MABEL CTLs for EBV-Positive Lymphoma

(MABEL Trial)

Not currently recruiting at 1 trial location

Overseen By Rayne H. Rouce

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: Corticosteroids, ATG, Campath

Disqualifiers: Pregnant, Severe infection, others

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

Compensation: Varies

Number of Visits: 1

Duration: 8-12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for certain cancers linked to the Epstein-Barr Virus (EBV) using specialized immune cells called MABEL CTLs (cytotoxic T lymphocytes). The researchers aim to determine if these cells, taken from healthy donors and stored for quick use, can effectively target and kill cancer cells infected by EBV. The study seeks participants with EBV-related cancers, such as Hodgkin's lymphoma, non-Hodgkin's lymphoma, and nasopharyngeal carcinoma, particularly if standard treatments have failed or are unsuitable. 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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not be on other investigational therapies for 30 days before the infusion, and you cannot be using certain immunosuppressive drugs like ATG or Campath within 30 days of the trial.

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

Research has shown that MABEL CTLs are generally safe for humans, with minor side effects like localized swelling and fever. Previous studies on similar treatments, such as EBV-specific T-cell infusions, indicate that this method is safe and can help treat EBV-related lymphomas. Although MABEL CTLs are still under study and not yet approved by the FDA, the safety results so far appear promising. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for EBV-positive lymphoma, which often involve chemotherapy or immunotherapy, MABEL CTLs offer a unique approach by using modified cytotoxic T lymphocytes. These T cells are engineered to specifically target and eliminate cancerous cells associated with the Epstein-Barr virus. Researchers are excited about MABEL CTLs because they have the potential to be more targeted, potentially leading to fewer side effects compared to conventional therapies. Additionally, this treatment might offer an option for patients who cannot tolerate aggressive chemotherapy.

What evidence suggests that MABEL CTLs might be an effective treatment for EBV-positive lymphoma?

Previous studies have shown that infusions of special immune cells called EBV-specific T-cells (EBVST) hold promise in treating lymphomas linked to the Epstein Barr Virus (EBV). One study involving patients with a type of T-cell lymphoma reported a 66.7% response rate with this therapy. In this trial, participants will receive MABEL CTLs, designed to find and destroy cancer cells infected by EBV. Researchers quickly and safely produce these cells using cells from healthy donors, enabling urgent treatment. This method has successfully treated EBV-related lymphoma and infections in the past. ^{1 2 3 4 6}

Who Is on the Research Team?

Rayne H. Rouce

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for individuals of any age or sex with certain EBV-positive cancers, such as Hodgkin's lymphoma, non-Hodgkin's lymphoma, and others. Participants must weigh at least 12kg, have a life expectancy of over 6 weeks, normal organ function tests, and be off other investigational therapies for 30 days. Pregnant or breastfeeding individuals and those on high-dose steroids or recent T cell antibodies are excluded.

Inclusion Criteria

Patients with EBV positive tumor, life expectancy greater than or equal to 6 weeks, bilirubin less than or equal to 3x upper limit of normal, AST less than or equal to 5x upper limit of normal, hemoglobin greater than or equal to 7.0, creatinine less than or equal to 2x upper limit of normal for age, pulse oximetry of > 90% on room air, off other investigational therapy for 30 days prior to infusion, Karnofsky/Lansky score of more than or equal to 50, sexually active patients willing to utilize effective birth control methods, informed consent obtained from patient/guardian

My cancer is related to the Epstein-Barr virus.

My tumor is EBV positive, I weigh more than 12kg, and consent has been given.

Exclusion Criteria

I have not received ATG, Campath, or similar immune-targeting drugs in the last 30 days.

I am taking more than 0.5 mg/kg/day of corticosteroids.

Pregnant or lactating

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive MABEL CTLs, with two doses given two weeks apart. Additional doses may be given up to 6 times.

8-12 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including imaging studies 8 weeks after the first CTL infusion and 1 to 3 months after the final dose.

5 years

Yearly follow-up (in-person or contact by research staff)

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Fludarabine
• MABEL CTLs

Trial Overview The study is testing MABEL CTLs—special immune cells designed to fight cancer by targeting the Epstein-Barr Virus (EBV) in various malignancies. These cells come from healthy donors and are matched to patients' profiles. The trial also uses Cyclophosphamide and Fludarabine to prepare the body for MABEL CTL infusion.

How Is the Trial Designed?

Group I: Group C: MABEL CTLs Experimental Treatment 3 Interventions

Patients with active disease if immunosuppressive chemotherapy is contraindicated. Three different dosing schedules will be evaluated. Two to four patients will be evaluated on each dosing schedule. Each patient will receive 2 injections, 14 days apart. If the patient's level of circulating T cells is relatively high, s/he may require treatment with cyclophosphamide (Cytoxan) and Fludarabine before s/he receives MABEL CTLs.

Group II: Group B: MABEL CTLs Experimental Treatment 3 Interventions

Patients with persistent active disease despite therapy. Three different dosing schedules will be evaluated. Two to four patients will be evaluated on each dosing schedule. Each patient will receive 2 injections, 14 days apart. If the patient's level of circulating T cells is relatively high, s/he may require treatment with cyclophosphamide (Cytoxan) and Fludarabine before s/he receives MABEL CTLs.

Group III: Group A: MABEL CTLs Experimental Treatment 3 Interventions

Patients with 1st or subsequent relapse. Three different dosing schedules will be evaluated. Two to four patients will be evaluated on each dosing schedule. Each patient will receive 2 injections, 14 days apart. If the patient's level of circulating T cells is relatively high, s/he may require treatment with cyclophosphamide (Cytoxan) and Fludarabine before s/he receives MABEL CTLs.

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+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

Published Research Related to This Trial

Adoptive transfer of autologous cytotoxic T lymphocytes (CTLs) targeting Epstein-Barr virus (EBV) is effective in preventing and treating post-transplant lymphoproliferative disease (PTLD) in solid organ transplant recipients, providing long-term immunity against recurrence.

The review discusses the potential of EBV-specific CTLs not only for PTLD but also for other EBV-related cancers, such as Hodgkin's disease and Burkitt's lymphoma, while highlighting the challenges in customizing therapies based on individual disease characteristics and EBV antigen expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment options for post-transplant lymphoproliferative disorder and other Epstein-Barr virus-associated malignancies. Davis, JE., Moss, DJ.[2019]

Antigen-specific cytotoxic T lymphocytes (CTLs) generated from induced pluripotent stem cells show rejuvenated function and strong antitumor effects against Epstein-Barr virus (EBV)-associated lymphomas, which are common in Asia and have a poor prognosis.

The study developed allogeneic EBV-specific CTLs for potential 'off-the-shelf' therapy, making it feasible for clinical use in treating these lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Induced pluripotent stem cell-derived rejuvenated cytotoxic T lymphocyte therapy for Epstein-Barr virus-associated lymphomas: application to clinical practice]. Ando, M.[2022]

In a study of 114 patients receiving EBV-specific cytotoxic T lymphocyte (CTL) infusions, the treatment showed minimal toxicity and effectively prevented EBV-related lymphoproliferative disease (LPD), with no cases in the 101 patients who received prophylaxis.

Among the 13 patients treated for existing LPD, 11 achieved sustained complete remissions, demonstrating the efficacy of CTLs in treating this condition, with functional CTLs persisting for up to 9 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Heslop, HE., Slobod, KS., Pule, MA., et al.[2023]

In a study involving 9 patients with refractory or recurrent angioimmunoblastic T-cell lymphoma (AITL), EBV-specific CTL therapy demonstrated a 66.7% response rate, with 55.6% achieving objective remission after treatment.

The therapy was found to be safe, with only mild side effects like fever and rash reported, and no cases of graft-versus-host disease, indicating a favorable safety profile for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of Epstein-Barr virus-specific antigen peptide-activated cytotoxic T-cells treatment for refractory or recurrent angioimmunoblastic T-cell lymphoma: A prospective clinical observational study. Bingjie, W., Lihong, W., Yongjin, S., et al.[2020]

EBV-specific cytotoxic T lymphocytes (CTLs) can be successfully generated from patients with Hodgkin's disease, showing potential as a treatment option for EBV-positive cases, with successful generation in 9 out of 13 patients studied.

Infused CTLs persisted in the body for over 13 weeks and maintained their ability to combat EBV, suggesting that this adoptive transfer approach could enhance the immune response in patients with relapsed Hodgkin's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes for the treatment of patients with EBV-positive relapsed Hodgkin's disease. Roskrow, MA., Suzuki, N., Gan, Yj., et al.[2021]

In a phase I safety study involving children aged 3-15 with EBV-associated Burkitt lymphoma, the combination of valacyclovir and cyclophosphamide was found to be safe, with no dose-limiting toxicities reported.

Patients treated with the combination showed a decrease in serum EBV viral loads, indicating a potential benefit that warrants further investigation in phase II efficacy trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical trial of valacyclovir and standard of care cyclophosphamide in children with endemic Burkitt lymphoma in Malawi. Olson, D., Gulley, ML., Tang, W., et al.[2021]

Citations

1. withpower.com withpower.com/trial/mabel-ctls-for-ebv-positive-lymphoma-9f946

MABEL CTLs for EBV-Positive Lymphoma (MABEL Trial) In a study involving 9 patients with refractory or recurrent angioimmunoblastic T-cell lymphoma (AITL), EBV-specific CTL therapy demonstrated a 66.7% response ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02287311

Study Details | NCT02287311 | Most Closely Matched 3rd ... The cancer cells (in lymphoma) and some immune system cells (in CAEBV) infected by EBV are able to hide from the body's immune system and escape destruction.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39908567/

Differential antibody response to EBV proteome ... - PubMed We comprehensively characterized antibody responses to the complete EBV proteome using a custom protein microarray in 56 patients with EBV-associated lymphoma ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S247395292500076X

Differential antibody response to EBV proteome following ... EBV-specific T-cell (EBVST) infusions have shown promise in safety and clinical effectiveness in treating EBV-associated lymphomas; however, ...

5. clinconnect.io clinconnect.io/trials/NCT02287311

Most Closely Matched 3rd Party Rapidly Generated LMP The researchers are using special immune cells, called MABEL CTLs, which are designed to target and kill the cancer cells infected by EBV. These cells are ...

6. ashpublications.org ashpublications.org/blood/article/142/17/1426/497352/How-I-treat-posttransplant-lymphoproliferative

How I treat posttransplant lymphoproliferative disorder | Blood Antiviral therapy for EBV-related lymphomas has not been effective. Drugs such as acyclovir exert antiviral effects by inhibiting lytic viral ...