| Randomized Phase II Trial of Rituximab With Either Pentostatin or Bendamustine for Multiply Relapsed or Refractory Hairy Cell Leukemia
Basic Trial Information
Summary Background:
Objectives:
Eligibility:
Design:
Further Study Information Background: -Hairy cell leukemia (HCL) is highly responsive to purine analogs cladribine and pentostatin, without evidence of cure. Neither is standard after 2 courses, due to cumulative marrow and T-cell toxicity and declining remission rates and durations. Once resistant, patients after multiple relapses can die of disease-related cytopenias.
Objectives:
--To determine if pentostatin + rituximab and bendamustine + rituximab are each associated with adequate response rates (ORR=PR+CR) in patients with relapsed HCL, and, if so, to select which combination is likely to be superior.
Eligibility: HCL needing therapy, either greater than or equal to 2 prior courses of purine analog, or 1 course purine analog plus greater than or equal to 1 course rituximab if less than 1 year response to the 1 course purine analog. Prior treatment, ineligibility for, or patient refusal of recombinant immunotoxin. Design:
1. 28 patients to bendamustine 90 mg/m(2)/day, days 1 and 2 each cycle 2. 28 patients to pentostatin 4 mg/m(2) days 1 and 15 of each cycle.
--If > 14/28 respond, can conclude with 90% power that response > 40% in that arm. > 80% probability of selecting the better arm if true response probability is approximately 40-50% on the inferior arm and > 15% higher on the superior arm.
Eligibility Criteria
2.1.1.1. Evidence of HCL by flow cytometry of blood, reviewed by the Laboratory of Pathology, NCI, including positivity for CD19, CD22, CD20, and CD11c. Patients with flow cytometry consistent with HCL variant (HCLv) are eligible, including those with CD25 and/or CD103 negative disease. 2.1.1.2. BMBx consistent with HCL, reviewed by NIH Laboratory of Pathology, NCI, or the Department of Laboratory Medicine, Clinical Center, NIH. 2.1.1.3. 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. (Bullet) Neutropenia (ANC less than 1000 cells/microl). (Bullet) Anemia (Hgb less than 10g/dL). (Bullet) Thrombocytopenia (Plt less than 100,000/microl). (Bullet) Absolute lymphocyte count (ALC) of greater than 5,000 cells/microL (Bullet) Symptomatic splenomegaly. (Bullet) Enlarging lymph nodes greater than 2cm. (Bullet) Repeated infections requiring oral or i.v. antibiotics. 2.1.1.4. One of the following: (Bullet) At least 2 prior courses of purine analog (Bullet) 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. 2.1.1.5. ECOG performance status (98) of 0-3. 2.1.1.7. Patients must be able to understand and give informed consent. 2.1.1.8. Creatinine less than or equal to 1.5 or creatinine clearance greater than or equal to 60 ml/ml. 2.1.1.9. 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 x upper limits of normal. 2.1.1.10. No other therapy (i.e. chemotherapy, interferon) for 4 weeks prior to study entry, or cladribine for 6 months prior to study entry. 2.1.1.11. Age at least 18 2.1.1.12. 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. EXCLUSION CRITERIA: 2.1.2.1. Presence of active untreated infection 2.1.2.2. Uncontrolled coronary disease or NYHA class III-IV heart disease. 2.1.2.3. Known infection with HIV, hepatitis B or C. 2.1.2.4. Pregnant or lactating women. 2.1.2.5. 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. 2.1.2.6. Inability to comply with study and/or follow-up procedures. 2.1.2.7. Presence of CNS disease 2.1.2.8. Patients with history of non-response to both pentostatin plus rituximab and to bendamustine plus rituximab. 2.1.2.9. 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. 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. Trial Lead Organizations/Sponsors National Cancer Institute
Trial Sites
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