Pembrolizumab in Treating Patients With Relapsed or Refractory Stage IB-IVB Mycosis Fungoides or Sezary Syndrome

Not Recruiting

Trial ID: NCT02243579


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.

Official Title

A Phase 2 Study of MK-3475 for the Treatment of Relapsed/Refractory Mycosis Fungoides/Sezary Syndrome

Stanford Investigator(s)

Youn H Kim, MD
Youn H Kim, MD

The Joanne and Peter Haas, Jr., Professor for Cutaneous Lymphoma Research and Professor, by courtesy, of Medicine (Oncology)

Michael Khodadoust
Michael Khodadoust

Assistant Professor of Medicine (Oncology) and of Dermatology


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

      - >= 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

   - 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 >=

   - 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

   - 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

   - 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

      - 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

   - 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

   - 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

   - 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


other: Laboratory Biomarker Analysis

biological: Pembrolizumab

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305

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