Rituximab and Pentostatin or Bendamustine Hydrochloride in Treating Patients with Relapsed or Refractory Hairy Cell Leukemia

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase IITreatmentActive18 and over10-C-0025
NCI-2013-01455, P09576, NCT01059786

Trial Description


This randomized phase II trial studies how well rituximab and pentostatin or bendamustine hydrochloride works in treating patients with hairy cell leukemia that has come back after a period of improvement or does not responded to treatment. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as pentostatin and bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether rituximab is more effective with pentostatin or bendamustine hydrochloride in treating recurrent hairy cell leukemia.

Further Study Information


I. To determine if pentostatin + rituximab and bendamustine (bendamustine hydrochloride) + rituximab are each associated with adequate response rates (overall response rate [ORR] = partial response [PR] + complete response [CR]) in patients with relapsed hairy cell leukemia (HCL), and, if so, to select which combination is likely to be superior.


I. To compare rituximab plus either pentostatin or bendamustine in terms of minimal residual disease (MRD)-free survival, disease-free survival, overall survival and toxicity, including to cluster of differentiation (CD)4+ T-cells.

II. To compare the 2 regimens in crossover when used after failure of the 1st regimen.

III. To determine if MRD levels and tumor markers (soluble CD25 and CD22, and real-time quantitative polymerase chain reaction [RQ-PCR]) correlate with response and clinical endpoints, and if bone marrow magnetic resonance imaging (MRI) signal correlates with bone marrow biopsy (BMBx) results, and whether these tests could in some cases possibly replace BMBx.

IV. To study the mechanism of thrombocytopenia after purine analog plus rituximab.

V. To study HCL biology by cloning, sequencing and characterizing monoclonal immunoglobulin rearrangements, and other genes.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive bendamustine hydrochloride intravenously (IV) over 30-60 minutes on days 1 and 2 and rituximab IV over 2 hours on days 1 and 15.

ARM II: Patients receive pentostatin IV over less than 45 minutes and rituximab IV over 2 hours on days 1 and 15.

In both arms, treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients in both arms who relapse, have no response, or have progressive disease may cross-over to the other arm.

After completion of study treatment, patients are followed up at 30 days, 4-6 weeks, every 3 months for 2 years, and then every 6 months thereafter.

Eligibility Criteria

Inclusion Criteria:

Evidence of 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 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

BMBx or bone marrow aspirate (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] < 1000 cells/ul)

Anemia (hemoglobin [Hgb] < 10g/dL)

Thrombocytopenia (platelets [Plt] < 100,000/ul)

Absolute lymphocyte count (ALC) of > 5,000 cells/uL

Symptomatic splenomegaly

Enlarging lymph nodes > 2 cm

Repeated infections requiring oral or i.v. antibiotics

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 >= 1 course of rituximab if the response to the course of purine analog lasted < 1 year

Diagnosis of HCL variant (HCLv)

Unmutated (> 98% homology to germline) IGHV4-34+expressing HCL/HCLv

Eastern Cooperative Oncology Group (ECOG) performance status of 0-3

Patients must be able to understand and give informed consent

Creatinine =< 1.5 or creatinine clearance >= 60 ml/min

Bilirubin =< 2 unless consistent with Gilbert’s (total/direct > 5)

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 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

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:

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 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 Contact Information

Trial Lead Organizations / Sponsors / Collaborators

NCI - Center for Cancer Research

  • National Cancer Institute
Robert J. Kreitman, Principal Investigator

Trial Sites



National Institutes of Health Clinical Center

Robert J. Kreitman
Ph: 301-480-6187
Email: kreitmar@mail.nih.gov

Robert J. Kreitman
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01059786

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.