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. 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):
Memorial Sloan Kettering Cancer Center

August 13, 2012
August 17, 2012
January 4, 2016
May 23, 2016
May 23, 2016
August 2012
May 2015   (Final data collection date for primary outcome measure)
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.
efficacy [ Time Frame: 6 months ]
The primary endpoint is overall response rate defined as the rate of complete response, partial response and clinical improvement by six months.
Complete list of historical versions of study NCT01668173 on Archive Site
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  • safety [ Time Frame: 1 year ]
    and tolerability of AUY922 in patients with myeloproliferative neoplasms. Adverse events will be assessed according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 4.02.
  • pharmacodynamics of AUY922 [ Time Frame: 1 year ]
    via measurement of Hsp90, downstream targets of JAK2 (P-STAT3, P-STAT5, P-MAPK), client proteins of Hsp90 (AKT, Raf-1, EGFR, and HER2) by Western blot and flow cytometry. These will be serially compared from the evaluation at baseline. Peripheral blood and bone marrow aspirate samples from pretreatment and post-treatment will be assessed for the above proteins to assess the on-target effect of the AUY922.
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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
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

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.

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Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Myeloproliferative Neoplasms
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.
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.
Intervention: Drug: AUY922
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
May 2015
May 2015   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States
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Memorial Sloan Kettering Cancer Center
Memorial Sloan Kettering Cancer Center
Principal Investigator: Raajit Rampal, MD, PhD Memorial Sloan Kettering Cancer Center
Memorial Sloan Kettering Cancer Center
April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP