Lower But More Frequent Dose Rituximab to Treat Chronic Lymphocytic Leukemia - Full Text View

Sponsor:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00366418

Purpose

This study will test the safety and effectiveness of using lower-dose rituximab given more frequently for treating chronic lymphocytic leukemia (CLL). Studies have shown that, used once a week for 4 weeks, rituximab was effective in up to 25 percent of patients with CLL. New evidence shows that using lower and more frequent doses of rituximab can be more effective in destroying leukemia cells and produce a better treatment response.

Patients 21 years of age and older with CLL who have received treatment with fludarabine may be eligible for this study.

Participants take rituximab for 12 weeks. One dose of the drug is infused through an arm vein over about 30 minutes on either day 1 (the first dose) or day 3 (the second dose). All other doses are given as an injection under the skin. After the first week, patients can choose to do these injections at home. Rituximab will be given 3 times a week for a total of 12 weeks. Other medications are given to reduce the side effects and allergic reactions to the drug. In addition to treatment, patients undergo the following tests and procedures:

Before treatment

Medical history, physical examination, electrocardiogram (EKG) and blood tests.
Bone marrow and lymph node biopsies (surgical removal of a small tissue sample).
Computed tomography (CT) and positron emission tomography (PET) scans. CT uses special x-rays to provide images of the neck, chest, abdomen and pelvis. PET uses a radioactive sugar to identify areas of disease.

During treatment (study weeks 1-12)

Medical history and physical examinations at weeks 3, 6 and 12 to evaluate drug side effects, plus weekly telephone checks and interim visits when needed.
Blood tests every other week to evaluate blood counts.

Evaluations after treatment (follow-up 3 months to 12 months)

Blood tests at follow-up visits at 3, 6, 9 and 12 months after treatment to evaluate blood counts.
Bone marrow aspiration and biopsy at 3 months after treatment to examine the effects of rituximab on bone marrow cells.
CT scans of the neck, chest, abdomen and pelvis at 3, 6, 9 and 12 months after treatment to evaluate the response to treatment.

Condition	Intervention	Phase
Refractory Chronic Lymphocytic Leukemia	Drug: Rituximab	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Pilot Study of Fractionated Dose Subcutaneous Rituximab (RTX, Rituxan(Registered Trademark)) in Patients With Refractory or Relapsed Chronic Lymphocytic Leukemia

Resource links provided by NLM:

MedlinePlus related topics: Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Rituximab

U.S. FDA Resources

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:

Safety profile and early evidence of efficacy of Rituxan give subcutaneously. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Measurement/deposition of serum compliment components, analysis of rituxan induced gene and protein expression in CLL cells, analysis and binding of rituximab to CLL cells. [ Time Frame: 1-12 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	12
Study Start Date:	August 2006
Study Completion Date:	June 2009
Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Intervention Details:

N/A

Detailed Description:

Rituximab is FDA approved for the treatment of relapsed or refractory low grade or follicular CD20+ B cell non Hodgkin's lymphoma (375 mg/m2 IV infusion once weekly for 4 or 8 doses). Recently, rituximab (anti CD20) has been introduced to CLL treatment regimens and has become an attractive choice in combination chemotherapy or as single agent treatment. Rituximab has been shown to be effective at lower doses than 375 mg/m2 when given more frequently.

Several theoretical considerations and supporting laboratory evidence suggest that a fractionated dosing schedule using low-dose rituximab could be more effective than the current i.v. schedule of high-dose rituximab. Indeed, preliminary clinical evidence suggests that low-dose rituximab at 20mg/m2 i.v. 3-times per week can lead to steady clearance of leukemic cells without inducing substantial loss of targeted CD20.

This is a Phase I/II , single agent study which will evaluate the safety and feasibility of subcutaneous rituximab (Rituxan) administered at 20 mg/day three times a week for 12 weeks in subjects with CLL. Patients need to have had prior treatment with fludarabine, and have an elevated absolute lymphocyte count. The primary objective will be to test the safety and feasibility of giving rituximab subcutaneously. We will also obtain as a secondary endpoint an early estimate of efficacy as evidenced by (a) shrinkage of lymphadenopathy and/or (b) improvement in blood values and bone marrow biopsy findings.

Eligibility

Ages Eligible for Study:	21 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

INCLUSION CRITERIA
Patients diagnosed with Chronic Lymphocytic Leukemia
Prior therapy with fludarabine or a fludarabine containing regimen
CD20 expression on CLL cells
Neutrophil count ANC greater than 500/mm(3)
Platelet count greater than 30K/mm(3)
Age 21-99

EXCLUSION CRITERIA

Bulky lymphadenopathy, defined as greater than 1 lymph node with greater than 5cm in largest diameter
Evidence for transformation into high grade lymphoma (Richter's transformation)
ECOG performance 3 or higher
Other concurrent anticancer therapies
Less than 3 months from last systemic therapy for CLL
Less than 6 months from last monoclonal antibody therapy
More than 10 doses rituximab, within 12 months preceeding protocol enrollment, either as single agent or in a combination chemotherapy regimen
Chronic or current clinically significant infection, including HIV positivity or hepatitis C
Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the patient's ability to tolerate protocol therapy
History of mucocutaneous reactions (paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis)
Known anaphylaxis or IgE mediated hypersensitivity to murine proteins or to any component of this product
Inability to self inject the study medication or to have it administered by a third person
Inability to understand the investigational nature of the study ability to provide informed consent

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00366418

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications:

Chiorazzi N, Rai KR, Ferrarini M. Chronic lymphocytic leukemia. N Engl J Med. 2005 Feb 24;352(8):804-15. Review. No abstract available.

Beum PV, Kennedy AD, Williams ME, Lindorfer MA, Taylor RP. The shaving reaction: rituximab/CD20 complexes are removed from mantle cell lymphoma and chronic lymphocytic leukemia cells by THP-1 monocytes. J Immunol. 2006 Feb 15;176(4):2600-9.

Kennedy AD, Beum PV, Solga MD, DiLillo DJ, Lindorfer MA, Hess CE, Densmore JJ, Williams ME, Taylor RP. Rituximab infusion promotes rapid complement depletion and acute CD20 loss in chronic lymphocytic leukemia. J Immunol. 2004 Mar 1;172(5):3280-8.

Responsible Party:	National Institutes of Health ( Georg Aue, M.D./National Heart, Lung, and Blood Institute )
Study ID Numbers:	060228, 06-H-0228
Study First Received:	August 17, 2006
Last Updated:	September 3, 2009
ClinicalTrials.gov Identifier:	NCT00366418 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

CLL
Monoclonal Antibody Therapy
Anti CD20
Biologic Response Modifier Therapy
Low Dose

Fractionated-Dose
Low-Dose
Chronic Lymphocytic Leukemia
CLL

Additional relevant MeSH terms:

Leukemia, Lymphoid
Neoplasms by Histologic Type
Immunoproliferative Disorders
Immune System Diseases
Immunologic Factors
Antineoplastic Agents
Rituximab
Physiological Effects of Drugs
Pharmacologic Actions

Leukemia
Lymphatic Diseases
Neoplasms
Leukemia, Lymphocytic, Chronic, B-Cell
Therapeutic Uses
Antirheumatic Agents
Leukemia, B-Cell
Lymphoproliferative Disorders

ClinicalTrials.gov processed this record on November 27, 2009