Pembrolizumab in Treating Patients With Relapsed or Refractory Stage IB-IVB Mycosis Fungoides or Sezary Syndrome
Condition: Recurrent Mycosis Fungoides and Sezary Syndrome; Refractory Mycosis Fungoides and Sezary Syndrome; Stage IB Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIA Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIB Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIIA Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIIB Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IVA Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IVB Mycosis Fungoides and Sezary Syndrome AJCC v7
MeSH terms: Mycoses; Mycosis Fungoides; Sezary Syndrome; Syndrome
Intervention: Laboratory Biomarker Analysis; Pembrolizumab
Intervention description: Correlative studies; Given IV
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well pembrolizumab works in treating patients with stage
      IB-IVB mycosis fungoides or Sezary syndrome that has returned after a period of improvement
      or has not responded to at least one type of treatment. Monoclonal antibodies, such as
      pembrolizumab, may block cancer growth in different ways by targeting certain cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  This trial will include subjects with stage IB-IVB MF/SS (maximal stage since
             diagnosis will determine eligibility), and who have relapsed, are refractory, or
             progressed after at least one standard systemic therapy; current disease stage at time
             of entry will also be documented but will not be used for eligibility

          -  Subjects must have the following minimum wash-out and adverse event (AE) recovery
             period from previous treatments without treatment between documentation of
             relapse/progression and enrollment of specifically:

               -  >= 2 weeks for local radiation therapy

               -  >= 4 weeks for systemic cytotoxic anticancer agents, anticancer investigational
                  agents that are not defined as immunotherapy, or for tumor-targeting monoclonal
                  antibodies (mAbs) with the exception of alemtuzumab for which the washout is at
                  least 8 weeks

               -  >= 15 weeks for anti-cluster of differentiation (CD)137 or anti-cytotoxic
                  T-lymphocyte-associated protein 4 (CTLA-4) (including ipilimumab or any other
                  antibody or drug specifically targeting T-cell co-stimulation or checkpoint
                  pathways)

               -  >= 2 weeks from resolution (i.e., =< grade 1 or at baseline) from AEs due to
                  procedures performed or therapeutic agents administered

               -  >= 2 weeks for retinoids, interferons, vorinostat, romidepsin, denileukin
                  diftitox, and therapeutic doses of oral corticosteroids (physiologic replacement
                  doses of oral corticosteroids are allowed, topical corticosteroids are allowed)

               -  >= 2 weeks for phototherapy

               -  >= 1 week for topical therapy (including retinoid, nitrogen mustard, or
                  imiquimod)

          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             performance scale

          -  Life expectancy of at least 6 months

          -  Performed within 10 days of treatment initiation: Leukocytes >= 2,000/mcL

          -  Performed within 10 days of treatment initiation: Absolute neutrophil count >=
             1,500/mcL

          -  Performed within 10 days of treatment initiation: Platelets >= 100,000/mcL

          -  Performed within 10 days of treatment initiation: Hemoglobin >= 9 g/dL OR >= 5.6
             mmol/L

          -  Performed within 10 days of treatment initiation: Serum total bilirubin =< 1.5 x upper
             limit of normal (ULN) OR direct bilirubin =< ULN for subjects with total bilirubin
             levels > 1.5 ULN

          -  Performed within 10 days of treatment initiation: Aspartate aminotransferase (AST)
             (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)
             (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for patients
             with liver metastases

          -  Performed within 10 days of treatment initiation: Serum creatinine =< 1.5 x ULN OR
             measured or calculated creatinine clearance >= 60 mL/min for subject with creatinine
             clearance (CrCl) levels > 1.5 x institutional ULN (glomerular filtration rate [GFR]
             can also be used in place of creatinine or CrCl)

          -  Performed within 10 days of treatment initiation: International normalized ratio (INR)
             or prothrombin time (PT) =< 1.5 x ULN unless subject is receiving anticoagulant
             therapy in which case the INR or PT must be within the therapeutic range of intended
             use for the anticoagulant

          -  Performed within 10 days of treatment initiation: Activated partial thromboplastin
             time (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy in which
             case the aPTT must be within the therapeutic range of intended use for the
             anticoagulant

          -  Performed within 10 days of treatment initiation: Thyroid stimulating hormone (TSH)
             within institutional limits (ie: normal); if TSH is greater or less than institutional
             limits patients may participate if their thyroxine (T4) is within normal limits (WNL);
             patients may be on a stable dose of replacement thyroid medication; dose adjustments
             are allowed if needed

          -  Patients must provide tissue from a punch biopsy of the skin at baseline, at the time
             of a clinical event (at the time of response, progression or appearance of a new
             lesion) and at the end of treatment; additional punch biopsies every 3 cycles are
             optional; an archival tissue sample is optional

          -  Have measurable disease based on modified severity-weighted assessment tool (mSWAT);
             tumor lesions situated in a previously irradiated area are considered measurable if
             progression has been demonstrated in such lesions

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) from the time of the
             pre-study visit, through the course of the study and for 120 days after the last dose
             of study medication

               -  Female patients of childbearing potential should have a negative urine or serum
                  pregnancy within 72 hours prior to receiving the first dose of study medication;
                  if the urine test is positive or cannot be confirmed as negative, a serum
                  pregnancy test will be required

               -  Female patients of childbearing potential should be willing to use 2 methods of
                  birth control or be surgically sterile, or abstain from heterosexual activity
                  from the time of the pre-study visit, through the course of the study and for 120
                  days after the last dose of study medication; patients of childbearing potential
                  are those who have not been surgically sterilized or have not been free from
                  menses for > 1 year

               -  Should a woman become pregnant or suspect she is pregnant while she is
                  participating in this study, she should inform her treating physician
                  immediately; men treated or enrolled on this protocol must also agree to use
                  adequate contraception prior to the study, for the duration of study
                  participation, and 4 months after completion of MK-3475 administration

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Patients who have had chemotherapy or targeted small molecule therapy within 4 weeks
             (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who
             have not recovered from adverse events due to agents administered more than 4 weeks
             earlier

               -  Note: patients with =< grade 2 neuropathy are an exception to this criterion and
                  may qualify for the study

               -  Note: if patients received major surgery, they must have recovered adequately
                  from the toxicity and/or complications from the intervention prior to starting
                  therapy

          -  Patients who are currently participating in or have participated in a study of an
             investigational agent or using an investigational device within 4 weeks of the first
             dose of treatment

          -  Has a diagnosis of immunodeficiency or is receiving therapeutic systemic steroid
             therapy or any other form of immunosuppressive therapy within 7 days prior to the
             first dose of trial treatment

          -  Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not
             recovered (i.e., =< grade 1 or at baseline) from AEs due to agents administered more
             than 4 weeks earlier

          -  Has a known additional malignancy that is progressing or requires active treatment;
             exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
             skin, or in situ cervical cancer that has undergone potentially curative therapy

          -  Patients with known brain metastases should be excluded from this clinical trial

               -  Patients with carcinomatous meningitis should also be excluded

               -  Patients with previously treated brain metastases may participate provided they
                  are stable (without evidence of progression by imaging for at least 4 weeks prior
                  to the first dose of trial treatment and any neurologic symptoms have returned to
                  baseline), have no evidence of new or enlarging brain metastases, and are not
                  using steroids for at least 7 days prior to trial treatment

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to MK-3475

          -  Has an active autoimmune disease requiring systemic treatment within the past 3 months
             or a documented history of clinically severe autoimmune disease, or a syndrome that
             requires systemic steroids or immunosuppressive agents; patients with vitiligo or
             resolved childhood asthma/atopy would be an exception to this rule; patients that
             require intermittent use of bronchodilators or local steroid injections would not be
             excluded from the study; the use of physiologic doses of corticosteroids may be
             approved after consultation with the protocol principal investigator (PI) and Cancer
             Immunotherapy Trials Network (CITN); patients with hypothyroidism stable on hormone
             replacement or Sjogren's syndrome will not be excluded from the study

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the patient's
             participation for the full duration of the trial, or is not in the best interest of
             the patient 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

          -  Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand
             (L)1, anti-PD-L2

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, interstitial lung disease or active, non-infectious pneumonitis,
             symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or
             psychiatric illness/social situations that would limit compliance with study
             requirements

          -  History of other pulmonary disease such as emphysema or chronic obstructive pulmonary
             disease, (forced expiratory volume in one second [FEV1] < 60% of predicted for height
             and age); pulmonary function tests (PFTs) are required in patients with prolonged
             smoking history or symptoms of respiratory dysfunction

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-study visit through 120 days
             after the last dose of trial treatment; breastfeeding should be discontinued if the
             mother is treated with MK-3475

               -  Men and non-pregnant, non-breast-feeding women may be enrolled if they are
                  willing to use 2 methods of birth control or are considered highly unlikely to
                  conceive; highly unlikely to conceive is defined as 1) surgically sterilized, or
                  2) postmenopausal (a woman who is >= 45 years of age and has not had menses for
                  greater than 1 year will be considered postmenopausal), or 3) not heterosexually
                  active for the duration of the study; the two birth control methods can be
                  barrier method or a barrier method plus a hormonal method to prevent pregnancy;
                  patients should start using birth control from the time of the pre-study visit,
                  through the course of the study and for 120 days after the last dose of study
                  medication; the following are considered adequate barrier methods of
                  contraception: diaphragm, condom (by the partner), copper intrauterine device,
                  sponge, or spermicide; appropriate hormonal contraceptives will include any
                  registered and marketed contraceptive agent that contains an estrogen and/or a
                  progestational agent (including oral, subcutaneous, intrauterine, or
                  intramuscular agents)

               -  Patients should be informed that taking the study medication may involve unknown
                  risks to the fetus (unborn baby) if pregnancy were to occur during the study; in
                  order to participate in the study they must adhere to the contraception
                  requirement (described above) for the duration of the study and during the
                  follow-up period; if there is any question that a patient will not reliably
                  comply with the requirements for contraception, that patient should not be
                  entered into the study

               -  If a patient inadvertently becomes pregnant while on treatment with MK-3475, the
                  patient will immediately be removed from the study; the site will contact the
                  patient at least monthly and document the patient's status until the pregnancy
                  has been completed or terminated; the outcome of the pregnancy will be reported
                  without delay and within 24 hours if the outcome is a serious adverse experience
                  (e.g., death, abortion, congenital anomaly, or other disabling or
                  life-threatening complication to the mother or newborn); the study investigator
                  will make every effort to obtain permission to follow the outcome of the
                  pregnancy and report the condition of the fetus or newborn; if a male patient
                  impregnates his female partner the study personnel at the site must be informed
                  immediately and the pregnancy reported and followed

          -  Patients who are human immunodeficiency virus (HIV) positive may participate IF they
             meet the following eligibility requirements:

               -  They must be stable on their anti-retroviral regimen, and they must be healthy
                  from an HIV perspective

               -  They must have a CD4 count of greater than 250 cells/mcL

               -  They must not be receiving prophylactic therapy for an opportunistic infection

          -  Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or
             hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is
             detected)

          -  Has received a live vaccine within 30 days prior to the first dose of trial treatment

          -  Has a known human T-lymphotropic virus type 1 (HTLV) infection

          -  Patient has a history of (non-infectious) pneumonitis that required steroids or
             current pneumonitis