TAA-Specific CTL Therapy for Lymphoma

(TACTAL Trial)

Not currently recruiting at 1 trial location

Overseen By George Carrum, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must be taking: Azacytidine

Must not be taking: Systemic corticosteroids

Disqualifiers: Severe infection, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: 10

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with Hodgkin or non-Hodgkin lymphoma, particularly for those whose cancer has returned or resisted standard treatments. The treatment uses special immune cells, called T cells, trained in the lab to target cancer-specific proteins known as tumor-associated antigens (TAAs). This method is called TAA-Specific CTL Therapy. Some patients will also receive a drug called azacytidine to determine if it enhances the T cells' effectiveness. Suitable candidates include those with long-standing lymphoma, especially if it has recurred or not responded to regular treatment. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that participants stop taking conventional therapy, including rituximab, at least one week before joining the study. Additionally, participants should not be on other investigational therapies for one month prior to the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that treatments using special T cells, known as tumor-associated antigen (TAA)-specific cytotoxic T lymphocytes (CTLs), are generally safe. Past studies have tested these T cells to determine their ability to safely target cancer cells. Results suggest that these T cells are well-tolerated, with few serious side effects.

For the study involving azacytidine and multiTAA T cells, previous research has shown that combining azacytidine, a chemotherapy drug, with TAA-specific T cells is usually safe. Most patients did not experience severe side effects from this combination.

In the dose-escalation stage, studies have safely tested increasing doses of T cell therapies in similar trials. This process helps identify the right dose that is both effective and safe for patients.

For younger patients, research with multiTAA-specific T cells indicates that these treatments are safe and can be administered without major issues. This suggests the therapy is well-tolerated by children and teens.

Overall, while this is an early phase trial, evidence from similar treatments suggests that the therapy is likely safe for participants. The main goal is to find the best dose that minimizes side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for lymphoma because they involve innovative approaches using TAA-specific cytotoxic T lymphocytes (CTLs). Unlike standard chemotherapy and radiation therapies, which can affect both healthy and cancerous cells, these treatments focus on boosting the body's immune response specifically against tumor-associated antigens (TAAs). The antigen-escalation stage explores the potential of CTLs to target multiple specific antigens, potentially leading to a more precise attack on cancer cells. Meanwhile, the combination of azacytidine with multiTAA T cells aims to enhance the immune response by encouraging epitope spreading, where more diverse antigens are targeted by the immune system. Additionally, the pediatric stage provides a tailored approach for young patients, focusing on safety and effectiveness for children with active Hodgkin's or non-Hodgkin's lymphoma.

What evidence suggests that this trial's treatments could be effective for lymphoma?

Research has shown that using special immune cells called T cells to target specific proteins on cancer cells might help treat lymphoma. In earlier studies, T cells trained to attack cells infected with the Epstein-Barr virus (EBV) showed promising results, with many patients experiencing complete or partial recovery from Hodgkin and non-Hodgkin lymphomas. However, since not all lymphoma cases are linked to EBV, researchers are now investigating T cells that target proteins unique to cancer cells, which could offer similar benefits.

In this trial, some patients will participate in the azacytidine and multiTAA T cells stage, receiving a drug called azacytidine, which might enhance the effectiveness of T cell therapy. Previous studies with azacytidine have shown good results in similar treatments, suggesting it could boost the T cells' ability to fight cancer. Overall, using these specialized T cells, possibly combined with azacytidine, shows promise in treating lymphoma by focusing on important cancer cell proteins. ^{6 7 8 9 10}

Who Is on the Research Team?

Geoge Carrum, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for adults and children with Hodgkin or non-Hodgkin lymphoma that has returned after treatment, hasn't responded to treatment, or as a second cancer. Participants need a certain level of hemoglobin, normal organ function tests, and must not be pregnant. They should not have severe infections, HIV, hepatitis B/C infection or be on systemic steroids.

Inclusion Criteria

PROCUREMENT: Life expectancy of 6 weeks or greater

PROCUREMENT: Patient and/or parent/guardian able to give informed consent

TREATMENT: Patients should have been off other investigational therapy for one month prior to entry in this study

Exclusion Criteria

PROCUREMENT: Patients with active HIV infection at time of procurement (can be pending at the time of blood draw)

I am currently taking corticosteroids.

TREATMENT: Abnormal coagulation parameters (PT greater than 15 seconds, PTT greater than 40 seconds, and/or INR greater than 1.5)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Antigen-Escalation

Patients receive TAA-specific T cells targeting increasing numbers of TAAs to evaluate safety

8 weeks

2 infusions, 28 days apart

Dose-Escalation

Patients receive increasing doses of T cells to evaluate safety

6 weeks

2 infusions, 14 days apart

Aza Stage

Adult patients receive azacytidine followed by T cell infusions to test combination therapy

3 months

3 cycles of aza, 2 T cell infusions

Pediatric Stage

Pediatric patients receive T cell infusions to test safety and efficacy

2 weeks

2 infusions, 14 days apart

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Regular blood tests and imaging studies

Long-term Follow-up

Annual follow-up to evaluate disease response long-term

4 years

What Are the Treatments Tested in This Trial?

Interventions

• Antigen-Escalation Stage
• azacytidine and multiTAA T cells Stage
• Dose-Escalation Stage
• Pediatric multiTAA T cells Stage

Trial Overview The study is testing TAA-specific cytotoxic T lymphocytes (CTLs), which are immune cells designed to target proteins commonly found on lymphoma cells. Some adult patients will also receive azacytidine before the CTLs to potentially enhance the effectiveness of the therapy.

How Is the Trial Designed?

Group I: azacytidine and multiTAA T cells Stage Experimental Treatment 1 Intervention

This phase will administer aza intravenously at a dose of 75 mg/m2 after premedication with an anti-emetic such as ondansetron po or IV (up to a maximum dose of 16 mg ondansetron or equivalent). This phase will determine whether infusion of TAA-specific T cells (at dose level 2 - 1x10\^7) targeting multiple tumor antigens in combination with azacytidine is safe, and whether CTL infusions (with or without azacytidine) increase the spectrum of epitopes/antigens targeted by endogenous T cells (epitope spreading).

Group II: Pediatric multiTAA T cells Stage Experimental Treatment 1 Intervention

This phase will give patients \< 18 years old two infusions (on Day 0 and Day 14) of multi-TAA specific T cells at a fixed dose of 1x10\^7 cells/m2. This phase will test the safety and efficacy of multiTAA-specific T cells in pediatric patients with active HL/NHL.

Group III: Dose-Escalation Study Stage Experimental Treatment 1 Intervention

In the dose escalation stage, three dose levels will be studied. Patients in the dose escalation portion of the study will be entered and stratified separately to the following two groups: Group A: Patients receiving CTLs as therapy for Hodgkin's or non-Hodgkin's lymphoma. Group B: Patients receiving CTLs as adjunctive therapy following autologous or syngeneic transplant.

Group IV: Antigen-Escalation Stage Experimental Treatment 1 Intervention

The first stage will be an "antigen-escalation" stage using a fixed total dose of cells (5 x 10\^6 cells/m\^2 x 2) to evaluate the safety of the T cells primed against PRAME pepmix, and then SSX pepmix, and then MAGE A4 pepmix, and then NY-ESO pepmix, and then SURVIVIN pepmix.

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

Chimeric antigen receptor (CAR) T-cell therapies have shown promising results in treating patients with relapsed or refractory B-cell non-Hodgkin lymphoma, offering complete and lasting clinical responses where traditional therapies have failed.

Four CD19-directed CAR T-cell therapies have been approved by the FDA for specific types of relapsed or refractory lymphomas, indicating a significant advancement in treatment options for these challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relapsed/Refractory Non-Hodgkin Lymphoma: Engineering T-Cells to Express Chimeric Antigen Receptors (CARs), a Salvage? Kanwal, B.[2021]

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]

A new method has been developed to generate cytotoxic T lymphocytes (CTLs) that can target a variety of nonviral tumor-associated antigens in Hodgkin and non-Hodgkin lymphoma, potentially expanding treatment options for EBV-negative tumors.

This approach successfully produced CTLs from all nine healthy donors and five out of eight lymphoma patients, demonstrating its effectiveness across different human leukocyte antigen (HLA) types and suggesting a promising avenue for immunotherapy in a broader range of lymphoma cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytotoxic T lymphocytes simultaneously targeting multiple tumor-associated antigens to treat EBV negative lymphoma. Gerdemann, U., Katari, U., Christin, AS., et al.[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]

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