A Study of the HSP90 Inhibitor AUY922

NCT01485536 | Terminated Phase 2 Results

• 2 other identifiers: 2011-0467NCI-2012-00070
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if AUY922 can help to control refractory or recurrent lymphoma. The safety of AUY922 will also be studied. AUY922 is designed to block tumor growth by blocking a protein.

Conditions

Lymphoma

Keywords

Lymphoma; Relapsed/refractory lymphoma; AUY922

Outcome Measures

Primary Outcomes (2)

• Objective Response in Participants With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL) and Peripheral T-cell Lymphoma (PTCL)

  Objective Response defined as Complete (CR) and Partial (PR) Response. Computed tomography (CT) and Positron emission tomography (PET) scans done after every 2 cycles to assess efficacy using Cheson Criteria (2007) which lists CR as disappearance of all evidence of disease, and PR as regression of measurable disease and no new sites.

  56 days

• Overall Response Rate (ORR)

  Percentage of participants with objective response defined as Complete (CR) and Partial (PR) Response. Computed tomography (CT) and Positron emission tomography (PET) scans done after every 2 cycles to assess efficacy using Cheson Criteria (2007) which lists CR as disappearance of all evidence of disease, and PR as regression of measurable disease and no new sites.

  Up to 12 cycles or 48 weeks

Study Arms (1)

AUY922

EXPERIMENTAL

AUY922 starting dose 70 mg/m2 intravenous on Days 1, 8, 15, and 22 of 28 day cycle.

Drug: AUY922

Interventions

AUY922 DRUG

Starting Dose: 70 mg/m2 by vein on days 1, 8, 15, and 22 days of a 28 day cycle.

AUY922

Eligibility Criteria

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

You may qualify if:

• Age \>/= 18 years
• Able to sign Informed Consent
• Patients must have the following laboratory values: Hematologic: Absolute Neutrophil Count (ANC) \>/=1.5x10\^9/L; Hemoglobin (Hgb) \>/=9 g/dl; Platelets (plt) \>/=50 x10\^9/L. Biochemistry: Potassium within normal limits; Total calcium (corrected for serum albumin) and Phosphorus within normal limits o Magnesium above LLN or correctable with supplements; Liver and Kidney Functions: aspartate aminotransferase (AST)/serum glutamate oxaloacetate transaminase (SGOT) and ALT/serum glutamate pyruvate transaminase (SGPT) \</=1.5 x Upper Limit of Normal (ULN) if Alkaline Phosphate (AP) \> 2.5 ULN AST/SGOT and ALT/SGPT \</=2.5 x Upper Limit of Normal (ULN) if Alkaline Phosphate (AP) \</=5.0 x ULN if liver metastases are present; Serum bilirubin \</= 1.5 x ULN; 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
• Histologically confirmed Diffuse Large B-cell Lymphoma (DLBCL), (primary mediastinal DLBCL, DLBCL-NOS, large B-cell transformation of indolent B-cell lymphoma including follicular lymphoma, small lymphocytic lymphoma and marginal zone lymphoma) or Peripheral T-cell Lymphoma (PTCL), including PTCL not otherwise specified, angioimmunoblastic lymphoma, anaplastic large T-cell lymphoma, hepatosplenic T-cell lymphoma, enteropathy associated T-cell lymphoma; nodal or extranodal NK/T-cell lymphoma, mycosis fungoides with radiographically measurable disease.
• Relapsed or refractory after standard treatments and with no curative option with conventional therapy.
• Measurable disease.
• No known evidence of cerebral or meningeal involvement by lymphoma.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

You may not qualify if:

• Diarrhea \> CTCAE (v4.02) grade 1 that cannot be controlled with oral anti-diarrhea medications.
• Pregnant or lactating women.
• Fertile women of childbearing potential (WCBP), a female that has not been surgically sterilized or that has not been amenorrheic for at least 24 consecutive months, 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 \</= 6 months prior to study start; History of heart failure or left ventricular (LV) dysfunction (LVEF \</=45%) by multigated radionuclide angiography (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.
• Continuation #4) 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 (2 consecutive reading \>140/90), 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.
• All lymphomas except for Diffuse Large B-cell Lymphoma (DLBCL) and Peripheral T-cell Lymphoma (PTCL).
• Chemotherapy or radiation therapy or other investigational agents within 3 weeks prior to entering the study.
• Previous radioimmunotherapy within 12 weeks.
• Patient with known HIV infection.
• Known active viral hepatitis.
• Any serious active disease or co-morbid condition, which in the opinion of the principle investigator, will interfere with the safety or with compliance with the study.
• Serious nonmalignant disease (e.g., congestive heart failure, hydronephrosis); active uncontrolled bacterial, viral, or fungal infections; or other conditions which would compromise protocol objectives in the opinion of the investigator.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Novartis: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Lymphoma

Interventions

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

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

Although the study surpassed the first futility endpoint for DLBCL cohort, it was terminated early due to limited responses and significant toxicities witnessed in the entire cohort of the study.

Results Point of Contact

• Title: Yasuhiro Oki, Associate Professor, Lymphoma/Myeloma
• Organization: The University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-792-7734

Study Officials

• Yasuhiro Oki, MD

  M.D. Anderson 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: November 29, 2011
• First Posted: December 5, 2011
• Study Start: August 1, 2012
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: January 23, 2017
• Results First Posted: January 23, 2017

Record last verified: 2015-12

Locations

US (1)