Donor MultiTAA-specific T Cells for Leukemia & Preleukemia

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using special blood cells called multiTAA-specific T cells (donor-derived multiple tumor-associated antigen-specific T cells) to combat acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), particularly when these conditions persist or return after other treatments. Researchers cultivate these T cells in a lab to enable them to recognize and destroy cancer cells. The trial aims to determine the largest safe dose for this treatment. Suitable participants have undergone a stem cell transplant and still show signs of AML or MDS. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that multiTAA-specific T cells have been tested in people with various types of lymphoma. These T cells have proven safe, with many patients experiencing tumor reduction or disappearance. This treatment trains special blood cells to target proteins found only in cancer cells.

In a small group of patients without the Epstein-Barr virus, some achieved complete responses, and the treatment remained safe. The researchers aim to determine if these T cells can also combat other cancers, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

So far, the treatment has not caused serious harm. However, it remains under study and lacks FDA approval for AML or MDS. This study focuses on identifying the largest safe dose for patients. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for leukemia?

Unlike the standard treatments for leukemia and preleukemia, which often involve chemotherapy and stem cell transplants, donor-derived MultiTAA-specific T cells offer a targeted approach. These T cells are engineered to specifically recognize and attack multiple tumor-associated antigens present in cancer cells, which could potentially enhance effectiveness and reduce side effects. Researchers are excited because this method harnesses the body's immune system to fight cancer more precisely, possibly leading to better outcomes with fewer complications compared to traditional therapies.

What evidence suggests that this treatment might be an effective treatment for leukemia and preleukemia?

Research has shown that multiTAA-specific T cells can locate and destroy cancer cells by identifying proteins unique to these cells. These proteins, known as tumor-associated antigens (TAAs), appear on many cancer cells, including those in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). In this trial, participants will receive donor-derived multiTAA-specific T cells either as adjuvant therapy following hematopoietic stem cell transplantation (HSCT) or for relapsed/residual disease. Previous treatments using similar T cells for lymphomas have shown encouraging results, with some patients experiencing full or partial recovery. Although data for AML and MDS is limited, this method aims to harness the body's immune system to target and fight cancer more precisely and effectively. Early results suggest this therapy could enhance the graft-versus-leukemia effect, aiding the body in attacking cancer cells after stem cell transplants. ^{1 3 6 7 8}

Who Is on the Research Team?

Premal Lulla, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02494167

Administration of Donor Multi TAA-Specific T Cells for AML ... 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. Detailed ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9290161/

Multi-antigen-targeted T-cell therapy to treat patients with ... Of the 10 heavily pre-treated patients enrolled and infused with multiTAA T cells, nine had disease progression while one patient with 10 lines ...

3. markertherapeutics.com markertherapeutics.com/wp-content/uploads/ISCT2022_Poster_Clinical_MK_042022_FINAL.pdf

MT-401 (multi-tumor-associated antigen-specific T cells) ... Using multi-tumor-associated antigen (multi-TAA)-specific T-cells can potentially enhance the GVL effect while simultaneously mitigating the risk of inducing.

4. withpower.com withpower.com/trial/phase-1-leukemia-myeloid-1-2016-7fd7b

Donor MultiTAA-specific T Cells for Leukemia & 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, ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04511130

NCT04511130 | Efficacy of MT-401 in Patients With AML ... MT-401 (zedenoleucel) is an allogeneic multi-tumor-associated antigen (MultiTAA)-specific T cell product manufactured under Good Manufacturing Practice (GMP) ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04511130

NCT04511130 | Efficacy of MT-401 in Patients With AML ... This study is a Phase 2 multicenter study with a Safety Lead-in evaluating safety and efficacy of MT-401 administration to patients with AML, ...

7. ir.markertherapeutics.com ir.markertherapeutics.com/news-releases/news-release-details/marker-therapeutics-reports-non-clinical-proof-concept-data-and

Press Releases “We recently developed this long-term in vitro model to monitor the interaction of cancer cells with multiTAA-specific T cells and to further ...

8. ir.markertherapeutics.com ir.markertherapeutics.com/news-releases/news-release-details/marker-therapeutics-reports-mt-401-non-clinical-data-aml-cells

Marker Therapeutics Reports MT-401 Non-Clinical Data in ... The multiTAA-specific T cell technology from Marker uses a novel non-genetically modified T cell therapy approach that recognizes multiple ...