Dose Escalation Study of Clofarabine in Patients With Relapsed or Refractory Low Grade or Intermediate-Grade B-Cell Lymphoma

Inclusion Criteria:

- Adult patients who are at least 18 years old

- Histologically confirmed low grade or intermediate-grade B-cell lymphoma

- Relapsed or refractory to at least one standard chemotherapy regimen. Patients who
have received Rituximab alone without having received a cytotoxic agent are not
eligible.

- Measurable disease, defined by the Cheson lymphoma criteria.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

- Life expectancy greater than 12 weeks

- Laboratory values obtained ≤2 weeks prior to entry

- Absolute neutrophil count (ANC) ≥ 1000 x 10 9/L

- White blood cell (WBC) count > 2.5 x 10 9/L

- Platelets ≥ 75 x 10 9/L

- Hemoglobin (Hg) > 9.0 g/dL

- Total bilirubin ≤2.0 mg/dL

- Aspartate transaminase (AST)/alanine transaminase (ALT) ≤3 × upper limit of
normal (ULN)

- Serum creatinine ≤2.0 mg/dL

- Normal cardiac function, defined as an ejection fraction ≥45% determined by
pretreatment radionuclide ventriculography (RVG) or echocardiogram.

- Capable of understanding the investigational nature, potential risks and benefits of
the study, and able to provide valid informed consent.

- Female patients of childbearing potential must have a negative serum pregnancy test
within 2 weeks prior to enrollment.

- Male and female patients must use an effective contraceptive method during the study
and for a minimum of 6 months after study treatment.

Exclusion Criteria:

- Previously untreated B-cell lymphoma.

- Received previous treatment with clofarabine.

- Patients with known AIDS-related or HIV-positive lymphoma.

- Autologous bone marrow or stem cell transplant within 6 months of study entry.

- Prior radiotherapy to the only site of measurable disease.

- Any medical condition that requires chronic use of oral high-dose corticosteroids
greater than 20 mg/day prednisone.

- Active autoimmune thrombocytopenia.

- Use of investigational agents within 30 days or any anticancer therapy within 3 weeks
before study entry. The patient must have recovered from all acute toxicities from
any previous therapy.

- Patients with an active, uncontrolled systemic infection considered to be
opportunistic, life threatening, or clinically significant at the time of treatment
or with a known or suspected fungal infection (ie, patients on parenteral antifungal
therapy).

- Active secondary malignancy.

- Pregnant or lactating patients.

- Any significant concurrent disease, illness, or psychiatric disorder that would
compromise patient safety or compliance, interfere with consent, study participation,
follow up, or interpretation of study results.

- Patients with active or untreated central nervous system (CNS) lymphoma.