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

NCT01668173 | Terminated Phase 2 Results

• 1 other identifier: 12-076
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Myeloproliferative Neoplasms

Keywords

HSP90 Inhibitor; AUY922; 12-076

Outcome Measures

Primary Outcomes (1)

• Overall Objective Response

  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.

  6 months

Study Arms (1)

AUY922

EXPERIMENTAL

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

Interventions

AUY922 DRUG

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.

AUY922

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Novartis: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Myeloproliferative Disorders

Interventions

5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Dr. Raajit Rampal
• Organization: Memorial Sloan Kettering Cancer Center

RampalR@mskcc.org

212-639-2194

Study Officials

• Raajit Rampal, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2012
• First Posted: August 17, 2012
• Study Start: August 1, 2012
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: May 23, 2016
• Results First Posted: May 23, 2016

Record last verified: 2016-04

Locations

US (1)