Pembrolizumab in Treating Patients with Untreated Nasal Type Extranodal NK/T-Cell Lymphoma
This phase II trial studies how well pembrolizumab works in treating patients with nasal type extranodal natural killer (NK)/T-cell lymphoma. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Inclusion Criteria
- Histologic diagnosis of extranodal NK/T, nasal type cell lymphoma at the enrolling institution
- Have a performance status of =< 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
- Have measurable disease by PET/computed tomography (CT)
- Serum creatinine =< 1.5 x upper limit of normal OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN
- Serum total bilirubin =< 1.5 x ULN OR =< 3 x ULN for subjects with liver metastases
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for subjects with liver metastases
- Ejection fraction >= 50%
- Hemoglobin-adjusted diffusing capacity for carbon monoxide >= 50%
- Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours prior to receiving the first dose of study medication * A woman of childbearing potential is a sexually mature female who has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months (i.e. has had menses at any time in the preceding 24 consecutive months)
- Women of childbearing potential must be willing to use an adequate method of contraception * Must agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 120 days after the last dose of study therapy, or agree to completely abstain from heterosexual intercourse
- Male subjects of childbearing potential must agree to use an adequate method of contraception * Male subjects, even if surgically sterilized (i.e. status post vasectomy) must agree to 1 of the following: ** Practice effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study therapy, or agree to completely abstain from heterosexual intercourse
Exclusion Criteria
- Received prior treatment for extranodal NK/T cell lymphoma
- Medical illness unrelated to lymphoma, which, in the opinion of the treating physician and/or institutional principal investigator, makes participation in this study inappropriate
- Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed
- Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
- Has an active infection requiring systemic therapy
- Has a known history of human immunodeficiency virus (HIV)
- Has active hepatitis B (defined as hepatitis B virus [HBV] deoxyribonucleic acid [DNA] is detected) or known active hepatitis C virus (defined as HCV ribonucleic acid [RNA] is detected) infection
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject‘s participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment
- Has had an allogeneic tissue/solid organ transplant
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03728972.
PRIMARY OBJECTIVE:
I. Assess the complete response rate of pembrolizumab in untreated extranodal NK/T-cell lymphoma (ENKTL).
SECONDARY OBJECTIVES:
I. Assess safety of pembrolizumab as front line therapy for ENKTL.
II. Assess the partial response rate and overall response rate of pembrolizumab in untreated ENKTL.
III. Assess response after 2 cycles of pembrolizumab according to the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) criteria.
IV. Determine 2-year progression free survival and overall survival for newly diagnosed ENKTL treated with pembrolizumab-based therapy.
V. Explore mechanism of action and markers of response and resistance through assessment of baseline and on-treatment biopsies.
VI. Evaluate plasma Epstein-Barr virus (EBV) polymerase chain reaction (PCR) as a marker of response to therapy and/or early predictor of relapse.
OUTLINE: Patients are assigned to 1 of 2 arms.
ARM I (STAGES I AND II): Patients receive pembrolizumab via intravenous piggyback (IVPB) over 30 minutes on day 1. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. After 2 cycles of pembrolizumab, patients with no evidence of disease progression receive 2 additional cycles of pembrolizumab. Patients with an "indeterminant response" may receive 2 additional cycles of pembrolizumab per physician discretion. Patients with progression of disease without evidence of clinical improvement receive SMILE chemotherapy consisting of methotrexate IVPB over 6 hours on day 1, leucovorin IVPB every 6 hours, ifosfamide IVPB over 1 hour on days 2, 3, and 4, etoposide IVPB over 1 hour on days 2, 3, and 4 and dexamethasone IVPB on days 2, 3, and 4 and undergo ISRT. Treatment with SMILE chemotherapy repeats every 21-28 days for 2 cycles in the absence of disease progression of unacceptable toxicity. Patients who progress to stage III or IV ENKTL will discontinue treatment per physician discretion. After 4 cycles of pembrolizumab, patients with complete response (CR) receive 6 additional cycles of pembrolizumab and undergo ISRT within 2-6 weeks. Patients with less than CR undergo biopsy. Patients with less than CR and persistent evidence of disease on biopsy receive 2 cycles of SMILE chemotherapy and ISRT.
ARM II (STAGES III AND IV): Patients receive pembrolizumab IVPB over 30 minutes on day 1. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients with no evidence of disease progression receive 2 additional cycles of pembrolizumab. Patients with an "indeterminant response" may also receive 2 additional cycles of pembrolizumab per physician discretion. Patients who achieve a partial metabolic response (PMR) after 4 cycles of pembrolizumab receive SMILE chemotherapy. Treatment with SMILE chemotherapy repeats every 21-28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab IVPB over 30 minutes on day 1. Cycles repeat every 21 days for 10 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 3 years then every 6 months for 2 years.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorAlison J. Moskowitz
- Primary ID18-393
- Secondary IDsNCI-2018-03425
- ClinicalTrials.gov IDNCT03728972