A Study of the HSP90 Inhibitor AUY922

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.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive AUY922 by vein over about 1 hour on Days 1, 8, 15, and 22 of each 28-day cycle.

Study Visits:

On Day 1 of Cycles 1-12:

• You will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate).
• Your performance status will be recorded.
• You will be asked about any drugs you may be taking and any side effects you may have had.
• Blood (about 6-7 teaspoons) will be drawn for routine tests and to check your heart function.
• You will have multiple ECGs over 8 hours.

On Day 1 of Cycles 1 and 2:

• Urine will be collected for routine tests.
• Blood (about 1 teaspoon) will be drawn to check your blood clotting function.

On Days 2 and 3 of Cycle 1:

• Blood (about 5-6 teaspoons) will be drawn for routine tests.
• You will have multiple ECGs over 24 hours.
• You will be asked about any drugs you may be taking, any side effects you may be having, and about your overall health.

On Day 8 of Cycles 1 and 2 and Day 15 of Cycles 1-12:

• Blood (about 5-6 teaspoons) will be drawn for routine tests.
• You will have multiple ECGs until 30 minutes after the infusion.
• Your vital signs will be measured.
• You will be asked about any drugs you may be taking, any side effects you may be having, and about your overall health.

On Day 22 of Cycle 1:

• You will have a physical exam, including measurement of your vital signs.
• Your performance status will be recorded.
• You will be asked about any drugs you may be taking, any side effects you may be having, and about your overall health.
• Blood (about 5-6 teaspoons) will be drawn for routine tests.

After every 2 cycles:

• You will have CT and PET scans to check the status of the disease.
• You will be asked about any side effects you may be having and about your overall health.

Anytime the study doctor thinks it is needed, you will have an eye exam or other tests.

Length of Study:

You may continue taking AUY922 for up to 12 cycles. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

End-of-Treatment Visit:

At 28 days after your last dose:

• Blood (about 5-6 teaspoons) and urine will be collected for routine tests.
• Blood (about 1 teaspoon) will be drawn to check your blood clotting function.
• You will have a physical exam, including measurement of your vital signs.
• Your performance status will be recorded.
• You will have an eye exam by an eye doctor.
• You will have CT and PET scans to check the status of the disease.
• You will be asked about any drugs you may be taking, any side effects you may be having, and about your overall health.

Long-Term Follow-Up:

After you stop the study drug, you will have a CT scan and physical exam every 3 months for 1 year, then every 4 months for another year, and every 6 months for 3 years and then 1 time a year after that.

This is an investigational study. AUY922 is not FDA approved or commercially available. It is currently being used for research purposes only.

Up to 42 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Age >/= 18 years
2. Able to sign Informed Consent
3. Patients must have the following laboratory values: Hematologic: Absolute Neutrophil Count (ANC) >/=1.5x10^9/L; Hemoglobin (Hgb) >/=9 g/dl; Platelets (plt) >/=75 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: AST/SGOT and ALT/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.
4. 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
5. 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.
6. Relapsed or refractory after standard treatments and with no curative option with conventional therapy.
7. Measurable disease.
8. No known evidence of cerebral or meningeal involvement by lymphoma.
9. ECOG performance status 0 to 2.

Exclusion Criteria:

1. Diarrhea > CTCAE (v4.02) grade 1 that cannot be controlled with oral anti-diarrhea medications.
2. Pregnant or lactating women.
3. 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.
4. 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 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.
5. 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;
6. Obligate use of a cardiac pacemaker.
7. All lymphomas except for Diffuse Large B-cell Lymphoma (DLBCL) and Peripheral T-cell Lymphoma (PTCL).
8. Chemotherapy or radiation therapy or other investigational agents within 3 weeks prior to entering the study.
9. Previous radioimmunotherapy within 12 weeks.
10. Patient with known HIV infection.
11. Known active viral hepatitis.
12. 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.
13. 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.