Nivolumab With Standard of Care Chemotherapy for the First Line Treatment of Peripheral T Cell Lymphoma
Overview
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 18
- Locations
- 3
- Primary Endpoint
- Efficacy: Complete Response Rate
Overview
Brief Summary
This regimen aims to become the first line treatment for peripheral T cell lymphoma, using nivolumab with the standard of care chemotherapy.
Detailed Description
Patients in this study will receive nivolumab in combination with the standard of care dose-adjusted EPOCH (etoposide, prednisone, vincristine, doxorubicin, cyclophosphamide) for six 21 day cycles. Patients will then have an autologous stem cell transplant or continue to receive maintenance therapy with nivolumab.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- •Ability to sign and date the consent form.
- •Stated willingness to comply with all study procedures and be available for the duration of the study.
- •Be a male or female aged 18-
- •Histologically confirmed new diagnosis of Stage II, III or IV Peripheral T-cell Non-Hodgkin's lymphoma not otherwise specified (NOS), Anaplastic large cell lymphoma (ALK-negative) (ALK-positive if IPI 3, 4, or 5), Angioimmunoblastic T-cell lymphoma, Enteropathy associated T-cell lymphoma (MEITL and EATL), Hepatosplenic T-cell lymphoma, y/8 T-cell lymphoma, Subcutaneous panniculitis-like T-cell lymphoma, and Nodal T-cell lymphomas with T-follicular helper phenotype.
- •Available pathology material (fine needle aspirate is inadequate) for review at the University of Colorado.
- •No prior therapy with the exception of prior radiation therapy and/or 1 cycle of chemotherapy (may be any chemotherapy regimen or even prednisone alone) based on current diagnosis and clinical condition. If given cytotoxic chemotherapy (one cycle only, e.g. CHOP), this cycle of treatment will count toward the 6 cycles of treatment given in the study.
- •ECOG performance status 0 -
- •Laboratory status as follows:
- •ANC \> 1000 cells/mm3, unless cytopenias due to lymphoma (i.e., bone marrow involvement or splenomegaly)
Exclusion Criteria
- •An individual who meets any of the following criteria will be excluded from participation in this study:
- •An additional malignancy treated with palliative intent within the past 2 years. Malignancies in patients who have completed definitive treatment with curative intent \>1 year will be permitted after discussion with the PI. Adequately treated basal cell, squamous cell skin cancer, or thyroid cancer; carcinoma in situ of the cervix or breast; prostate cancer of Gleason Grade 6 or less with stable PSA levels are allowed.
- •Patients with a diagnosis of other PTCL histologies other than those specified in the inclusion criteria.
- •Primary T-cell CNS lymphoma; however, secondary CNS disease is not an exclusion criteria.
- •Pregnant or breastfeeding females.
- •Contraindication to any of the required concomitant drugs or supportive treatments.
- •Any other clinically significant medical disease or condition laboratory abnormality or psychiatric illness that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent.
- •Ejection fraction of \<45% by either MUGA or ECHO.
- •Has immunodeficiency or is being treated with immuno-suppressive therapy (aside from medications used to treat lymphoma) within 7 days of first dose of study treatment. Inhaled or topical steroids are accepted. Prednisone used to treat adrenal insufficiency in the absence of auto-immune disease is also acceptable.
- •Auto-immune condition requiring immuno-suppressive disease modifying therapy within the prior 2 years. Replacement therapy, e.g. levothyroxine for thyroiditis or insulin for diabetes are acceptable.
Arms & Interventions
Nivolumab and EPOCH
Patients will all receive nivolumab in combination with standard dose adjusted EPOCH for a planned 6 cycles, unless treatment is stopped early for disease progression or toxicity. Patients that have already received up to 1 cycle of standard of care chemotherapy will receive 5 cycles of experimental nivolumab + DA-EPOCH (dose adjusted, continuous infusion etoposide, prednisone, vincristine, doxorubicin, and bolus dosing of cyclophosphamide) for a total of 6 cycles of chemotherapy.
Intervention: Nivolumab (Drug)
Nivolumab and EPOCH
Patients will all receive nivolumab in combination with standard dose adjusted EPOCH for a planned 6 cycles, unless treatment is stopped early for disease progression or toxicity. Patients that have already received up to 1 cycle of standard of care chemotherapy will receive 5 cycles of experimental nivolumab + DA-EPOCH (dose adjusted, continuous infusion etoposide, prednisone, vincristine, doxorubicin, and bolus dosing of cyclophosphamide) for a total of 6 cycles of chemotherapy.
Intervention: Etoposide (Drug)
Nivolumab and EPOCH
Patients will all receive nivolumab in combination with standard dose adjusted EPOCH for a planned 6 cycles, unless treatment is stopped early for disease progression or toxicity. Patients that have already received up to 1 cycle of standard of care chemotherapy will receive 5 cycles of experimental nivolumab + DA-EPOCH (dose adjusted, continuous infusion etoposide, prednisone, vincristine, doxorubicin, and bolus dosing of cyclophosphamide) for a total of 6 cycles of chemotherapy.
Intervention: Prednisolone (Drug)
Nivolumab and EPOCH
Patients will all receive nivolumab in combination with standard dose adjusted EPOCH for a planned 6 cycles, unless treatment is stopped early for disease progression or toxicity. Patients that have already received up to 1 cycle of standard of care chemotherapy will receive 5 cycles of experimental nivolumab + DA-EPOCH (dose adjusted, continuous infusion etoposide, prednisone, vincristine, doxorubicin, and bolus dosing of cyclophosphamide) for a total of 6 cycles of chemotherapy.
Intervention: Oncovin (Drug)
Nivolumab and EPOCH
Patients will all receive nivolumab in combination with standard dose adjusted EPOCH for a planned 6 cycles, unless treatment is stopped early for disease progression or toxicity. Patients that have already received up to 1 cycle of standard of care chemotherapy will receive 5 cycles of experimental nivolumab + DA-EPOCH (dose adjusted, continuous infusion etoposide, prednisone, vincristine, doxorubicin, and bolus dosing of cyclophosphamide) for a total of 6 cycles of chemotherapy.
Intervention: Cyclophosphamide (Drug)
Nivolumab and EPOCH
Patients will all receive nivolumab in combination with standard dose adjusted EPOCH for a planned 6 cycles, unless treatment is stopped early for disease progression or toxicity. Patients that have already received up to 1 cycle of standard of care chemotherapy will receive 5 cycles of experimental nivolumab + DA-EPOCH (dose adjusted, continuous infusion etoposide, prednisone, vincristine, doxorubicin, and bolus dosing of cyclophosphamide) for a total of 6 cycles of chemotherapy.
Intervention: Hydroxydaunorubicin (Drug)
Outcomes
Primary Outcomes
Efficacy: Complete Response Rate
Time Frame: up to 100 days post transplant
Efficacy will be measured according to 2017 RECIL criteria. Responses will be assessed by the investigator and will be based on PET/CT scan to be obtained after 6 cycles of induction chemotherapy.
Secondary Outcomes
- Number of Participants With Adverse Events(up to 100 days after last dose of nivolumab)
- Efficacy: Overall Response Rate(up to 100 days post transplant)
- Efficacy: Progression Free Survival Rate(up to 2 years after completion of treatment)
- Efficacy: Event Free Survival(up to 2 years after completion of treatment)
- Immune-related Predictors of Response(Within 6 months of treatment)