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.
Sponsor:
Collaborator:
Astex Pharmaceuticals
Information provided by (Responsible Party):
US Oncology Research
ClinicalTrials.gov Identifier:
NCT00254163
First received: November 9, 2005
Last updated: September 15, 2016
Last verified: September 2016

November 9, 2005
September 15, 2016
December 2003
September 2011   (Final data collection date for primary outcome measure)
Infection Rate [ Time Frame: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity ]
infection=febrile events requiring treatment
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Complete list of historical versions of study NCT00254163 on ClinicalTrials.gov Archive Site
  • Infective Event Rate [ Time Frame: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity ]
    infective events=temperature >101 without symptoms or temp <101 with symptoms
  • Percentage of Patients Hospitalized [ Time Frame: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity ]
    Percentage of patients who were hospitalized due to any reasons during the study period.
  • Hematologic Recovery [ Time Frame: 2 months post-treatment ]
    defined as Hb >11g/dL and a platelet count >100 × 10^3/mm^3
  • Mean Absolute Neutrophil Count (ANC) at Post-treatment [ Time Frame: 2 months post-treatment ]
    mean Absolute Neutrophil Count (ANC) measured 2 months (8-10 weeks) following the last dose of study treatment
  • Complete Remission (CR) [ Time Frame: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity ]

    Definitions of response is evaluated using guidelines proposed by the National Cancer Institute-Sponsored Working Group for Chronic Lymphocytic Leukemia.

    Complete remission (CR) requires all of the following for a period of at least 2 months:

    1. Absence of lymphadenopathy by physical examination and appropriate radiographic techniques. Lymph nodes must be <1 cm.
    2. No evidence of hepatomegaly or splenomegaly.
    3. Absence of constitutional symptoms.
    4. Normal CBC as exhibited by:

      • Polymorphonuclear leukocytes ≥ 1,500/mm^3
      • Platelets > 100,000/mm^3
      • Hemoglobin > 11.0 g/dL (untransfused)
    5. Bone marrow aspirate and biopsy should be performed 2 months after clinical and laboratory results demonstrate that all of the requirements listed in 1-4 have been met to demonstrate that a CR has been achieved. The marrow sample must be at least normocellular for age, with less than 30% of the nucleated cells being lymphocytes.

    Lymphoid nodules should be absent.

  • Objective Remission Rate (ORR) [ Time Frame: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity ]

    Complete remission (CR) see Outcome Measure 6. Partial remission (PR) must exhibit criteria 1 and 2 as well as one or more of the remaining features for at least 2 months.

    1. ≥50% decrease in peripheral blood lymphocyte count from the pretreatment baseline value.
    2. ≥50% reduction in lymphadenopathy.
    3. ≥50% reduction in the size of the liver and/or spleen.
    4. Polymorphonuclear leukocytes ≥ 1,500/mm^3 or 50% improvement over baseline.
    5. Platelets >100,000/mm^3 or 50% improvement over baseline.
    6. Hemoglobin >11.0 g/dL or 50% improvement over baseline without transfusions. Nodular partial remission (nPR) is defined as a CR with persistent bone marrow nodules; Objective Remission (OR) = CR + PR + nPR.
  • Progression-free Survival (PFS) Rate at 1-year [ Time Frame: 12 months after registered. ]
    PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date
  • Progression-free Survival (PFS) Rate at 2-year [ Time Frame: 24 months after registered. ]
    PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date.
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Fludarabine, Cyclophosphamide, and Rituximab Versus Pentostatin, Cyclophosphamide, and Rituximab in Previously Untreated or Treated B-Cell Chronic Lymphocytic Leukemia Patients
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
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.
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Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
B-Cell Chronic Lymphocytic Leukemia
  • Drug: Fludarabine
  • Drug: Cyclophosphamide
  • Drug: Rituximab
  • Drug: Pentostatin
    Other Name: Nipent
  • Active Comparator: Fludarabine, Cyclophosphamide, and Rituximab
    Fludarabine, Cyclophosphamide, and Rituximab (dosage based on day in cycle)
    Interventions:
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
    • Drug: Rituximab
  • Experimental: Pentostatin, Cyclophosphamide, and Rituximab
    Pentostatin, Cyclophosphamide, and Rituximab (dosage depends on day in cycle)
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Rituximab
    • Drug: Pentostatin
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
184
September 2011
September 2011   (Final data collection date for primary outcome measure)

INCLUSION CRITERIA:

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.

EXCLUSION CRITERIA:

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.
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00254163
03017, NIP-03-007
No
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US Oncology Research
US Oncology Research
Astex Pharmaceuticals
Principal Investigator: Craig Reynolds, MD US Oncology Research
US Oncology Research
September 2016

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