MABEL CTLs for EBV-Positive Lymphoma

(MABEL Trial)

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

38 Participants Needed

Trial Summary

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 MABEL CTLs treatment safe for humans?

Research shows that MABEL CTLs treatment is generally safe for humans, with minimal side effects like localized swelling and fever. Studies on similar treatments for EBV-related conditions have reported no severe adverse effects, indicating a high level of safety. ^{1 2 3 4 5}

How does the MABEL CTLs treatment differ from other treatments for EBV-positive lymphoma?

MABEL CTLs treatment is unique because it uses specially trained immune cells called cytotoxic T lymphocytes (CTLs) to target and destroy cancer cells associated with the Epstein-Barr virus (EBV). This approach is different from traditional treatments as it focuses on boosting the body's immune response specifically against EBV-related proteins found in the cancer cells, potentially offering a more targeted and effective therapy. ^{6 7 8 9 10}

What is the purpose of this trial?

The subject has a type of cancer or lymph gland disease associated with a virus called Epstein Barr Virus (EBV), which has come back, is at risk of coming back, or has not gone away after standard treatments. This research study uses special immune system cells called LMP, BARF-1 and EBNA1- specific cytotoxic T lymphocytes (MABEL CTLs). Some patients with Lymphoma (such as Hodgkin (HD) or non-Hodgkin Lymphoma (NHL)), T/NK-lymphoproliferative disease, or CAEBV, or solid tumors such as nasopharyngeal carcinoma (NPC), smooth muscle tumors, and leiomyosarcomas show signs of a virus called EBV before or at the time of their diagnosis. EBV causes mononucleosis or glandular fever ("mono" or the "kissing disease"). EBV is found in the cancer cells of up to half the patients with HD and NHL, suggesting that it may play a role in causing Lymphoma. 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. EBV is also found in the majority of NPC and smooth muscle tumors, and some leiomyosarcomas. We want to see if special white blood cells (MABEL CTLs) that have been trained to kill EBV infected cells can survive in your blood and affect the tumor. In previous studies, EBV CTLs were generated from the blood of the patient, which was often difficult if the patient had recently received chemotherapy. Also, it took up to 1-2 months to make the cells, which is not practical when a patient needs more urgent treatment. To address these issues, the MABEL CTLs were made in the lab in a simpler, faster, and safer way. The MABEL CTLs will still see LMP proteins but also two other EBV proteins called EBNA-1 and BARF. To ensure these cells are available for use in patients in urgent clinical need, we have generated MABEL CTLs from the blood of healthy donors and created a bank of these cells, which are frozen until ready for use. We have previously successfully used frozen T cells from healthy donors to treat EBV lymphoma and virus infections and we now have improved our production method to make it faster. In this study, we want to find out if we can use banked MABEL CTLs to treat HD, NHL, T/NK-lymphoproliferative disease, CAEBV, NPC, smooth muscle tumors or leiomyosarcoma. We will search the bank to find a MABEL CTL line that is a partial match with the subject. MABEL CTLs are investigational and not approved by the Food and Drug Administration.

Research Team

Rayne H. Rouce

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

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

My cancer is related to the Epstein-Barr virus.

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 has returned or is not responding to treatment.

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

References

1. United States 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. [2023]

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

Phase I clinical trial of valacyclovir and standard of care cyclophosphamide in children with endemic Burkitt lymphoma in Malawi. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Adoptive cellular immunotherapy for EBV lymphoproliferative disease. [2020]

4. England 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. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Treatment options for post-transplant lymphoproliferative disorder and other Epstein-Barr virus-associated malignancies. [2019]

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

Epstein-Barr virus-specific cytotoxic T lymphocyte responses in the blood and tumor site of Hodgkin's disease patients: implications for a T-cell-based therapy. [2021]

7. Japan 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]. [2022]

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

Treatment of Epstein-Barr virus-associated malignancies with specific T cells. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Detection of EBER nuclear RNA in T-cell lymphomas involving the skin--an in situ hybridization study. [2006]

10. United States 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. [2021]