Imexon for Relapsed Follicular and Aggressive Lymphomas

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.

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
5. Serum bilirubin
6. Serum AST and ALT
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.