We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov Menu

HSP90 Inhibitor, AUY922, in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), Post-Essential Thrombocythemia Myelofibrosis (Post-ET MF), and Refractory PV/ET

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01668173
Recruitment Status : Terminated (patient safety)
First Posted : August 17, 2012
Results First Posted : May 23, 2016
Last Update Posted : May 23, 2016
Information provided by (Responsible Party):

Study Description
Brief Summary:

The purpose of this study is to test a new drug called AUY922. AUY922 is not FDA-approved. AUY922 is a new kind of drug that attacks a protein called HSP90. HSP90 is found in both normal and cancer cells, but the investigators think it is more important in cancer cells.

This study will see if AUY922 helps people with myelofibrosis, essential thrombocythemia and polycythemia vera. This study will also see if AUY922 is safe in people with myelofibrosis, essential thrombocythemia and polycythemia vera. It will find out what effects, good and/or bad, AUY922 has on the patient and the disease. The researchers hope that this study will help them to find better treatments for primary myelofibrosis, essential thrombocythemia and polycythemia vera.

Condition or disease Intervention/treatment Phase
Myeloproliferative Neoplasms Drug: AUY922 Phase 2

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of the HSP90 Inhibitor, AUY922, in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), Post-Essential Thrombocythemia Myelofibrosis (Post-ET MF), and Refractory PV/ET
Study Start Date : August 2012
Primary Completion Date : May 2015
Study Completion Date : May 2015

Arms and Interventions

Arm Intervention/treatment
Experimental: AUY922
This is an open-label phase II trial to assess the efficacy of the HSP90 inhibitor, AUY922, in patients with PMF, post-PV MF, post-ET MF, and with PV/ET who are refractory to hydroxyurea, phlebotomy or anagrelide.
Drug: AUY922
AUY922 will be administered as an intravenous infusion over 60 minutes, on a once weekly schedule. A cycle on study will be defined as 28 days. The dose to be studied are 70 mg/m2 and 55 mg/m2 if DLTs are identified in the first 3-6 patients. The same schedule of administration will be used for all patients in this trial.

Outcome Measures

Primary Outcome Measures :
  1. Overall Objective Response [ Time Frame: 6 months ]
    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Eligible patients must have myeloproliferative neoplasms, specifically, primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (post-PV MF), post essential thrombocythemia myelofibrosis (post-ET MF), and PV/ET that are refractory to hydroxyurea, phlebotomy and anagrelide or not a candidate for standard therapies.
  • ≥ 18 years of age
  • ECOG performance status of 0-2
  • Acceptable pre-study organ function during screening as defined as:


  • Absolute Neutrophil Count (ANC) ≥1.5x109/L
  • Hemoglobin (Hgb) ≥ 8 g/dl (may be supported with transfusion)
  • Platelets (plt) ≥50x10^9/L


  • Potassium within normal limits
  • Total calcium (corrected for serum albumin) and phosphorus within normal limits
  • Magnesium above LLN or correctable with supplements Liver and Kidney Functions
  • AST/SGOT and ALT/SGPT ≤ 1.5 x Upper Limit of Normal (ULN) if AP > 2.5 X ULN
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5
  • Serum bilirubin ≤ 1.5 x ULN (Unless attributable to Gilbert's disease)
  • Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 ml/min
  • Negative serum pregnancy test. The serum pregnancy test must be obtained prior to the first administration of AUY922 (≤ 72 hours prior to dosing) in all pre-menopausal women and women <2 years after the onset of menopause
  • Patients who previously received JAK2 inhibitors will be eligible as long as they have been off the drug for more than 4 weeks.
  • Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

  • Requiring ongoing therapy with either G- or GM-CSF, or long-acting versions of these molecules
  • Active medical condition such as infection or cancer that is actively requiring treatment.
  • Unresolved diarrhea ≥ CTCAE (v4.02) grade 1
  • Prior anti-neoplastic treatment with any HSP90 or HDAC inhibitor compound
  • Patients who have undergone any major surgery ≤ 2 weeks prior to starting study drug or have not recovered from the side effects of such therapy.
  • Patient must be ≥ 4 weeks since last chemotherapy or treatment with another systemic anticancer agent with the exception of hydroxyurea. Hydroxyurea must be discontinued at least 48 hours prior to the initiation of AUY922. Patients must have recovered (CTC ≤ 1) from acute toxicities of any previous therapy (with the exception of alopecia).
  • Active anticoagulation with warfarin.
  • Pregnant or lactating women
  • Fertile women of childbearing potential (WCBP) not using double-barrier methods of contraception (abstinence, oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly, or surgically sterile). Male patients whose partners are WCBP not using double-barrier methods of contraception.

Impaired cardiac function, including any one of the following:

  • History (or family history) of long QT syndrome
  • Mean QTc ≥ 450 msec on baseline ECG
  • History of clinically manifested ischemic heart disease (including myocardial infarction, stable or unstable angina pectoris, coronary arteriography or cardiac stress testing/imaging with findings consistent with infarction or clinically significant coronary occlusion) ≤ 6 months prior to study start
  • History of heart failure or left ventricular (LV) dysfunction (LVEF ≤ 45%) by MUGA or ECHO
  • Clinically significant ECG abnormalities including 1 or more of the following: left bundle branch block (LBBB), right bundle branch block (RBBB) with left anterior hemiblock (LAHB). ST segment elevation or depression > 1mm, or 2nd (Mobitz II), or 3rd degree AV block.

History or presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or Torsades de Pointes

  • Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
  • Clinically significant resting bradycardia (< 50 beats per minute)
  • Patients who are currently receiving treatment with any medication which has a relative risk of prolonging the QTcF interval or inducing Torsades de Pointes and cannot be switched or discontinued to an alternative drug prior to commencing AUY922.
  • Obligate use of a cardiac pacemaker
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01668173

United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Principal Investigator: Raajit Rampal, MD, PhD Memorial Sloan Kettering Cancer Center
More Information

Additional Information:
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01668173     History of Changes
Other Study ID Numbers: 12-076
First Posted: August 17, 2012    Key Record Dates
Results First Posted: May 23, 2016
Last Update Posted: May 23, 2016
Last Verified: April 2016

Keywords provided by Memorial Sloan Kettering Cancer Center:
HSP90 Inhibitor

Additional relevant MeSH terms:
Primary Myelofibrosis
Polycythemia Vera
Myeloproliferative Disorders
Thrombocythemia, Essential
Bone Marrow Diseases
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders