Engineered T Cells for Blood Cancer

(RESOLVE Trial)

Recruiting at 3 trial locations

Overseen By Fahmida Hoq, MBBS, MS

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Catherine Bollard

Must not be taking: PD-1 inhibitors

Disqualifiers: Uncontrolled infections, Active GVHD, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 5 months

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a new treatment using engineered T cells, a type of immune cell, to combat high-risk blood cancers like AML and MDS. Known as Tumor Associated Antigen Lymphocytes (TAA-T), the treatment involves infusing these specialized cells after a stem cell transplant to determine if they can safely help prevent cancer relapse. Suitable candidates have high-risk AML or MDS, have undergone a stem cell transplant, and are managing their condition without a relapse. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance 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 if you need to stop taking your current medications. However, certain medications like PD-1 inhibitors or other T cell activating agents are excluded for some participants, and investigational therapies are not allowed within 28 days prior to the infusion.

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

Research has shown that tumor-associated antigen lymphocytes (TAA-T) are generally safe for humans. Studies have demonstrated that these T cells are well-tolerated in treating various cancers. For instance, one study found that TAA-T cells in patients with Hodgkin lymphoma did not cause significant side effects. Another study confirmed these findings, indicating that TAA-T infusions are safe and may help treat certain virus-related cancers.

Since this trial is in its early stages, the main goal is to test the treatment's safety. Early trials often focus on assessing how well people tolerate the treatment and identifying any initial safety concerns. So far, evidence suggests that TAA-T cells show promise in terms of safety for treating blood cancers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for blood cancer, which often include chemotherapy and radiation, Tumor Associated Antigen Lymphocytes (TAA-T) offer a more targeted approach. TAA-T is unique because it involves engineering T cells to specifically recognize and attack cancer cells by targeting tumor-associated antigens. This precision reduces damage to healthy cells, potentially leading to fewer side effects. Researchers are excited about TAA-T because it leverages the body's own immune system to fight cancer, opening the door to more personalized and effective therapies.

What evidence suggests that TAA-T might be an effective treatment for blood cancer?

Research has shown that a type of immune cell, called TAA-T cells, could help treat certain cancers. These specially designed cells can find and destroy cancer cells by recognizing specific proteins on them. In this trial, participants will receive TAA-T cells after neutrophil engraftment post-HSCT or on day 30, whichever comes first. In past studies, patients with Hodgkin lymphoma who received TAA-T cells along with nivolumab found it safe, and the TAA-T cells remained active in their bodies. Research also indicates that these T cells can effectively treat cancers linked to viruses, like some forms of Hodgkin's disease. Early results suggest that the more tumor-related proteins a patient has, the better these T cells might work. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for people aged 6 months to 80 years with certain high-risk blood cancers or tumors who have had, or will have, a stem cell transplant. They must be in relatively good health otherwise and agree to use contraception if applicable. Pregnant women, those with severe graft-versus-host disease (GVHD), uncontrolled infections, or recent treatment with certain immune therapies are excluded.

Inclusion Criteria

I am between 6 months and 80 years old.

Agree to use contraceptive measures during study protocol participation

I (or my guardian) can understand and agree to the study's terms.

Exclusion Criteria

I do not have any infections that are not responding to treatment.

Pregnancy or lactating (female of childbearing potential)

No investigational therapies within 28 days prior to TAA-T infusion

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tumor multi-antigen associated specific cytotoxic T lymphocytes (TAA-T) with dose escalation to evaluate safety and efficacy

5 months

Multiple infusions based on dose level and response

Follow-up

Participants are monitored for safety, including acute GVHD and other adverse events, and effectiveness after TAA-T infusion

1 year

Long-term follow-up

Event-free and overall survival are assessed, and incidence and severity of GVHD are monitored

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Tumor associated antigen lymphocytes (TAA-T)

Trial Overview The study tests TAA-T cells in patients receiving stem cell transplants for aggressive blood cancers. It's divided into three arms: A) post-transplant patients; B) pre-transplant patients; C) post-transplant without relapse. The goal is to see if these cells improve survival without the cancer returning after six months.

How Is the Trial Designed?

Group I: Tumor associated antigen lymphocytes (TAA-T) Experimental Treatment 1 Intervention

TAA-T will be infused any time after neutrophil engraftment post-HSCT or day 30, whichever comes first. All infusions will be within 5 months post-HSCT. Patients will receive a TAA-T cell dose of 4 x 107 cells/m2.

Who Is Running the Clinical Trial?

Catherine Bollard

Lead Sponsor

Trials

13

Recruited

290+

Children's National Research Institute

Collaborator

Trials

227

Recruited

258,000+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Published Research Related to This Trial

The study by Schmitt et al. explores the biology and safety of T cells that have been genetically modified to express T-cell receptor (TCR) variants, which have a stronger ability to recognize tumor-associated antigens.

These engineered T cells show promise for improving cancer immunotherapy by potentially enhancing the effectiveness of the immune response against tumors while maintaining safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trick to treat: tricking the thymus to treat cancer. Bonini, C., Mondino, A.[2021]

In a first-in-human trial involving 15 patients with relapsed or refractory solid tumors, tumor-associated antigen cytotoxic T cells (TAA-Ts) were administered safely without any dose-limiting toxicities, demonstrating a promising new therapeutic approach.

Of the evaluable patients, 73% showed stable disease or better at day 45 post-infusion, with 6 patients remaining progression-free for a median of 13.9 months, indicating that TAA-Ts can effectively stabilize disease and prolong time to progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy of Relapsed and Refractory Solid Tumors With Ex Vivo Expanded Multi-Tumor Associated Antigen Specific Cytotoxic T Lymphocytes: A Phase I Study. Hont, AB., Cruz, CR., Ulrey, R., et al.[2020]

Adoptive T-cell therapy using tumor-infiltrating lymphocytes (TILs) has shown significant promise in treating metastatic melanoma, leading to the development of genetically engineered T cells that can specifically target tumor-associated antigens (TAAs).

Initial clinical studies indicate that these genetically engineered T cells, including those with tumor antigen-specific T cell receptors (TCRs) and chimeric antigen receptors (CARs), can effectively cause tumor regression, although safety concerns, particularly regarding potential 'on-target, off-organ' toxicity, must be carefully managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving the efficacy and safety of engineered T cell therapy for cancer. Shi, H., Liu, L., Wang, Z.[2020]

In a study involving 9 patients with acute myeloid leukemia (AML) at high risk of relapse, the infusion of tumor-associated antigen-specific cytotoxic T lymphocytes (TAA-CTLs) showed promising safety, with no significant adverse reactions reported during or after treatment.

The TAA-CTL therapy demonstrated an antileukemic effect in 2 out of 5 patients who were minimal residual disease (MRD) positive, indicating potential efficacy in reducing leukemia without the need for additional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T cells targeting multiple tumor-associated antigens as a postremission treatment to prevent or delay relapse in acute myeloid leukemia. Xue, L., Hu, Y., Wang, J., et al.[2022]

Engineered T cells expressing T-cell receptors (TCRs) can specifically target tumor-associated antigens (TAAs), making them a promising approach in cancer treatment, particularly for hematologic malignancies.

Current early-phase clinical trials are testing TCR-T therapies targeting three different TAAs, while preclinical studies are exploring many more, indicating a broad potential for safe and effective cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-Cell Receptor-Based Immunotherapy for Hematologic Malignancies. Biernacki, MA., Brault, M., Bleakley, M.[2023]

T-cell immunotherapy has emerged as a powerful treatment for blood cancers, leveraging the graft-vs.-leukemia (GVL) effect, which relies on recognizing histocompatibility antigens between donors and recipients.

Modern genomics and proteomics are enabling the identification of tumor-specific and tumor-associated antigens, which can enhance the effectiveness of T-cell therapies by targeting multiple blood neoplasms, thus overcoming limitations seen in other immunotherapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-Cell Immunotherapies Targeting Histocompatibility and Tumor Antigens in Hematological Malignancies. Janelle, V., Rulleau, C., Del Testa, S., et al.[2021]

Tumor-associated antigen-specific cytotoxic T lymphocytes (TAA-CTL) were safely generated and infused into patients with multiple myeloma and non-Hodgkin lymphoma, with no significant adverse reactions reported during the treatment.

In a small group of 7 patients, TAA-CTL therapy showed promising efficacy, as 5 patients experienced positive clinical effects, and an increase in specific immune responses was observed 2-3 weeks post-infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Research of Dendritic Cell-Mediated Tumor-Associated Antigen-Specific Cytotoxic T Lymphocytes in the Treatment of Multiple Myeloma and Non-Hodgkin Lymphoma]. Li, XH., Xue, L., Xu, H., et al.[2020]

The study focuses on creating antigenic peptides from tumor-associated antigens (TAA) to develop effective cancer vaccines.

These antigenic peptides are designed to stimulate cytotoxic T lymphocytes (CTL), which are crucial for targeting and destroying cancer cells, and the effectiveness of this CTL induction is validated in the research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Production of multiple CTL epitopes from multiple tumor-associated antigens. Morita, R., Hirohashi, Y., Nakatsugawa, M., et al.[2014]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8791594/

Tumor-associated antigen–specific T cells with nivolumab ... Tumor-associated antigen–specific T cells with nivolumab are safe and persist in vivo in relapsed/refractory Hodgkin lymphoma.

2. astctjournal.org astctjournal.org/article/S1083-8791(09)00682-X/fulltext

Multi-Tumor-Antigen-Specific Cytotoxic T Lymphocytes For ... Tumor immunotherapy using in vitro expanded cytotoxic T lymphocytes (CTLs) can effectively treat virus-associated malignancies such as EBV +ve Hodgkin's ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6642655/

T cells targeting multiple tumor-associated antigens as a ... The results showed that infusion of autologous tumor-associated antigen-specific cytotoxic T lymphocytes (TAA-CTLs) is safe and can provide ...

4. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/50/NCT03093350/Prot_SAP_000.pdf

TUMOR-ASSOCIATED ANTIGEN (TAA)-SPECIFIC ... This study will evaluate the clinical efficacy of T cells specific for all 5 tumor associated antigens in a fixed dose study. 6.1 Dose Levels. The patients ...

5. aacrjournals.org aacrjournals.org/cancerimmunolres/article/12/11/1589/749294/Tumor-Associated-Antigen-Burden-Correlates-with

Tumor-Associated Antigen Burden Correlates with Immune ... The authors demonstrate that tumor-associated antigen burden correlates with the efficacy of immune checkpoint inhibition in patients with tumor mutation.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02203903

Study Details | NCT02203903 | Multi-institutional ... This Phase I dose-escalation trial is designed to evaluate the safety of administering rapidly -generated tumor multi-antigen associated -specific cytotoxic T ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05238792

NCT05238792 | Multi Tumor-Associated Antigen-Specific T ... This is a phase I dose-escalation study to evaluate the safety of partially human leukocyte antigen (HLA)-matched multi tumor-associated antigen-specific T ...