Protocol for the Treatment of Patients With Previously Untreated 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. Identifier: NCT00280241
Recruitment Status : Completed
First Posted : January 20, 2006
Results First Posted : February 4, 2016
Last Update Posted : February 4, 2016
Genentech, Inc.
Information provided by (Responsible Party):
Michael Boyiadzis, University of Pittsburgh

Brief Summary:
This research study will look at the effects (good or bad) of administering cyclophosphamide, fludarabine, and rituximab. Clinical studies with combination therapy have shown higher response rates than using single drugs, and this study will evaluate the side effects and effectiveness of this combination.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Drug: Fludarabine Drug: Cyclophosphamide Drug: Rituximab Phase 2

Detailed Description:
This study is designed to expand on the highly successful combination of rituximab, fludarabine and cyclophosphamide for patients with previously untreated CLL. Responses in the range of 90-98% with 55% complete responses are reported. However, bone marrow toxicity has been a significant problem. This trial is designed to reduce the bone marrow toxicity by decreasing the doses of fludarabine and cyclophosphamide, but doubling the dose of rituximab with a maintenance dose of rituximab for up to two years, to maintain or even enhance efficacy.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 65 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Clinical Protocol for the Treatment of Patients With Previously Untreated Chronic Lymphocytic Leukemia
Study Start Date : June 2004
Primary Completion Date : February 2008
Study Completion Date : January 2013

Arm Intervention/treatment
Fludarabine is usually administered by IV infusion over 30 minutes or longer.
Drug: Cyclophosphamide
The dosage is a solution of 20 mg/mI. IV infusion over 1 hour.
Drug: Rituximab
First Infusion: The rituximab solution for infusion should be administered intravenously at an initial rate of 50 mg/hr. Subsequent rituximab infusions can be administered at an initial rate of 100 mg/hr, and increased by 100 mg/hr increments at 30-minute intervals, to a maximum of 400 mg/hr as tolerated.

Primary Outcome Measures :
  1. Tolerability of Rituximab, Cyclophosphamide and Fludarabine in Patients With Previously Untreated CLL/SLL [ Time Frame: Duration of treatment on study ]
    The number of patients who experience any grade 3-5 toxicity.

  2. Efficacy of Rituximab, Cyclophosphamide and Fludarabine in Patients With Previously Untreated CLL/SLL [ Time Frame: Three months after the sixth cycle (9 months) ]
    The number of patients who experience a complete clinical response.

Secondary Outcome Measures :
  1. Overall Survival Rate [ Time Frame: Five years after starting rituximab, cyclophosphamide and fludarabine ]
    The percentage of participants who are still alive.

  2. Duration of Response [ Time Frame: From complete response to the time of progressive disease, death or last clinical examination ]
    The length of time for which the complete response is maintained.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of CD20 + CLL
  • Peripheral blood absolute lymphocyte count of > 5,000/mm3 obtained within 2 weeks prior to randomization.
  • The lymphocytosis must consist of small to moderate size lymphocytes, with ≤55% (no greater than 55%) prolymphocytes, atypical lymphocytes, or lymphoblasts morphologically.
  • Phenotypically characterized CD20 + CLL defined as: 1) the predominant population of cells share B-cell antigens with CD5 in the absence of other pan-T-celI markers (CD3, CD2, etc.); 2) B-cell expresses either kappa or lambda light chains; and 3) surface immunoglobulin (slg) with low-cell surface density expression.
  • Splenomegaly, hepatomegaly or lymphadenopathy are not required for the diagnosis of CLL.
  • Must require chemotherapy. Indications for chemotherapy are one or more of the following:
  • One or more of the following disease-related symptoms
  • Weight loss >10% within the previous 6 months.
  • Fevers of greater than 100.0° F for 2 weeks without evidence of infection.
  • Night sweats without evidence of infection.
  • Evidence of progressive marrow failure as manifested by the development of or worsening of anemia (< 10 g/dl) and/or thrombocytopenia (< 100,000/mm3).
  • Massive (i.e., > 6 cm below left costal margin) or progressive splenomegaly.
  • Massive nodes or clusters (i.e., > 10 cm in longest diameter) or progressive
  • adenopathy.
  • Progressive lymphocytosis with an increase of> 50% over 2 month period, or an anticipated doubling time of less than 6 months.
  • NOTE: Marked hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for active disease are not sufficient for protocol therapy.
  • Serum creatinine <1.5 mg/dl.
  • Bilirubin must be <2 mg/dl, unless secondary to tumor, obtained within 2 weeks prior to randomization.
  • Age >18 years.
  • Not pregnant (confirmed by serum pregnancy test in females of reproductive potential) or breast feeding, because it is unknown what effect these drugs will have on children.
  • ECOG performance status 0-2.
  • AST or ATL >2x upper limit of normal unless related to CLL.
  • Subject has provided written informed consent.

Exclusion criteria:

  • Subjects with autoimmune anemia or thrombocytopenia are not eligible.
  • No prior cytotoxic chemotherapy. Patients with a history of steroid treatment for CLL, autoimmune hemolytic anemia, or autoimmune thrombocytopenia are not eligible.
  • Subjects with active infections requiring oral or intravenous antibiotics until resolution of the infection and completion of therapeutic antibiotics.
  • Women of childbearing potential and sexually active males who refuse to use an accepted and effective method of contraception.
  • Subjects with a second malignancy other than basal cell carcinoma of the skin or in situ carcinoma of the cervix are not eligible unless the tumor was treated with curative intent at least two years previously.
  • History of HIV
  • CNS disease
  • History of psychiatric disorder that would make it difficult to enroll and follow the patient on trial.
  • New York Heart Classification III or IV heart disease.
  • Hepatitis BsAg or Hepatitis C positive.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00280241

United States, Pennsylvania
Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
University of Pittsburgh
Genentech, Inc.
Principal Investigator: Micahel Boyiadzis, MD University of Pittsburgh

Responsible Party: Michael Boyiadzis, Study Principal Investigator, University of Pittsburgh Identifier: NCT00280241     History of Changes
Other Study ID Numbers: 03-136
First Posted: January 20, 2006    Key Record Dates
Results First Posted: February 4, 2016
Last Update Posted: February 4, 2016
Last Verified: January 2016

Keywords provided by Michael Boyiadzis, University of Pittsburgh:

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Fludarabine phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antiviral Agents
Anti-Infective Agents