Study of NRX 195183 Therapy for Patients With Relapsed or Refractory Acute Promyelocytic Leukemia

A common current therapeutic approach to APL uses oral ATRA and chemotherapy in induction
and consolidation. This approach has significantly improved survival in newly diagnosed APL
patients. However, approximately 30% of patients relapse. Recently, an approach involving
the combination of oral ATRA and arsenic trioxide has been tested. The prognosis for
relapsed patients is very poor. This study seeks to investigate NRX 195183 monotherapy in
patients who have failed or are resistant to or are intolerant of any prior therapy.

Inclusion Criteria:

- Clinical diagnosis of APL morphology or FAB M3 variant confirmed by RT-PCR assay or
chromosome analysis/FISH showing t(15:17) translocation. Patients must also have
relapse from, resistance to or intolerance of any one or more of the following
therapies:

- ATRA

- Cytotoxic chemotherapy

- Arsenic trioxide

- Patients must be 18 or older.

- Bilirubin equal or less than 1.5 times the upper limit of normal.

- Creatinine equal or less than 1.5 times the upper limit of normal.

- Patients entered into this study should be non-pregnant and non-nursing and should
not plan on becoming pregnant while on treatment. Treatment under this protocol would
expose an unborn child to significant risks. Women and men of reproductive potential
should agree to use an effective means of birth control. There is an extremely high
risk that a severely deformed infant will result if NRX 195183 is administered during
pregnancy.

Exclusion Criteria:

- Non-APL, AML patients should be excluded from the study.

- Other serious illnesses which would limit survival to 6 months.

- Psychiatric conditions which would prevent compliance with treatment or informed
consent.

- Uncontrolled or severe cardiovascular disease. This would include history of a recent
acute myocardial infarction, uncontrolled congestive heart failure, or active angina.

- AIDS or HIV positive patients, although HIV test is not required for accrual.