Cladribine with Simultaneous or Delayed Rituximab in Treating Patients with Hairy Cell Leukemia

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase IIBiomarker/Laboratory analysis, TreatmentActive18 and over09-C-0005
NCI-2013-01595, NCT00781235, P08372, NCT00923013

Trial Description


This randomized phase II trial studies cladribine with simultaneous or delayed rituximab to see how well they work in treating patients with hairy cell leukemia. Drugs used in chemotherapy, such as cladribine, 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. Monoclonal antibodies, such as rituximab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether cladribine is more effective with simultaneous or delayed rituximab in treating patients with hairy cell leukemia.

Further Study Information


I. To determine if hairy cell leukemia (HCL) minimal residual disease (MRD) differs at 6 months after cladribine with or without rituximab administered concurrently with cladribine.


I. To compare cladribine + rituximab vs. cladribine alone in terms of 1) initial MRD-free survival and disease-free survival, 2) response to delayed rituximab for relapse, to determine if early rituximab compromises later response, and 3) feasibility of administration as an outpatient by simultaneous rituximab beginning before the cladribine in nonrandomized HCL patients.

II. To determine if MRD levels and tumor markers (soluble CD25 and CD22) after cladribine and/or rituximab correlate with response and clinical endpoints.

III. To compare blood MRD-free survival in patients who receive cladribine and up to 2 courses of rituximab, with respect to whether the first (1st) course of rituximab was used simultaneous with cladribine.

IV. To determine, using MRD and tumor marker data, when bone marrow biopsy (BMBx) can be avoided in managing HCL.

V. To compare response and MRD after the 1st and second (2nd) courses of cladribine.

VI. To evaluate the effects of cladribine and rituximab on normal T- and B-cells.

VII. To enhance the study of HCL biology by cloning, sequencing and characterizing monoclonal immunoglobulin rearrangements.

VIII. To determine overall survival, particularly in patients with poor-prognosis HCL like variant HCL (HCLv).

IX. To correlate bone marrow magnetic resonance imaging (MRI) signal with bone marrow biopsy.

OUTLINE: Patients with classic or typical HCL are randomized to 1 of 2 treatment arms; patients with variant HCL are assigned to Arm III.

ARM I: Patients receive cladribine intravenously (IV) over 1-2 hours on days 1-5 and rituximab IV over 2 hours once weekly for 8 weeks. At least 6 months after treatment with cladribine, patients achieving MRD positivity may receive a second course of rituximab in the absence of unacceptable toxicity.

ARM II: Patients receive cladribine as in Arm I. At least 6 months after treatment with cladribine, patients achieving MRD positivity receive rituximab IV once weekly for 8 weeks in the absence of unacceptable toxicity. Beginning at least 6 months later, patients achieving MRD positivity may receive a second course of rituximab in the absence of unacceptable toxicity.

ARM III: Patients receive cladribine and rituximab as in Arm I.

After completion of study treatment, patients are followed up at 30 days, 9 weeks, every 3 months for 2 years, 2.5 years, and then periodically thereafter.

Eligibility Criteria

Inclusion Criteria:

Evidence of HCL by flow cytometry, reviewed by the Laboratory of Pathology, National Cancer Institute (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 (absolute neutrophil count [ANC] < 1000 cells/ul)

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

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

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

No prior purine analog therapy except up to 1 prior course of either cladribine or pentostatin

No prior rituximab unless HCLv patient

Eastern Cooperative Oncology Group (ECOG) performance status 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 =< 1.5 or creatinine clearance >= 60 ml/ml

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

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 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

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 New York Heart Association (NYHA) class III-IV heart disease

Known infection with human immunodeficiency virus (HIV); hepatitis B is allowed only if viral load is undetectable and if on anti-hepatitis B therapy like entecavir; hepatitis C is allowed only if viral load is undetectable, and if the patient has received curative therapy

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 cladribine (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 central nervous system (CNS) disease, which is symptomatic

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

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

Robert J. Kreitman
Principal Investigator

NCI - Center for Cancer Research

Robert J. Kreitman
Ph: 301-480-6187

Robert J. Kreitman
Principal Investigator

Link to the current record.
NLM Identifier NCT00923013

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