Open Label Study of Single Agent Oral RG7388 in Patients With Polycythemia Vera and Essential Thrombocythemia

Description

This research looks at two conditions, Essential Thrombocythemia (ET) and Polycythemia Vera (PV). ET causes people to produce too many blood cells called platelets and PV causes too many platelets and red blood cells to be made. Platelets are particles which circulate in the blood stream and normally prevent bleeding and bruising. Having too many platelets in the blood increases the risk of developing blood clots, which can result in life threatening events like heart attacks and strokes. When the number of red blood cells is increased in PV this will slow the speed of blood flow in the body and increase the risk of developing blood clots. The purpose of Part A of this study is to test the safety and tolerability of drug RG7388 patients and identify the recommended phase II dose in a single agent dose escalation study. The investigators want to find out what effects, good and/or bad it has on the disease. The purpose of Part B of this study is to test the safety and tolerability of the combination of RG7388 and Pegylated Interferon Alfa-2a or Pegasys in PV/ET patients from Part A who did not achieve at least a partial response by the end of three cycles of single agent RG7388. Essential Thrombocythemia (ET) and Polycythemia Vera (PV) have been difficult diseases to treat. RG7388 is a selective inhibitor of the p53-MDM2 binding that frees p53 from negative control and activates the p53 pathway in cancer cells, leading to cell cycle arrest and apoptosis in vitro and in vivo. It has been used to treat solid tumors and Acute Myelogenous Leukemia (AML) in clinical trials. Pegasys is a drug that is the standard of care for patients who have Chronic Hepatitis B (CHB). RG7388 is a drug that is not yet approved by the Federal Drug Administration (FDA) for the treatment of patients with essential thrombocythemia or polycythemia vera. Pegasys is a drug that is approved by the FDA for the treatment of CHB. The use of RG7388 alone and in combination with Pegasys is experimental.

Study Start Date

April 2015

Estimated Completion Date

April 2018

Interventions

  • Drug: RG7388
  • Drug: Pegasys

Specialties

  • Oncology: Anemia/Polycythemia
  • Physician Assistant: Hematology/Oncology

MeSH Terms

  • Pegasys
  • Polycythemia Vera

Study ID

Mount Sinai School of Medicine -- GCO 14-1919

Status

Unknown

Trial ID

NCT02407080

Study Type

Interventional

Trial Phase

Phase 1

Enrollment Quota

30

Sponsor

Mount Sinai School of Medicine

Inclusion Criteria

    (Patient should meet all the criteria)
  • JAK2V617F-positive PV or JAK2V617F-positive ET (confirmed by WHO diagnostic criteria)
  • High risk ET/PV [age >60
  • history of thrombosis] or low risk disease with symptoms [recurrent headaches, paresthesias, pruritus]
  • Previously treated with at least one other agent [hydroxyurea, interferon, anagrelide] and determined to be either intolerant/resistant -?18 years of age
  • Eastern Cooperative Oncology Group (ECOG) Performance status 0-2
  • Acceptable pre-study organ function during screening as defined as: Total bilirubin ? 1.5 times the upper limit of normal (ULN) unless due to Gilbert's disease or hemolysis, Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ? 2.5 times ULN, Serum creatinine ? 1.5 x ULN
  • Women of childbearing potential and males must agree to use adequate contraception (i.e., hormonal or barrier method of birth control
  • abstinence) prior to study entry and for the duration of study participation. Should a female subject become pregnant or suspect she is pregnant while participating in this study, she should inform the treating physician immediately
  • Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria

  • Meets the criteria for post ET/PV MF as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)
  • Blast phase disease (>20% blasts in the marrow or peripheral blood)
  • Acute thrombosis within 3 months of screening
  • Uncontrolled intercurrent illness including, but not limited to hepatitis, human immunodeficiency virus (HIV)
  • positive subjects receiving combination antiretroviral therapy, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, ventricular arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Gender

Both

Ages

18 Years and older

Accepts Healthy Volunteers

No

Study Locations and Contact Information (6)

Study Location Distance Name Phone Email
Icahn School of Medicine at Mount Sinai - New York, New York 46.8 miles John Mascarenhas MD 212-241-3417 john.mascarenhas@mssm.edu
Memorial SloanKettering Cancer Center - New York, New York 50.7 miles Raajit Rampal MD PhD 212-639-2194 rampalr@mskcc.org
University of Pennsylvania - Philadelphia, Pennsylvania 134.5 miles Elizabeth Hexner MD 215-662-4137 elizabeth.hexner@uphs.upenn.edu
Wake Forest University Baptist Medical Center - Winston-Salem, North Carolina 523.1 miles Dmitry Berenzon MD 336-716-5847 dberenzo@wfubmc.edu
University of Utah - Salt Lake City, Utah 2,001.2 miles Josef Prchal MD 801-581-4220 Josef.Prchal@hsc.utah.edu
Mayo Clinic - Scottsdale, Arizona 2,167.5 miles Ruben Mesa MD 480-301-8335 mesa.ruben@mayo.edu

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