The purpose of this study is to find the largest safe dose of donor-derived tumor protein multiTAA-specific T cells for patients with AML or MDS.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on certain treatments like corticosteroids above a specific dose or other investigational cancer therapies within a month before joining the study.

What data supports the effectiveness of the treatment MultiTAA-specific T cells for leukemia and preleukemia?

Research shows that donor-derived T cells targeting specific leukemia antigens can help prevent relapse in patients with acute lymphoblastic leukemia (ALL) after a stem cell transplant. In a study, most patients who received these T cells remained in long-term remission, suggesting this treatment may help control the disease. ^{1 2 3 4 5}

Is the treatment with donor-derived multiTAA-specific T cells safe for humans?

Research indicates that donor-derived multiTAA-specific T cells have been administered to patients with leukemia without causing serious side effects like graft-versus-host disease (a condition where donor cells attack the recipient's body) or cytokine release syndrome (a severe immune reaction). This suggests that the treatment is generally safe in humans. ^{1 2 4 5 6}

How is the treatment MultiTAA-specific T cells unique for leukemia and preleukemia?

MultiTAA-specific T cells are unique because they are derived from a donor and specifically target multiple tumor-associated antigens found in leukemia cells, aiming to prevent relapse after a stem cell transplant. This approach enhances the immune system's ability to fight leukemia while minimizing the risk of graft-versus-host disease, a common complication in similar treatments. ^{1 2 3 4 7}

Research Team

Premal Lulla, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who have had a stem cell transplant but still show signs of the disease. Participants need to have a compatible donor, stable vital signs, and agree to use effective birth control. They can't join if they've recently received certain immune therapies, are pregnant, have severe infections or GVHD above Grade II.

Inclusion Criteria

Hgb ≥ 7.0 g/dL (can be transfused)

Pulse oximetry of > 90% on room air

My tests show remaining cancer cells after treatment.

Exclusion Criteria

Pregnant or lactating

I am scheduled to receive a T cell infusion within 4 weeks after getting a Donor Lymphocyte Infusion.

I had a stem cell transplant from a donor less than 30 days ago.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravenous infusion of donor-derived multiTAA-specific T cells, with potential for up to six additional doses if no change or reduction in cancer cells is observed

4-6 weeks for initial assessment, with additional doses at least 4 weeks apart

1 visit for initial infusion, additional visits for subsequent doses

Follow-up

Participants are monitored for safety and effectiveness after treatment, with blood tests and assessments at various intervals

1 year

Regular visits at weeks 1, 2, 4, 8, and months 3, 6, 9, 12

Long-term follow-up

Participants are contacted annually to evaluate long-term disease response

4 additional years

Treatment Details

Interventions

• MultiTAA-specific T cells

Trial Overview The study tests multiTAA-specific T cells from donors as an experimental therapy for AML/MDS after standard treatments fail. It aims to find the highest safe dose of these cells that can recognize and kill cancer cells expressing specific proteins.

Participant Groups

Group I: Group B Experimental Treatment 1 Intervention

Treatment with donor-derived multiTAA-specific T cells for relapsed/residual disease following HSCT for AML or MDS

Group II: Group A Experimental Treatment 1 Intervention

Treatment with donor-derived multiTAA-specific T cells as adjuvant therapy following HSCT for AML or MDS

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

American Society for Blood and Marrow Transplantation (ASBMT)

Collaborator

Trials

1

Recruited

40+

Cancer Prevention Research Institute of Texas

Collaborator

Trials

55

Recruited

98,900+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

Findings from Research

Infusing donor-derived multiple leukemia antigen-specific T cells (mLSTs) into 11 patients with high-risk acute lymphoblastic leukemia (ALL) was found to be safe, with no dose-limiting toxicity or acute graft-versus-host disease (GVHD) observed.

Of the evaluable patients, 6 out of 8 remained in long-term complete remission, suggesting that mLST infusion may enhance disease control by promoting in vivo T-cell expansion against leukemia antigens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donor-derived multiple leukemia antigen-specific T-cell therapy to prevent relapse after transplant in patients with ALL. Naik, S., Vasileiou, S., Tzannou, I., et al.[2023]

Injecting T lymphocytes from a matched donor can effectively cure chemotherapy-resistant blood cancers, demonstrating a strong immune response against tumors, primarily through T cells targeting specific minor histocompatibility antigens.

Recent research indicates that using primed T cells that target a specific minor histocompatibility antigen can eliminate leukemia cells without causing harmful side effects, suggesting a safer approach to T cell immunotherapy for cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive cancer immunotherapy: discovering the best targets. Perreault, C., Brochu, S.[2011]

Adoptive transfer of genetically engineered T cells has shown significant and lasting responses in patients with blood cancers, highlighting its potential as a powerful treatment option.

The success of this therapy relies heavily on the quality of T cells produced, which is influenced by the methodologies and reagents used in their generation for preclinical studies, particularly in the context of chimeric antigen receptor T cell therapy for acute myeloid leukemia (AML).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generating and Expanding Autologous Chimeric Antigen Receptor T Cells from Patients with Acute Myeloid Leukemia. Kenderian, SS., June, CH., Gill, S.[2018]

Adoptive transfer of donor-derived T-cells, specifically those sensitized to minor alloantigens or leukemia-specific proteins like WT-1, shows promise as a treatment strategy for preventing EBV lymphomas and cytomegalovirus infections after allogeneic hematopoietic cell transplants.

Current evidence from preclinical studies and initial clinical trials highlights both the potential effectiveness of this approach and the limitations that need to be addressed for successful implementation in leukemia treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive transfer of unselected or leukemia-reactive T-cells in the treatment of relapse following allogeneic hematopoietic cell transplantation. O'Reilly, RJ., Dao, T., Koehne, G., et al.[2023]

Genetically engineered T cells that express a CD19-specific chimeric immunoreceptor can effectively target and eradicate B-lineage malignancies, showcasing a promising approach in cancer treatment.

Using these modified T cells can potentially avoid the complications of graft-versus-host disease (GVHD) associated with traditional donor-derived T cell therapies, enhancing the safety and efficacy of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and application of CD19-specific T cells for adoptive immunotherapy of B cell malignancies. Cooper, LJ., Al-Kadhimi, Z., DiGiusto, D., et al.[2007]

In a first-in-human trial involving 10 heavily pre-treated patients with relapsed or metastatic breast cancer, multi-antigen-targeted T cells (multiTAA-T) were well tolerated with no treatment-related toxicities, indicating a promising safety profile for this therapy.

One patient experienced prolonged disease stabilization for 5 months, which was linked to the in vivo expansion and persistence of T cells targeting specific tumor antigens, along with evidence of broader immune activation against non-targeted tumor antigens in 7 out of 10 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer. Hoyos, V., Vasileiou, S., Kuvalekar, M., et al.[2022]

Leukemia-associated antigens (LAAs) can be targeted by adoptive T cell therapies, where CD8(+) T cells with specific T cell receptors are selected and infused into leukemia patients to attack leukemic cells.

Streptamers are a GMP-certified technology used for sorting these antigen-specific T cells, making it a reliable method for enhancing immune responses in patients with leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted cellular immunotherapy for leukemia patients. Casalegno-Garduño, R., Schmitt, A., Wang, X., et al.[2010]

References

1. United States pubmed.ncbi.nlm.nih.gov

Donor-derived multiple leukemia antigen-specific T-cell therapy to prevent relapse after transplant in patients with ALL. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Adoptive cancer immunotherapy: discovering the best targets. [2011]

3. United States pubmed.ncbi.nlm.nih.gov

Generating and Expanding Autologous Chimeric Antigen Receptor T Cells from Patients with Acute Myeloid Leukemia. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Adoptive transfer of unselected or leukemia-reactive T-cells in the treatment of relapse following allogeneic hematopoietic cell transplantation. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Development and application of CD19-specific T cells for adoptive immunotherapy of B cell malignancies. [2007]

6. England pubmed.ncbi.nlm.nih.gov

Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Targeted cellular immunotherapy for leukemia patients. [2010]