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Fludarabine, Cyclophosphamide, and Rituximab Versus Pentostatin, Cyclophosphamide, and Rituximab in Previously Untreated or Treated B-Cell Chronic Lymphocytic Leukemia Patients

This study has been completed.
Astex Pharmaceuticals
Information provided by (Responsible Party):
US Oncology Research Identifier:
First received: November 9, 2005
Last updated: May 19, 2014
Last verified: May 2014
The purpose of this research study is to find out what effects (good and bad) the combination of Nipent+Cytoxan+Rituxan has on CLL cancer compared to Fludara+Cytoxan+Rituxan. While all of these drugs are approved by the Food and Drug Administration (FDA) for the treatment of other cancers, these combinations are experimental for the treatment of CLL.

Condition Intervention Phase
B-Cell Chronic Lymphocytic Leukemia
Drug: Fludarabine
Drug: Cyclophosphamide
Drug: Rituximab
Drug: Pentostatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective, Randomized, Open Label, Phase III Trial of Fludarabine, Cyclophosphamide, and Rituximab vs. Pentostatin, Cyclophosphamide, and Rituximab in Previously Untreated or Treated B-cell Chronic Lymphocytic Leukemia

Resource links provided by NLM:

Further study details as provided by US Oncology Research:

Primary Outcome Measures:
  • Infection Rate [ Time Frame: 6 28-day cycles or 8 21-day cycles (depending on arm) or until PD, CR, or intolerable toxicity ] [ Designated as safety issue: Yes ]
    Febrile events requiring treatment. Febrile events are any temperature >= 101 F.; treatment is defined as the administration of IV or oral antibiotic therapy.

Secondary Outcome Measures:
  • Mean Absolute Neutrophil Count [ Time Frame: 2 months following last dose for both arms ] [ Designated as safety issue: Yes ]

Enrollment: 172
Study Start Date: December 2003
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Fludarabine, Cyclophosphamide, and Rituximab
Fludarabine, Cyclophosphamide, and Rituximab (dosage based on day in cycle)
Drug: Fludarabine Drug: Cyclophosphamide Drug: Rituximab
Experimental: Pentostatin, Cyclophosphamide, and Rituximab
Pentostatin, Cyclophosphamide, and Rituximab (dosage depends on day in cycle)
Drug: Cyclophosphamide Drug: Rituximab Drug: Pentostatin
Other Name: Nipent


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


Patients will be eligible for inclusion in this study if they meet all of the following criteria:

  • Progressive, histologically proven B-cell CLL.
  • Stage II, III, or IV B-cell CLL, as defined by Appendix III.

Note: The pathology or flow cytometry (of peripheral blood or a bone marrow) report, done by the local laboratory which documents these findings, must be included in the source documents. The SI must review the above pathology report or flow cytometry report results (including bone marrow aspirate analysis and CD5 and CD20 results) by fax, prior to registration, to confirm each patient's eligibility. Results should be consistent with typical B-cell CLL. If Dr. Reynolds is not available to review these documents, they must be reviewed by Dr. Nicholas J. Di Bella.

  • Patient must be CD20 +
  • Patient must be CD5+ (CD5 >70%)
  • No more than 1 prior course (regimen) of chemotherapy, which can include Fludara or Rituxan
  • No prior radiation therapy, except for the treatment of skin cancer or a nonmalignant condition.
  • If patient has lymph node involvement, a CT scan confirming measurable tumor size (lymph node must be >1 cm in its longest transverse diameter).
  • SI has been notified IF patient is on replacement steroids at time of registration.
  • Age greater than 18 years.
  • ECOG performance status of 0-2 (Appendix I).
  • Normal renal function (creatinine <1.5 mg/dL and BUN <25 mg/dL).
  • Absolute neutrophil count (ANC) greater than 1,000 cells/µL, platelet count greater than 50,000 cells/µL, and hemoglobin greater than 9 g/dL.
  • Bilirubin less than 2.0 mg/dL, and AST and ALT less than 5 times the upper limit of normal.
  • Negative serum pregnancy test within 7 days prior to registration (female patients of childbearing potential).
  • Agrees to use an acceptable method of birth control, if fertile patient (male or female), to avoid pregnancy for the duration of the study and for at least 3 months thereafter.
  • A signed Patient Informed Consent Form has been obtained.
  • A signed Patient Authorization Form has been obtained.


Patients will be excluded from this study if they meet any of the following criteria:

  • Any disease other than histologically confirmed progressive, Stage II, III, or IV CLL.
  • Well differentiated lymphocytic lymphoma in nodes without lymphocytosis.
  • More than 1 prior course (regimen) of chemotherapy.
  • Any radiation for the treatment of CLL.
  • Any prior Nipent.
  • Known to be CD20 negative (CD20 <20%).
  • Pregnant or lactating, or has a positive pregnancy test.
  • Has a history of other malignancy (other than in situ cervical cancer, carcinoma intraepithelial neoplasia, or non-melanoma skin cancer) within the last 5 years, which could affect the administration of these study drugs or assessment of current CLL.
  • Known to be HIV positive.
  • Uncontrolled thyroid disease or uncontrolled abnormal thyroid function.

Note: Patients with thyroid disease that is controlled with medication may participate.

  • A history of recent, unstable organic heart disease or stable organic heart disease with LVEF <50%.
  • A known hypersensitivity to Fludara, Nipent, Rituxan, or Cytoxan, or any component of these drugs.
  • Autoimmune hemolytic anemia.
  • Unable to comply with requirements of study.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00254163

United States, Florida
Cancer Centers of Florida, P.A.
Ocoee, Florida, United States, 34761
United States, Indiana
Hope Center
Terre Haute, Indiana, United States, 47802
United States, Maryland
Alliance Hematology Oncology PA
Westminster, Maryland, United States, 21157
United States, Missouri
St Joseph Oncology, Inc
St Joseph, Missouri, United States, 64507
United States, New York
New York Oncology Hematology, PC
Albany, New York, United States, 12208
United States, North Carolina
Northwestern Carolina Oncology Hemato
Hickory, North Carolina, United States, 28602
United States, Pennsylvania
Medical Oncology Associates
Kingston, Pennsylvania, United States, 18704
United States, Texas
South Texas Cancer Center-McAllen
McAllen, Texas, United States, 78503
Texas Oncology Cancer Center-Sugar Land
Sugar Land, Texas, United States, 77479
United States, Washington
Cancer Care Northwest-South
Spokane, Washington, United States, 99202
Yakima Valley Mem Hosp/North Star Lodge
Yakima, Washington, United States, 98902
Sponsors and Collaborators
US Oncology Research
Astex Pharmaceuticals
Principal Investigator: Craig Reynolds, MD US Oncology Research
  More Information

Responsible Party: US Oncology Research Identifier: NCT00254163     History of Changes
Other Study ID Numbers: 03017  NIP-03-007 
Study First Received: November 9, 2005
Last Updated: May 19, 2014
Health Authority: United States: Institutional Review Board

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
Adenosine Deaminase Inhibitors processed this record on October 21, 2016