Randomized Trial of Cladribine (CdA) With Simultaneous or Delayed Rituximab to Eliminate Hairy Cell Leukemia Minimal Residual Disease

Inclusion Criteria

- INCLUSION CRITERIA:

Evidence of HCL by flow cytometry, reviewed by the Laboratory of Pathology, NCI, including
positivity for CD19, CD22, CD20, and CD11c.

BMBx consistent with HCL, reviewed by Laboratory of Pathology, NCI. BMBx may be negative
in HCLv in patients with increasing peripheral blood HCLv cells and spleen size.

Treatment indicated based on demonstration of at least one of the following no more than 4
weeks from the time of enrollment, and no less than 6 months after prior purine analog and
no less than 4 weeks after other prior treatment, if applicable.

- Neutropenia (ANC less than 1000 cells/microl).

- Anemia (Hgb less than 10g/dL).

- Thrombocytopenia (Plt less than 100,000/microl).

- Absolute lymphocyte count (ALC) of greater than 5,000 cells/microL

- Symptomatic splenomegaly.

- Enlarging lymph nodes greater than 2cm.

- Repeated infections requiring oral or i.v. antibiotics.

No prior purine analog therapy except up to 1 prior course of cladribine.

No prior rituximab unless HCLv patient.

ECOG performance status (70) of 0-3.

Patients must be able to understand and give informed consent.

Women of child-bearing age and all men must use birth control of any type until at least
12 months after the last dose of therapy.

Creatinine less than or equal to 1.5 or creatinine clearance greater than or equal to 60
ml/ml.

Bilirubin less than or equal to 2 unless consistent with Gilbert's (total/direct greater
than 5), ALT and AST less than or equal to 2.5 times upper limits of normal.

No other therapy (i.e. chemotherapy, interferon) for 4 weeks prior to study entry, or
cladribine for 6 months prior to study entry.

Age at least 18

Men and women of reproductive potential must agree to use an acceptable method of birth
control during treatment and for twelve months after completion of treatment.

Subject has provided written informed consent

EXCLUSION CRITERIA:

Presence of active untreated infection

Uncontrolled coronary disease or NYHA class III-IV heart disease.

Known infection with HIV, hepatitis B or C.

Patients with documented history of no response to cladribine, and without 50% improvement
in platelets, hemoglobin or granulocytes. This exclusion does not apply to HCLv. These
patients are eligible regardless of prior response to CDA.

Pregnant or lactating women.

Presence of active 2nd malignancy requiring treatment. 2nd malignancies with low activity
which do not require treatment (i.e. low grade prostate cancer, basal cell or squamous
cell skin cancer) do not constitute exclusions.

Inability to comply with study and/or follow-up procedures.

Presence of CNS disease

At the Investigator's discretion, receipt of a live vaccine within 4 weeks prior to
randomization. Efficacy and/or safety of immunization during periods of B-cell depletion
have not been adequately studied. It is recommended that a patient's vaccination record
and possible requirements be reviewed. Per the investigator's discretion, the patient may
have any required vaccination/booster administered at least 4 weeks prior to the
initiation of study treatment. Review of the patient's immunization status for the
following vaccinations is recommended: tetanus; diphtheria; influenza; pneumococcal
polysaccharide; Varicella; measles, mumps and rubella (MMR); and hepatitis B. Patients who
are considered to be at high risk for hepatitis B virus (HBV) infection and for whom the
investigator has determined that immunization is indicated should complete the entire HBV
vaccine series at least 4 weeks prior to participation in the study.