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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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|
- efficacy [ Time Frame: 6 months ] [ Designated as safety issue: No ]The primary endpoint is overall response rate defined as the rate of complete response, partial response and clinical improvement by six months.
- safety [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]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 ] [ Designated as safety issue: No ]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.
|Study Start Date:||August 2012|
|Estimated Study Completion Date:||August 2015|
|Estimated Primary Completion Date:||August 2015 (Final data collection date for primary outcome measure)|
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01668173
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Raajit Rampal, MD, PhD||Memorial Sloan Kettering Cancer Center.|