Randomized Phase II Trial of Rituximab With Either Pentostatin or Bendamustine for Multiply Relapsed or Refractory Hairy Cell Leukemia

* INCLUSION CRITERIA:
* Evidence of Hairy Cell Leukemia (HCL) by flow cytometry of blood or a solid (lymph node) mass, confirmed by the Laboratory of Pathology, National Cancer Institute (NCI), including positivity for cluster of Differentiation 19 (CD19), cluster of differentiation-22 (CD22), cluster of differentiate 20 (CD20), and Integrin, alpha X (CD11c). Patients with flow cytometry consistent with hairy cell leukemia-variant (HCLv) are eligible, including those with cluster of Differentiation 25 (CD25) and/or cluster of differentiation 103 (CD103) negative disease.
* bone marrow biopsy (BMBx) or bone marrow aspiration (BMA) consistent with HCL, confirmed by National Institutes of Health (NIH) Laboratory of Pathology, NCI, or the Department of Laboratory Medicine, Clinical Center, NIH, unless the diagnosis can be confirmed from a solid (lymph node) mass.
* 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 cladribine and no less than 4 weeks after other prior treatment, if applicable.

  * Neutropenia (Absolute neutrophil count (ANC) less than 1000 cells/microl).
  * Anemia (Hemoglobin (Hgb) less than 10g/dL).
  * Thrombocytopenia (Platelet (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 intravenous (i.v.) antibiotics.
  * Increasing lytic bone lesions

Patients who have eligible blood counts within 4 weeks from enrollment will not be considered ineligible if subsequent blood counts prior to enrollment fluctuate and become ineligible up until the time of enrollment.

* One of the following:

  * At least 2 prior courses of purine analog
  * 1 prior course of purine analog plus greater than or equal to1 course of rituximab if the response to the course of purine analog lasted less than 1 year.
  * Diagnosis of HCL variant (HCLv)
  * Unmutated (\>98% homology to germline) immunoglobulin heavy variable 4-34 (IGHV4-34+) expressing hairy cell leukemia (HCL)/HCLv
* Eastern Cooperative Oncology Group (ECOG) performance status (102) of 0-3
* Patients must be able to understand and give informed consent.
* Creatinine less than or equal to 1.5 or creatinine clearance greater than or equal to 60 ml/min.
* Bilirubin less than or equal to 2 unless consistent with Gilbert's (total/direct greater than 5), alanine transaminase (ALT) and aspartate aminotransferase (AST) less than or equal to 3 x 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, unless progressive disease more than 2 months after cladribine is documented.
* 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.
* Patients must be willing to co-enroll in the investigators companion protocol 10-C-0066 titled Collection of Human Samples to Study Hairy Cell and other Leukemias, and to Develop Recombinant Immunotoxins for Cancer Treatment.

EXCLUSION CRITERIA:

* Presence of active untreated infection
* Uncontrolled coronary disease or New York Heart Association (NYHA) class III-IV heart disease.
* Known infection with human immunodeficiency virus (HIV), hepatitis B or C.
* 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 central nervous system (CNS) disease
* Patients with history of non-response to both pentostatin plus rituximab and to bendamustine plus rituximab.
* 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 patients vaccination record and possible requirements be reviewed. 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.