Myeloproliferative NeoplasmsPhase 2NCT01668173
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 2 study testing AUY922 in people with Myeloproliferative Neoplasms, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myeloproliferative Neoplasms
- What is being tested?
- AUY922
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2012to May 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
- 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.
Who cannot join
- 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).
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
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
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
- Being tested
- AUY922
- Keywords
- HSP90 Inhibitor, AUY922, 12-076
- Medical subject headings
- Myeloproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AUY922Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: AUY922 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2012 (estimated)
- Study startAug 2012
- Primary completionMay 2015
- Study completionMay 2015
Why it stopped: patient safety
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Myeloproliferative NeoplasmsStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Raajit Rampal, MD, PhD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01668173
- Sponsor's protocol ID
- 12-076
- Status last verified
- Apr 2016
- First submitted
- 13 Aug 2012
- Last updated
- 23 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01668173
- Acronym / sponsor ID
- 12-076
- Conditions
- Myeloproliferative Neoplasms
- Keywords
- HSP90 Inhibitor, AUY922, 12-076
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: patient safety
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Aug 2012
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 17 Aug 2012 (estimated)
- Results
- Posted 23 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AUY922 | Experimental | Drug: AUY922This 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AUY922AUY922 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. | Drug | AUY922 |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raajit Rampal, MD, PhD principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AUY922 in people with Myeloproliferative Neoplasms, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Objective Response (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2016.