Imexon for Relapsed Follicular and Aggressive Lymphomas
Condition: Follicular Lymphoma; Small Lymphocytic Lymphoma; Marginal Zone Lymphoma; Lymphoplasmacytic Lymphoma; Diffuse Large B Cell Lymphoma; Mantle Cell Lymphoma; Burkitt's Lymphoma
MeSH terms: Burkitt Lymphoma; Lymphoma; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Leukemia, Lymphocytic, Chronic, B-Cell; Waldenstrom Macroglobulinemia
Intervention: Imexon
Intervention description: 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 Dose may be reduced by 25% for toxicity; after 2 dose reductions, subjects must be withdrawn from treatment.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non Hodgkin's Lymphoma; Lymphoma, Low Grade; Lymphoma, Intermediate Grade; Lymphoma, High Grade; Lymphoma, B Cell

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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.

          2. 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.

          3. At least one target lesion, measurable by radiographic methods according to the 2007
             Revised Response Criteria for Malignant Lymphoma.

          4. ECOG Performance Status 0-2.

          5. No clinical or laboratory evidence of central nervous system disease.

          6. Adult (age 18 years or older).

          7. Projected life expectancy >4 months.

          8. If female, neither pregnant (negative pregnancy test required at screening) nor
             lactating.

          9. 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.

         10. No major infection or serious uncontrolled concomitant disease. Fully recovered from
             any major surgery.

         11. No evidence of other concurrent active malignancy.

         12. At least 4 weeks since any prior cancer chemotherapy (2 weeks for corticosteroids),
             antibody therapy, or radiotherapy.

         13. Prior radiotherapy to less than an estimated 25% of the bone marrow. In addition, the
             target lesion(s) must not have been previously irradiated.

         14. Clinical laboratory values within the following limits:

               1. Hgb >/=10.0 g/dL

               2. Absolute neutrophil count ANC >/=1,500/mm3

               3. Platelets >/=75,000/mm3

               4. Serum creatinine </=2.0 times upper limit of normal

               5. Serum bilirubin </=2.0 times upper limit of normal

               6. Serum AST and ALT </=3 times upper limit of normal

         15. G6PD level >/= lower limit of normal

         16. Able and willing to render informed consent and to follow protocol requirements.

        Exclusion Criteria:

          1. Diagnosis of lymphoma based on fine needle aspirate.

          2. Curative therapy is indicated or possible.

          3. Absence of a measurable target lesion, or the only target lesion was previously
             irradiated.

          4. Symptoms, exam findings, or laboratory findings to suggest central nervous system
             disease involvement.

          5. Age < 18 years

          6. Projected life expectancy <4 months.

          7. Pregnant or lactating.

          8. Unable or unwilling to use medically acceptable contraception, if of childbearing
             potential.

          9. Evidence of major infection or other serious uncontrolled concomitant illness. Not
             fully recovered from prior major surgery.

         10. Evidence of other active malignancy.

         11. 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.

         12. Clinical laboratory values outside of permitted ranges.

         13. 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.

         14. Unable or unwilling to give informed consent and to follow protocol requirements.

         15. Failure to meet any of the eligibility criteria.