17-DMAG in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphomas

Study Overview
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Brief Summary
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This phase I trial is studying the side effects and best dose of 17-DMAG in treating patients with metastatic or unresectable solid tumors or lymphomas. Drugs used in chemotherapy, such as 17-DMAG, work in different ways to stop cancer cells from dividing so they stop growing or die

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in patients with metastatic or unresectable solid tumors or lymphomas. II. Determine the safety and toxicity of this drug in these patients. III. Determine the pharmacokinetics and pharmacodynamics of this drug in these patients. IV. Determine the recommended phase II dose of this drug for future studies. SECONDARY OBJECTIVES: I. Determine tumor response in patients treated with this drug. OUTLINE: This is a dose-escalation, multicenter study. Patients receive 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) IV over 1-6 hours on days 1-3 or 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 1-2 patients receive accelerated escalating doses of 17-DMAG until at least 1 of 2 patients experience dose-limiting toxicity (DLT). Cohorts are then expanded to 3-6 patients who receive escalating doses (in a standard manner) of 17-DMAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience DLT. Patients are followed at 4 weeks.

Official Title
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A Phase I Study Of 17-Dimethylaminoethylamino-17-Demethoxygeldanamycin, (17-DMAG) (NSC 707545) In Patients With Advanced Solid Tumors

Conditions
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Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Intraocular Lymphoma, Nodal Marginal Zone B-cell Lymphoma, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult T-cell Leukemia/Lymphoma, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent Small Lymphocytic Lymphoma, Splenic Marginal Zone Lymphoma, Stage III Adult Burkitt Lymphoma, Stage III Adult Diffuse Large Cell Lymphoma, Stage III Adult Diffuse Mixed Cell Lymphoma, Stage III Adult Diffuse Small Cleaved Cell Lymphoma, Stage III Adult Hodgkin Lymphoma, Stage III Adult T-cell Leukemia/Lymphoma, Stage III Cutaneous T-cell Non-Hodgkin Lymphoma, Stage III Grade 1 Follicular Lymphoma, Stage III Grade 2 Follicular Lymphoma, Stage III Grade 3 Follicular Lymphoma, Stage III Mantle Cell Lymphoma, Stage III Marginal Zone Lymphoma, Stage III Mycosis Fungoides/Sezary Syndrome, Stage III Small Lymphocytic Lymphoma, Stage IV Adult Burkitt Lymphoma, Stage IV Adult Diffuse Large Cell Lymphoma, Stage IV Adult Diffuse Mixed Cell Lymphoma, Stage IV Adult Diffuse Small Cleaved Cell Lymphoma, Stage IV Adult Hodgkin Lymphoma, Stage IV Adult T-cell Leukemia/Lymphoma, Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma, Stage IV Grade 1 Follicular Lymphoma, Stage IV Grade 2 Follicular Lymphoma, Stage IV Grade 3 Follicular Lymphoma, Stage IV Mantle Cell Lymphoma, Stage IV Marginal Zone Lymphoma, Stage IV Mycosis Fungoides/Sezary Syndrome, Stage IV Small Lymphocytic Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific, Waldenström Macroglobulinemia

Intervention / Treatment
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* Drug: alvespimycin hydrochloride
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed solid tumor or lymphoma Metastatic or unresectable disease Standard curative or palliative measures do not exist or are no longer effective No known brain metastases Performance status - ECOG 0-2 Performance status - Karnofsky 60-100% More than 12 weeks Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9.0 g/dL ALT and AST ≤ 1.5 times upper limit of normal (ULN) Bilirubin ≤ normal Creatinine ≤ 1.25 times ULN Creatinine clearance ≥ 60 mL/min QTc < 450 msec for male patients (470 msec for female patients) LVEF > 40% by MUGA No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row) No myocardial infarction or active ischemic heart disease within the past year No New York Heart Association class III or IV congestive heart failure No poorly controlled angina No uncontrolled dysrhythmia requiring medication No left bundle branch block No history of congenital long QT syndrome No other significant cardiac disease Pulse oximetry at rest or on exercise > 88% No symptomatic pulmonary disease (e.g., chronic obstructive or restrictive pulmonary disease, etc.) or any of the following are allowed: Pulmonary disease requiring medication History of dyspnea, dyspnea on exertion, or paroxysmal nocturnal dyspnea Patients meeting the Medicare criteria for home oxygen or are on oxygen Not pregnant or nursing Negative pregnancy test Fertile patients must use effective double barrier contraception 1 week before, during, and for at least 2 weeks after study participation No uncontrolled illness No active or ongoing infection No history of allergic reaction attributed to compounds of similar chemical or biological composition to 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) No psychiatric illness or social situation that would preclude study compliance No concurrent routine colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF]) At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered Concurrent hormonal therapy allowed At least 4 weeks since prior radiotherapy and recovered No prior radiation that included the heart in the field (e.g., mantle) No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent anticancer agents or therapies No concurrent medication that would prolong the QTc interval No other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (alvespimycin hydrochloride)<br>Patients receive 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) IV over 1-6 hours on days 1-3 or 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. | Drug: alvespimycin hydrochloride<br>* Given IV<br>* Other names: KOS-1022;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of alvespimycin hydrochloride |  | 21 days | 
| Toxicity graded using the NCI CTCAE version 3.0 |  | Up to 4 weeks | 
| Recommended phase II dose (RP2D) of alvespimycin hydrochloride for future studies determined by toxicity assessments |  | 21 days | 
| Pharmacokinetics of alvespimycin hydrochloride in blood, urine, and tumor tissue | Analyzed by both non-compartmental and compartmental methods. | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response assessed by tumor measurements |  | Up to 4 weeks |