Nivolumab With Epstein Barr Virus Specific T Cells (EBVSTS), Relapsed/Refractory EBV Positive Lymphoma (PREVALE) (PREVALE)
NonHodgkin Lymphoma, Lymphoproliferative Disorders, EBV Related Lymphoma
About this trial
This is an interventional treatment trial for NonHodgkin Lymphoma focused on measuring Nivolumab, Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Lymphoproliferative Disorders, EBV-specific T Cells
Eligibility Criteria
Inclusion Criteria:
PROCUREMENT Inclusion
Any patient, regardless of age* or sex, with measurable EBV-positive Hodgkin's or non-Hodgkin's Lymphoma, (regardless of the histological subtype)^ or EBV (associated)- T/NK- or B cell lymphoproliferative disease
* The first 3 patients enrolled will be adults. Patients <18 years of age are eligible if those first 3 patients do not experience dose limiting toxicity considered to be primarily related to the EBVST or Nivolumab.
^ Patients with relapsed or refractory lymphoma who failed or are ineligible for an autologous hematopoietic cell transplantation are also eligible for this study.
- EBV positive tumor (can be pending)
- Weighs at least 12kg
- Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given a copy of informed consent.
- Life expectancy of greater than 6 weeks.
TREATMENT Inclusion
- Any patient, regardless of age* or sex, with measurable EBV-positive Hodgkin's or non-Hodgkin's Lymphoma, (regardless of the histological subtype)^ or EBV (associated)-T/NK- or B cell lymphoproliferative disease
* The first 3 patients enrolled will be adults. Patients <18 years of age are eligible if those first 3 patients do not experience dose limiting toxicity considered to be primarily related to the EBVST or Nivolumab.
^ Patients with relapsed or refractory lymphoma who failed or are ineligible for an autologous hematopoietic cell transplantation are also eligible for this study.
And
- Hodgkin's lymphoma patients in second relapse or first relapse and refractory to at least two lines of salvage chemotherapy including Brentuximab Vedotin or primary refractory disease after at least two lines therapy or
- Non- Hodgkin's lymphoma patients in first relapse and/or refractory to at least one salvage chemotherapy or with primary refractory disease after at least two lines of therapy or in second or subsequent relapse or
- T/NK- or B lymphoproliferative disease in first relapse and/or refractory to at least one salvage chemotherapy or with primary refractory disease after at least two lines of therapy or in second or subsequent relapse
- EBV positive tumor
- Patients with life expectancy >/= 6 weeks.
- Patients with bilirubin less than or equal to 3x upper limit of normal
- AST less than or equal to 5x upper limit of normal
- Hgb more than 8.0 (may be a transfused value).
- Patients with a creatinine less than or equal to 2x upper limit of normal for age
- Pulse oximetry of more than 90% on room air
- Patients should have been off other investigational therapy for 4 weeks prior to entry in this study.
- Patients with a Karnofsky/Lansky score of >/= 60
- Recovered from acute toxic effects of prior chemotherapy at least one week before entering the study.
- 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.
- Informed consent explained to, understood and signed by patient/guardian. Patient/guardian given a copy of informed consent.
Exclusion Criteria:
PROCUREMENT Exclusion
- Active infection with HIV, HTLV, HBV, HCV (can be pending at this time)
- History of solid organ transplant
TREATMENT Exclusion
- Pregnant or lactating due to unknown effects of this therapy on a fetus or lactation
- Severe active intercurrent infection.
- Current use of systemic corticosteroids >0.5 mg/kg/day
- Currently receiving any investigational agents or radiotherapy within 4 weeks prior to entering the study.
- Patients with central nervous system involvement.
- History of allergic reactions attributed to nivolumab or any other checkpoint inhibitors.
- Uncontrolled autoimmune disease needing systemic steroids or steroid sparing agents except for hypothyroidism or type I diabetes.
- History of solid organ transplant
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Lipase more than 70U/ml
Sites / Locations
- Houston Methodist Hospital
- Texas Children's Hospital
Arms of the Study
Arm 1
Experimental
EBVST Cells + Nivolumab
PD1 inhibitor - nivolumab 3 mg/kg (max dose: 240 mg) Q 2 weeks for total 4 doses and repeat a day prior to each EBVST infusion. EBVST- 1 x 10^8/m2 at days +1 and +15. PD1 inhibitor - nivolumab 3 mg/kg (max dose: 240 mg) Q 2 weeks for total 4 doses and repeat a day prior to each EBVST infusion. Can receive up to 3 additional infusions of EBVSTs with a single dose of nivolumab at 6-12 week intervals starting at least 6 weeks after the second infusion if stable disease or a partial response at Week 8 evaluation