Imexon for Relapsed Follicular and Aggressive Lymphomas

Study Overview
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Brief Summary
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The purpose of this study is to determine whether Amplimexon (imexon for injection) is effective in the treatment of indolent and aggressive lymphomas that have progressed after treatment with standard therapies.

Detailed Description
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A phase II exploratory trial of imexon in lymphoma is justified by: (1) the observation of clinical activity (partial response to the drug observed in phase I testing in a subject with refractory indolent lymphoma); (2) the finding that imexon prevents the development of human immunoblastic lymphoma in SCID mice; (3) the finding that lymphoma cell lines are killed by readily achievable doses; and (4) translational studies implicating the importance of the redox state of the cancer cell. The dose and schedule chosen (1000 mg/m2 daily X 5 days every 3 weeks) is based on tolerability and subject acceptance in prior AmpliMed phase I studies. The planned correlative studies should help to identify potential biomarkers for response to imexon and provide further insight into potential mechanisms of imexon action hypothesized from results of prior laboratory studies.

Official Title
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A Phase II Study of Amplimexon® (Imexon for Injection) for the Treatment of Previously Treated Follicular and Aggressive Lymphoma in Adults

Conditions
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Follicular Lymphoma, Small Lymphocytic Lymphoma, Marginal Zone Lymphoma, Lymphoplasmacytic Lymphoma, Diffuse Large B Cell Lymphoma, Mantle Cell Lymphoma, Burkitt's Lymphoma

Intervention / Treatment
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* Drug: Imexon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis: Group 1: Histologically confirmed indolent NHL, including follicular (any grade), small lymphocytic lymphoma, marginal zone lymphoma and lymphoplasmacytic lymphomaGroup 2: histologically confirmed diffuse large B-cell, mantle cell, Burkitt, Burkitt-like, and diffuse large B-cell transformed from indolent non-Hodgkin's lymphoma. Prior treatment: Group 1: (indolent histologies): Patients must have demonstrated relapsed or refractory disease to 1 prior treatment regimen. The maximum number of prior regimens used for treatment is not specified. Group 2: (aggressive histologies): Patients must have demonstrated relapsed or refractory disease to at least 1 prior treatment regimen. In the case of de novo diffuse large B-cell lymphoma, prior treatment must include R-CHOP or R-CHOP-like therapy, as well as second line autologous stem cell transplantation unless the patient is not eligible. The maximum number of prior regimens is not specified. At least one target lesion, measurable by radiographic methods according to the 2007 Revised Response Criteria for Malignant Lymphoma. ECOG Performance Status 0-2. No clinical or laboratory evidence of central nervous system disease. Adult (age 18 years or older). Projected life expectancy >4 months. If female, neither pregnant (negative pregnancy test required at screening) nor lactating. If of child-bearing potential, must be able to use and agree to use medically acceptable contraception for the duration of the study. For female subjects who are neither post-menopausal nor surgically sterilized, this includes oral or injectable hormonal methods, barrier methods such as an intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence. Male subjects must also agree to use an acceptable method for contraception for the duration of the study. No major infection or serious uncontrolled concomitant disease. Fully recovered from any major surgery. No evidence of other concurrent active malignancy. At least 4 weeks since any prior cancer chemotherapy (2 weeks for corticosteroids), antibody therapy, or radiotherapy. Prior radiotherapy to less than an estimated 25% of the bone marrow. In addition, the target lesion(s) must not have been previously irradiated. Clinical laboratory values within the following limits: Hgb >/=10.0 g/dL Absolute neutrophil count ANC >/=1,500/mm3 Platelets >/=75,000/mm3 Serum creatinine </=2.0 times upper limit of normal Serum bilirubin </=2.0 times upper limit of normal Serum AST and ALT </=3 times upper limit of normal G6PD level >/= lower limit of normal Able and willing to render informed consent and to follow protocol requirements. Exclusion Criteria: Diagnosis of lymphoma based on fine needle aspirate. Curative therapy is indicated or possible. Absence of a measurable target lesion, or the only target lesion was previously irradiated. Symptoms, exam findings, or laboratory findings to suggest central nervous system disease involvement. Age < 18 years Projected life expectancy <4 months. Pregnant or lactating. Unable or unwilling to use medically acceptable contraception, if of childbearing potential. Evidence of major infection or other serious uncontrolled concomitant illness. Not fully recovered from prior major surgery. Evidence of other active malignancy. Prior radiotherapy, antibody therapy, or cancer chemotherapy within 4 weeks before start of treatment (2 weeks for corticosteroids). Prior radiotherapy to >25% of the bone marrow. Clinical laboratory values outside of permitted ranges. Respiratory insufficiency requiring oxygen therapy; angina at rest, or myocardial infarction in previous 3 months; history of life threatening ventricular arrhythmia; uncompensated CHF or NYHA Grade 3 or 4 cardiac disease. Unable or unwilling to give informed consent and to follow protocol requirements. Failure to meet any of the eligibility criteria.

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: Imexon<br>Subjects will be treated on Days 1-5 of 21-day treatment cycles for up to one year. Following pre-treatment with anti-emetics Amplimexon will be given by intravenous infusion over 60 minutes. | Drug: Imexon<br>* Amplimexon will be administered daily on Days 1-5 of 21-day treatment cycles as an intravenous infusion over a time course of 60 minutes. Subjects will receive 17 cycles of therapy for a total of one year on treatment. The Amplimexon starting dose for each subject in this study is 1000 mg/m² on each treatment day. Dose may be reduced by 25% for toxicity; after 2 dose reductions, subjects must be withdrawn from treatment.<br>* Other names: Amplimexon (imexon for injection);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate of of Participants to Imexon in the Treatment of Relapsed/Refractory Indolent and Aggressive Lymphomas | CT, PET, or MRI scans for the assessment of objective tumor responses were performed at baseline, after cycle 2, and every 3 cycles thereafter until disease progression. Standard response criteria from the International Harmonization Project on Lymphoma were used for classification of objective tumor responses. Response was defined as PR (Regression of measuable disease and no new sites) if >= 50% decrease in sum of the product of the diameters of up to 6 largest dominant masses; no increase in size of other nodes (a) [18F]fluorodeoxyglucose (FDG)-avid or PET prior to therapy; one or more (PET) positive at previously involved site (b) Variably FDG-avid or PET negative; regression on CT. | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Time to Progression Free Survival in Participants With Relapsed/Refractory Indolent and Aggressive Lymphomas | Measured from start of treatment until disease progression or death from any cause. | up to 25 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non Hodgkin's Lymphoma, Lymphoma, Low Grade, Lymphoma, Intermediate Grade, Lymphoma, High Grade, Lymphoma, B Cell