PD-1 Inhibition in Advanced Myeloproliferative Neoplasms
Condition: Chronic Phase Myelofibrosis; Primary Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis; Polycythemia Vera
MeSH terms: Neoplasms; Polycythemia Vera; Primary Myelofibrosis; Myeloproliferative Disorders; Polycythemia; Thrombocytosis; Thrombocythemia, Essential
Intervention: Pembrolizumab
Intervention description: 200 mg of Pembolizumab administered via intravenous infusion over 30 mins given every 3 weeks
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Myelofibrosis; Acute Leukemia

Summary:

      The purpose of this study is to test the effectiveness of a drug called pembrolizumab in
      patients with Myeloproliferative Neoplasm (MPN); chronic phase (MF-CP), accelerated phase
      (MPN-AP), or blast phase (MF-BP). Myelofibrosis neoplasm (MPN) is a group of diseases of the
      bone marrow in which excessive cells are produced.

      Pembrolizumab also known as Keytruda is a drug that has recently been approved in the United
      Stated by the Food and Drug Administration (FDA) for the treatment of patients with
      unresectable or metastatic melanoma and disease progression. Pembrolizumab is experimental in
      the treatment of MPN. The researchers want to find out what effects, good and /or bad it has
      on participants and the disease.

      Participants qualify to take part in this research study if have been diagnosed with a MPN
      blood disorder called myelofibrosis (MF). Accelerated (10-19% blasts in the blood or bone
      marrow) and blast phase (>20% blasts in the blood or bone marrow) MPN has been a difficult
      disease to treat. The term "blasts" refers to immature cells found in the bone marrow. They
      are not fully developed, and therefore, do not yet carry out any particular function within
      the body.

      Funds for conducting this research are provided by Merck and Company, the manufacturer of the
      study drug pembrolizumab.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Be willing and able to provide written informed consent/assent for the trial.

          -  Be ≥ 18 years of age on day of signing consent.

          -  Must have a diagnosis of chronic phase (CP) (defined as peripheral blood and bone
             marrow <10% blasts) primary myelofibrosis (PMF) or post essential thrombocythemia
             (post-ET) or polycythemia vera (post-PV) myelofibrosis by World Health Organization
             (WHO) criteria OR a diagnosis of a myeloproliferative neoplasm in accelerated/blast
             phase (MPN-AP/BP) defined as either a peripheral blood or bone marrow with =10% blasts
             .

          -  If the diagnosis is MF-CP, must have Dynamic International Prognostic Scoring System
             (DIPSS) intermediate-2/high risk disease and either be intolerant/resistant to
             ruxolitinib as determined by the treating investigator or ineligible for ruxolitinib
             therapy as determined by the treating investigator .

          -  If the diagnosis is MPN-AP/BP, must have progressive/resistant disease after treatment
             with a DNMT1 inhibitor therapy (azacytidine, decitabine) as determined by the treating
             investigator .

          -  Either not eligible or unwilling to proceed with hematopoietic stem cell
             transplantation (HSCT)

          -  Have a performance status of 0 or 1 on the ECOG Performance Scale.

          -  Demonstrate adequate organ function as defined in Table 1, all screening labs should
             be performed within 10 days of treatment initiation.

          -  Female subject 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 subjects of childbearing potential should be willing to use 2 methods of birth
             control or be surgically sterile, or abstain from heterosexual activity for the course
             of the study through 120 days after the last dose of study medication (Reference
             Section 5.7.2). Subjects of childbearing potential are those who have not been
             surgically sterilized or have not been free from menses for > 1 year.

          -  Male subjects should agree to use an adequate method of contraception starting with
             the first dose of study therapy through 120 days after the last dose of study therapy.

        Exclusion Criteria:

          -  Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy or used an investigational
             device within 4 weeks of the first dose of treatment.

          -  Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or
             child) who is investigational site or sponsor staff directly involved with this trial,
             unless prospective IRB approval (by chair or designee) is given allowing exception to
             this criterion for a specific subject.

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment.

          -  Has a known history of active TB (Bacillus Tuberculosis)

          -  Hypersensitivity to pembrolizumab or any of its excipients.

          -  Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
             Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events
             due to agents administered more than 4 weeks earlier.

          -  Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
             within 2 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at
             baseline) from adverse events due to a previously administered agent.

               1. Note: Subjects with = Grade 2 neuropathy are an exception to this criterion and
                  may qualify for the study.

               2. Note: If subject received major surgery, they must have recovered adequately from
                  the toxicity and/or complications from the intervention prior to starting
                  therapy.

          -  Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer.

          -  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 (eg., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

          -  Has known history of, or any evidence of active, non-infectious pneumonitis.

          -  Has an active infection requiring systemic therapy.

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, 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 trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment.

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
             "Anti-CD137 or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody
             (including ipilimumab or any other antibody or drug specifically targeting T-cell
             co-stimulation or checkpoint pathways)

          -  Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

          -  Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

          -  Has received a live vaccine within 30 days of planned start of study therapy. Note:
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
             attenuated vaccines, and are not allowed.