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PD-1 Inhibition in Advanced Myeloproliferative Neoplasms

Descriptive Information
Brief Title † PD-1 Inhibition in Advanced Myeloproliferative Neoplasms
Official Title † PD-1 Inhibition in Advanced Myeloproliferative Neoplasms
Brief 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.
Detailed Description The researchers propose a Simon-two stage design for this study. The researchers will test pembrolizumab at the FDA approved dose (in head and neck cancer) of 200mg dose administered via intravenous infusion over 30 minutes given every 3 weeks. Nine patients will be enrolled in the first stage of the Simon-two stage design, and 15 in the second stage. A treatment cycle is 3 weeks and the core study period is 6 cycles. Response assessment by established consensus criteria will be used to assess response after 6 cycles in order to determine if the trial will progress to the second stage and for the purpose of determining the primary endpoint. In addition, allowed will be a maximum of ten patients with accelerated or blast phase disease (MPN-AP/BP) who are refractory or intolerant to conventional therapies such as decitabine, and in which hematopoietic stem cell transplant is not a therapeutic option (exploratory cohort), to enroll in the study as a separate exploratory cohort. These patients can be enrolled during stage 1 or 2 and will be analyzed separately from the primary cohort population. Exploratory biomarkers will be obtained from enrolled patients at baseline, cycle 3 and cycle 7 and at 1 year of therapy. Patients that obtain at least a clinical improvement after 6 cycles of therapy can continue receiving pembrolizumab until evidence of disease progression, unacceptable toxicity, and patient or physician decision for a maximum of 2 years.
Study Phase Phase 2
Study Type † Interventional
Study Design †
Primary Outcome Measure † European Leukemia Net -International Working Group (ELN-IWG) criteria
Secondary Outcome Measure † Acute Myeloid Leukemia Response Criteria
Condition † Chronic Phase Myelofibrosis Primary Myelofibrosis Post-essential Thrombocythemia Myelofibrosis Polycythemia Vera
Intervention † DrugPembrolizumab
Study Arms / Comparison Groups Pembolizumab
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Drug
Estimated Enrollment † 34
Start Date † April 1, 2017
Completion Date April 30, 2020
Primary Completion Date April 30, 2019
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 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.
Gender All
Ages 18 Years - N/A
Accepts Healthy Volunteers No
Contacts †† John Mascarenhas, MD, 212-241-3417, john.mascarenhas@mssm.edu
Location Countries † United States
Administrative Information
NCT ID † NCT03065400
Organization ID GCO 16-2350
Secondary IDs ††
Responsible Party Sponsor-Investigator
Study Sponsor † John Mascarenhas
Collaborators †† Massachusetts General Hospital
Investigators † Study Chair: John Mascarenhas, MD, Icahn School of Medicine at Mount Sinai
Information Provided By
Verification Date February 2017
First Received Date † February 22, 2017
Last Updated Date February 22, 2017
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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