A Study of the HSP90 Inhibitor AUY922
Condition: Lymphoma
MeSH terms: Lymphoma
Intervention: AUY922
Intervention description: Starting Dose: 70 mg/m2 by vein on days 1, 8, 15, and 22 days of a 28 day cycle.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lymphoma; Relapsed/refractory lymphoma; AUY922

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.
    

Eligibility criteria:

        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) >/=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.

          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. Eastern Cooperative Oncology Group (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
             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.

          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.