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Lower But More Frequent Dose Rituximab to Treat Chronic Lymphocytic Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00366418
Recruitment Status : Completed
First Posted : August 21, 2006
Last Update Posted : July 2, 2017
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)

Tracking Information
First Submitted Date  ICMJE August 17, 2006
First Posted Date  ICMJE August 21, 2006
Last Update Posted Date July 2, 2017
Study Start Date  ICMJE August 10, 2006
Actual Primary Completion Date June 11, 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 20, 2010)
Safety profile and early evidence of efficacy of Rituxan given subcutaneously. [ Time Frame: 12 weeks ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2008)
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 ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Lower But More Frequent Dose Rituximab to Treat Chronic Lymphocytic Leukemia
Official Title  ICMJE A Pilot Study of Fractionated Dose Subcutaneous Rituximab (RTX, Rituxan(Registered Trademark)) in Patients With Refractory or Relapsed Chronic Lymphocytic Leukemia
Brief Summary

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.
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/m(2) 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/m(2) 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Refractory Chronic Lymphocytic Leukemia
Intervention  ICMJE Drug: Rituximab
Study Arms  ICMJE Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 25, 2009)
4
Original Enrollment  ICMJE
 (submitted: August 18, 2006)
12
Actual Study Completion Date  ICMJE June 11, 2009
Actual Primary Completion Date June 11, 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00366418
Other Study ID Numbers  ICMJE 060228
06-H-0228
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Not Provided
Original Responsible Party Same as current
Current Study Sponsor  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date February 23, 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP