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.
Inclusion Criteria:
In order to be eligible to participate in this study, an individual must meet all of the
following criteria:
1. Ability to sign and date the consent form.
2. Stated willingness to comply with all study procedures and be available for the
duration of the study.
3. Be a male or female aged > or = 18.
4. 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, gamma/delta T-cell lymphoma, subcutaneous panniculitis like T-cell lymphoma,
and Nodal T-cell lymphomas with T-follicular helper phenotype.
5. Available pathology material (fine needle aspirate is inadequate) for review at
University of Colorado
6. 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.
7. ECOG performance status 0 - 2.
8. Laboratory status as follows:
- ANC > 1000 cells/mm3, unless cytopenias due to lymphoma (i.e., bone marrow
involvement or splenomegaly)
- Platelet Count > 100,000 /μL, or > 50,000 /μL if bone marrow involvement or
splenomegaly
- Total bilirubin ≤1.5 x upper normal limit, or ≤ 3 x upper normal limit if
documented hepatic involvement with lymphoma, or ≤ 5 x upper normal limit if
history of Gilbert's Disease.
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper
normal limit (≤ 5 x upper normal limit if documented hepatic involvement with
lymphoma).
- Serum creatinine < 2.0 mg/dL or calculated creatinine clearance (CrCl) > 45
mL/min (Cockcroft-Gault, Appendix)
- PT or INR, and PTT ≤ 1.5 x upper limit of normal unless patient is receiving
anticoagulants. If patient is on warfarin therapy, levels should be within
therapeutic range.
9. Patients with measurable disease. Measurable disease is defined as having at least one
objective measurable disease parameter. A clearly defined, bi-dimensionally measurable
defect or mass measuring at least 1.5 cm in diameter on the CT portion of a PET/CT or
CT scan or MRI (if appropriate) will constitute measurable disease. Proof of lymphoma
in the liver is required by a confirmation biopsy unless there is measurable disease
by imaging. Skin lesions can be used as measurable disease provided bi-dimensional
measurements are possible. Patients with non-measurable but evaluable disease may be
eligible after discussion with the PI. Abnormal PET/CT scans will not constitute
evaluable disease, unless verified by the CT scan portion, CT scan, or other
appropriate imaging.
10. For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use of contraceptive methods that result in a failure
rate of < 1% per year during the treatment period and for at least 180 days after the
last study treatment. A woman is considered to be of childbearing potential if she is
post-menarchal, has not reached a postmenopausal state (≥ 12 continuous months of
amenorrhea with no identified cause other than menopause), and has not undergone
surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive
methods with a failure rate of < 1% per year include bilateral tubal ligation, male
sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing
intrauterine devices and copper intrauterine devices. The reliability of sexual
abstinence should be evaluated in relation to the duration of the clinical trial and
the preferred and usual lifestyle of the patient. Periodic abstinence (e.g. calendar,
ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable
methods of contraception.
11. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive measures and agreement to refrain from donating sperm, as defined below:
With female partners of childbearing potential or pregnant female partners, men must
remain abstinent or use a condom during the treatment period and for at least 180 days
after the last dose of study treatment. Men must refrain from donating sperm during
this same period. The reliability of sexual abstinence should be evaluated in relation
to the duration of the clinical trial and the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
postovulation methods) and withdrawal are not acceptable methods of contraception.
12. Patient must be able to adhere to the study visit schedule and other protocol
requirements.
Exclusion Criteria:
An individual who meets any of the following criteria will be excluded from participation
in this study:
1. 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.
2. Patients with a diagnosis of other PTCL histologies other than those specified in the
inclusion criteria.
3. Primary T-cell CNS lymphoma; however, secondary CNS disease is not an exclusion
criteria.
4. Pregnant or breastfeeding females.
5. Contraindication to any of the required concomitant drugs or supportive treatments.
6. 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.
7. Ejection fraction of <45% by either MUGA or ECHO.
8. 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.
9. 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.
10. History of non-infectious pneumonitis requiring immuno-suppressive therapy.
11. Active hepatitis B or C (with measurable virus or antigen in serum) or HIV. Patients
who are seropositive because of hepatitis B virus vaccine or have a history of
hepatitis B (with no measurable virus or antigen in serum) are eligible.
12. Prior PD-1 or PD-L1 antibody treatment.
13. Has received a live virus vaccine in 30 days preceding start of therapy.
