Protocol Number: 09-C-0005

Title:

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

Number:

09-C-0005

Summary:

Background:

- Cladribine is very effective in treating hairy cell leukemia, but it is not known if it can cure the disease.

- Rituximab is a monoclonal antibody that binds to the hairy cells and may kill them either by causing the cells to kill themselves or by getting the immune system to kill the cells. Rituximab is effective in hairy cell leukemia but is not considered standard treatment. Rituximab is approved by the Food and Drug Administration to treat patients with follicular non-Hodgkin's Lymphoma and diffuse large B-cell non-Hodgkin's lymphoma and for certain patients with rheumatoid arthritis.

Objectives:

- To determine if cladribine and rituximab, whether given together or with rituximab given 6 months after cladribine, is effective in treating residual hair cell leukemia (disease that remains after the original treatment).

Eligibility:

- Patients 18 years of age and older with hair cell leukemia.

- Patients who have received no more than one prior course of cladribine and no prior treatment with rituximab.

Design:

- It is believed that Rituximab may improve the activity of cladribine in cladribine, but it is unknown whether it would help most to add it at the beginning or wait until 6 months when the cladribine has had a full chance to work. Therefore, patients are randomly assigned to receive rituximab at the same time as cladribine or to receive the rituximab at least 6 months after cladribine (and only if hairy cells are present in a blood or bone marrow biopsy).

- Patients receive the initial treatment during a 5- to 7-day hospitalization at the NIH Clinical Center. Cladribine is given by vein over 2 hours every day for 5 days. Rituximab is given through a vein over 2 hours (or longer, if needed) once a week for 8 weeks.

- Patients have several lab tests, including bone marrow biopsies and blood tests, to determine whether they have hairy cells left during or after treatment.

- CT or other imaging study of the spleen and any other site of disease at 1 and 6 months after cladribine; before and 6 months after beginning delayed rituximab, yearly for 4 years while in complete remission, then every 2 years after that while in complete remission.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Evidence of HCL by flow cytometry of blood, 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.

Treatment indicated based on one of the following:

-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 20,000 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.

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.

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; diptheria; influenza; pneumoccocal 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.

Special Instructions:

Currently Not Provided

Keywords:

Hairy Cell Leukemia

Cladribine

Rituximab

Minimal Residual Disease

Recruitment Keyword(s):

Leukemia

Hairy Cell Leukemia

Condition(s):

Hairy Cell Leukemia

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

Drug: Cladribine

Drug: Rituximab

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s):

Bouroncle BA. Thirty-five years in the progress of hairy cell leukemia. Leuk Lymphoma. 1994;14 Suppl 1:1-12. Review.

Kreitman RJ, Cheson BD. Malignancy: Current Clinical Practice: Treatment of Hairy Cell Leukemia at the Close of the 20th Century. Hematology. 1999;4(4):283-303.

Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66.

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