A Study of the HSP90 Inhibitor AUY922

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01485536
• Collaborator: Novartis (Industry)
• Enrollment: 21
• Location: 1
• Arm: 1
• Duration (Months): 39
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: AUY922	Phase 2

Detailed Description

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 Days 1 and 15 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. On Day 1 of Cycle 1, this blood will also be used to check your heart function.

• You will have ECGs before and after the study drug infusion.

On Day 8 of Cycles 1-12:

• Your vital signs will be measured.

• 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 ECGs before and after the study drug infusion.

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 ECGs at about 24 and 48 hours after the end of the infusion.

• 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of the HSP90 Inhibitor AUY922 in Patients With Relapsed and Refractory Lymphoma
• Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AUY922 AUY922 starting dose 70 mg/m2 intravenous on Days 1, 8, 15, and 22 of 28 day cycle.	Drug: AUY922; Starting Dose: 70 mg/m2 by vein on days 1, 8, 15, and 22 days of a 28 day cycle.

Outcome Measures

Primary Outcome Measures

1. Objective Response in Participants With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL) and Peripheral T-cell Lymphoma (PTCL) [56 days]

   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.

2. Overall Response Rate (ORR) [Up to 12 cycles or 48 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Novartis

Investigators

• Principal Investigator: Yasuhiro Oki, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT01485536
• Other Study ID Numbers: 2011-0467; NCI-2012-00070
• First Posted: Dec 5, 2011
• Last Update Posted: Jan 23, 2017
• Last Verified: Dec 1, 2015

• Keywords provided by M.D. Anderson Cancer Center: Lymphoma; Relapsed/refractory lymphoma; AUY922
• Additional relevant MeSH terms: Lymphoma

Study Results

Participant Flow

Recruitment Details	Recruitment Period: August 28, 2016 to June 17, 2014. All recruitment done at The University of Texas MD Anderson Cancer Center.
Pre-assignment Detail	Of 26 participants screened for enrollment, five were not eligible therefore excluded from the study before any treatment assignment.

Arm/Group Title	AUY922
Arm/Group Description	AUY922 starting dose 70 mg/m2 intravenous on Days 1, 8, 15, and 22 of 28 day cycle.
Period Title: Overall Study
STARTED	21
COMPLETED	17
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	AUY922
Arm/Group Description	AUY922 starting dose 70 mg/m2 intravenous on Days 1, 8, 15, and 22 of 28 day cycle.
Overall Participants	21
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60
Gender (Count of Participants)
Female	5 23.8%
Male	16 76.2%
Race/Ethnicity, Customized (Count of Participants)
Asian	1 4.8%
Black	1 4.8%
Hispanic	13 61.9%
White	15 71.4%
Region of Enrollment (participants) [Number]
United States	21 100%
Baseline Lymphoma Diagnosis (Count of Participants)
DLBCL	14 66.7%
PTCL	6 28.6%
Unknown	1 4.8%

Outcome Measures

1. Primary Outcome

Title	Objective Response in Participants With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL) and Peripheral T-cell Lymphoma (PTCL)
Description	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.
Time Frame	56 days

Outcome Measure Data

Analysis Population Description

One participant withdrew therefore was not evaluable for the outcome and is excluded from analysis

Arm/Group Title	AUY922
Arm/Group Description	AUY922 starting dose 70 mg/m2 intravenous on Days 1, 8, 15, and 22 of 28 day cycle.
Measure Participants	20
DLBCL (N=14)	1 4.8%
PTCL (N=6)	1 4.8%

2. Primary Outcome

Title	Overall Response Rate (ORR)
Description	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.
Time Frame	Up to 12 cycles or 48 weeks

Outcome Measure Data

Analysis Population Description

One participant withdrew therefore was not evaluable for the outcome and is excluded from analysis

Arm/Group Title	AUY922
Arm/Group Description	AUY922 starting dose 70 mg/m2 intravenous on Days 1, 8, 15, and 22 of 28 day cycle.
Measure Participants	20
DLBCL (N=14)	7 33.3%
PTCL (N=6)	17 81%

Adverse Events

Time Frame	Adverse event data were collected through each four week cycle up to 12 cycles (48 weeks).
Arm/Group Title	AUY922
Arm/Group Description	AUY922 starting dose 70 mg/m2 intravenous on Days 1, 8, 15, and 22 of 28 day cycle.
All Cause Mortality
	AUY922
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	AUY922
	Affected / at Risk (%)	# Events
Total	4/20 (20%)
Gastrointestinal disorders
Diarrhea	1/20 (5%)	1
Vomiting/Diarrhea	1/20 (5%)	1
Infections and infestations
Pneumonia	1/20 (5%)	1
Sepsis	1/20 (5%)	1
Vascular disorders
Thrombocytopenia	1/20 (5%)	1
Other (Not Including Serious) Adverse Events
	AUY922
	Affected / at Risk (%)	# Events
Total	20/20 (100%)
Blood and lymphatic system disorders
Anemia	9/20 (45%)	16
Cardiac disorders
Atrial fibrillation	2/20 (10%)	2
Cardiac disorders - (Other)	1/20 (5%)	1
Sinus tachycardia	3/20 (15%)	3
Eye disorders
Blurred vision	1/20 (5%)	1
Dry eye	1/20 (5%)	1
Eye disorders - Impaired vision	7/20 (35%)	13
Flashing lights	1/20 (5%)	1
Floaters	1/20 (5%)	1
Night blindness	2/20 (10%)	2
Photophobia	1/20 (5%)	1
Watering eyes	1/20 (5%)	1
Gastrointestinal disorders
Abdominal pain	5/20 (25%)	6
Bloating	1/20 (5%)	1
Constipation	6/20 (30%)	6
Diarrhea	10/20 (50%)	23
Dry mouth	1/20 (5%)	1
Dysphagia	2/20 (10%)	2
Flatulence	1/20 (5%)	1
Gastritis	1/20 (5%)	1
Gastrointestinal disorders - (Other)	1/20 (5%)	2
Hemorrhoids	1/20 (5%)	1
Mucositis oral	1/20 (5%)	1
Oral pain	1/20 (5%)	2
Vomiting	6/20 (30%)	9
General disorders
Chills	1/20 (5%)	1
Edema limbs	6/20 (30%)	6
Fatigue	12/20 (60%)	21
Fever	3/20 (15%)	6
General disorders and administration site conditions - (Other)	6/20 (30%)	8
Malaise	1/20 (5%)	1
Nausea	9/20 (45%)	15
Pain	2/20 (10%)	2
Immune system disorders
Allergic reaction	1/20 (5%)	1
Infections and infestations
Eye infection	1/20 (5%)	1
Infections and infestations - (Other)	1/20 (5%)	1
Lip infection	1/20 (5%)	1
Lung infection	1/20 (5%)	1
Mucosal infection	2/20 (10%)	2
Penile infection	1/20 (5%)	1
Sepsis	1/20 (5%)	1
Upper respiratory infection	1/20 (5%)	1
Injury, poisoning and procedural complications
Bruising	1/20 (5%)	1
Investigations
Activated partial thromboplastin time prolonged	1/20 (5%)	1
Alanine aminotransferase increased	1/20 (5%)	1
Alkaline phosphatase increased	1/20 (5%)	1
Aspartate aminotransferase increased	1/20 (5%)	1
Blood bilirubin increased	1/20 (5%)	2
Creatinine increased	1/20 (5%)	1
Investigations - Neutropenia	1/20 (5%)	1
Neutrophil count decreased	5/20 (25%)	10
Platelet count decreased	8/20 (40%)	15
Weight loss	2/20 (10%)	2
Metabolism and nutrition disorders
Anorexia	2/20 (10%)	3
Dehydration	3/20 (15%)	4
Hypercalcemia	2/20 (10%)	2
Hyperglycemia	1/20 (5%)	1
Hypermagnesemia	1/20 (5%)	1
Hypoalbuminemia	2/20 (10%)	2
Hypocalcemia	1/20 (5%)	1
Hypoglycemia	2/20 (10%)	2
Hypokalemia	4/20 (20%)	5
Hypomagnesemia	9/20 (45%)	11
Hyponatremia	2/20 (10%)	2
Musculoskeletal and connective tissue disorders
Back pain	1/20 (5%)	1
Bone pain	2/20 (10%)	2
Buttock pain	3/20 (15%)	3
Chest wall pain	1/20 (5%)	1
Generalized muscle weakness	5/20 (25%)	7
Myalgia	1/20 (5%)	1
Pain in extremity	7/20 (35%)	7
Nervous system disorders
Dizziness	2/20 (10%)	2
Headache	4/20 (20%)	4
Nervous system disorders - Numbness & tingling feet	1/20 (5%)	1
Peripheral sensory neuropathy	5/20 (25%)	7
Syncope	1/20 (5%)	1
Psychiatric disorders
Anxiety	3/20 (15%)	3
Depression	1/20 (5%)	1
Insomnia	5/20 (25%)	5
Psychiatric disorders - (Other)	1/20 (5%)	1
Renal and urinary disorders
Urinary frequency	1/20 (5%)	1
Urinary tract infection	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	2/20 (10%)	2
Cough	7/20 (35%)	7
Dyspnea	4/20 (20%)	4
Epistaxis	2/20 (10%)	2
Hiccups	1/20 (5%)	1
Hoarseness	1/20 (5%)	1
Nasal congestion	3/20 (15%)	3
Pleural effusion	1/20 (5%)	1
Productive cough	5/20 (25%)	5
Respiratory failure	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders - Pneumonia	2/20 (10%)	2
Sinus disorder	1/20 (5%)	1
Sinusitis	1/20 (5%)	1
Sore throat	1/20 (5%)	1
Wheezing	2/20 (10%)	2
Skin and subcutaneous tissue disorders
Dry skin	1/20 (5%)	1
Erythema multiforme	2/20 (10%)	2
Pruritus	2/20 (10%)	3
Purpura	1/20 (5%)	1
Rash acneiform	1/20 (5%)	1
Rash maculo-papular	1/20 (5%)	1
Scalp pain	1/20 (5%)	1
Skin and subcutaneous tissue disorders - Lesions	2/20 (10%)	3
Social circumstances
Social circumstances - Cold Sweat	1/20 (5%)	1
Surgical and medical procedures
Surgical and medical procedures - Dental procedures	1/20 (5%)	1
Vascular disorders
Hypotension	4/20 (20%)	5

Limitations/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.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.