MABEL CTLs for EBV-Positive Lymphoma

(MABEL Trial)

Recruiting at1 trial location

Overseen by Rayne H. Rouce

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Baylor College of Medicine

No Placebo Group

Trial Summary

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

Treatment Details

Interventions

• Cyclophosphamide (Alkylating agents)
• Fludarabine (Anti-metabolites)
• MABEL CTLs (Virus Therapy)

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+

Paul Klotman

Baylor College of Medicine

Chief Executive Officer since 2010

MD, PhD

James Versalovic

Baylor College of Medicine

Chief Medical Officer since 2020

MD from Baylor College of Medicine

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Dr. John P. Cooke

The Methodist Hospital Research Institute

Chief Medical Officer since 2013

MD, PhD

Dr. Jenny Chang

The Methodist Hospital Research Institute

Chief Executive Officer

MBBChir from University of Cambridge, MHCM from Johns Hopkins University

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

Dr. Helen E. Heslop

Center for Cell and Gene Therapy, Baylor College of Medicine

Chief Executive Officer since 2017

M.D. from University of Otago, New Zealand

Dr. Chrystal U. Louis

Center for Cell and Gene Therapy, Baylor College of Medicine

Chief Medical Officer since 2024

M.D. from Tulane University School of Medicine