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ACTIVE NOT RECRUITING

NCT02287311

PHASE1

Most Closely Matched 3rd Party Rapidly Generated LMP, BARF1 And EBNA1 Specific CTL, EBV-Positive Lymphoma (MABEL)

Sponsor: Baylor College of Medicine

View on ClinicalTrials.gov

Summary

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. Investigators want to see if special white blood cells (MABEL CTLs) that have been trained to kill EBV infected cells can survive in patients 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, investigators have generated MABEL CTLs from the blood of healthy donors and created a bank of these cells, which are frozen until ready for use. Investigators 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, investigators want to find out if they can use banked MABEL CTLs to treat HD, NHL, T/NK-lymphoproliferative disease, CAEBV, NPC, smooth muscle tumors or leiomyosarcoma. Investigators 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.

Official title: ADMINISTRATION OF MOST CLOSELY MATCHED THIRD PARTY RAPIDLY GENERATED LMP, BARF1 and EBNA1 SPECIFIC CYTOTOXIC T-LYMPHOCYTES TO PATIENTS WITH EBV-POSITIVE LYMPHOMA AND OTHER EBV-POSITIVE MALIGNANCIES

Key Details

Gender

All

Age Range

Any - Any

Study Type

INTERVENTIONAL

Enrollment

Start Date

2015-02

Completion Date

2029-03

Last Updated

2026-03-23

Healthy Volunteers

Conditions

Hodgkin Disease Non-Hodgkin Lymphoma Severe Chronic Active Epstein Barr Virus T/NK-lymphoproliferative Disease Nasopharyngeal Carcinoma Smooth Muscle Tumor

Interventions

BIOLOGICAL

MABEL CTLs

Dose escalation: DL1:2x10\^7 cells/m2+2x10\^7 cells/m2 DL2:2x10\^7cells/m2+5x10\^7 cells/m2 DL3:5x10\^7 cells/m2+1x10\^8 cells/m2 \*Doses are based on total CD3+cells/m2 Patients with active disease that have apparent clinical benefit at the 8 wk post 1st infusion (6 wks after 2nd infusion) or subsequent evaluations may receive up to 6 additional doses of CTLs at intervals at least 6 wks apart, each of which will consist of the same cell number as their second injection or below the original dose if there is not enough product available for the original dose. Patients may receive lymphodepleting chemotherapy (Cy/Flu) before additional infusions. Patients cannot receive additional doses until the initial safety profile is completed at 6 wks following the second infusion.

DRUG

Cyclophosphamide

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. 3 daily doses of cyclophosphamide (Cy: 500 mg/m2/day) together with fludarabine (Flu: 30 mg/m2) to induce lymphopenia, finishing at least 24 hours before CTL infusion.

DRUG

Fludarabine

If the patient's level of circulating T cells is relatively high, s/he may require treatment with cyclophosphamide and fludarabine before s/he receives MABEL CTLs. 3 daily doses of cyclophosphamide (Cy: 500 mg/m2/day) together with fludarabine (Flu: 30 mg/m2) to induce lymphopenia, finishing at least 24 hours before CTL infusion.

Inclusion Criteria: SCREENING 1. Any patient regardless of age or sex, with diagnosis of either: * EBV positive Hodgkin's lymphoma * EBV Positive non-Hodgkin's Lymphoma (regardless of histologic subtype) * EBV (associated)-T/NK-lymphoproliferative disease * Severe Chronic Active EBV (CAEBV) -- CAEBV is defined as patients with high EBV viral load in plasma or PBMC (\>4000 genomes per ug PBMC DNA) and/or biopsy tissue positive for EBV * Other EBV positive malignancies (e.g. nasopharyngeal carcinoma, smooth muscle tumors, etc.) AND * in first or subsequent relapse (Group A) * with active disease persisting despite therapy (Group B) * with active disease if immunosuppressive chemotherapy is contraindicated e.g. patients who develop Hodgkin disease after solid organ transplantation or if the lymphoma is a second malignancy e.g. a Richter's transformation of CLL. (Group C) 2. EBV positive tumor 3. Weighs at least 12kg 4. Informed consent (and assent as applicable) obtained from patient/guardian. TREATMENT 1. Any patient regardless of age or sex, with diagnosis of either: * EBV positive Hodgkin's lymphoma * EBV Positive non-Hodgkin's Lymphoma (regardless of histologic subtype) * EBV (associated)-T/NK-lymphoproliferative disease * Severe Chronic Active EBV (CAEBV) -- CAEBV is defined as patients with high EBV viral load in plasma or PBMC (\>4000 genomes per ug PBMC DNA) and/or biopsy tissue positive for EBV * Other EBV positive malignancies (e.g. nasopharyngeal carcinoma, smooth muscle tumors, etc.) AND * in first or subsequent relapse (Group A) * with active disease persist despite therapy (Group B) * with active disease if immunosuppressive chemotherapy is contraindicated e.g. patients who develop Hodgkin disease after solid organ transplantation or if the lymphoma is a second malignancy e.g. a Richter's transformation of CLL. (Group C) 2. EBV positive tumor 3. Patients with life expectancy greater than or equal to 6 weeks 4. Patients with bilirubin less than or equal to 3x upper limit of normal 5. AST less than or equal to 5x upper limit of normal 6. Hemoglobin greater than or equal to 7.0 (may be a transfused value) 7. Patients with a creatinine less than or equal to 2x upper limit of normal for age 8. Pulse oximetry of \> 90% on room air 9. Patients should have been off other investigational therapy for 30 days prior to infusion. 10. Patients with a Karnofsky/Lansky score of more than or equal to 50. 11. Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom. 12. Informed consent (and assent as applicable) obtained from patient/guardian. Exclusion Criteria: TREATMENT 1. Pregnant or lactating 2. Severe intercurrent infection 3. Current use of systemic corticosteroids more than 0.5 mg/kg/day 4. Patients receiving ATG, Campath, or other immunosuppressive T cell monoclonal antibodies within 30 days.

Locations (2)

Houston Methodist Hospital

Houston, Texas, United States

Texas Children's Hospital