Clinical trial NCT00254163: Fludarabine, Cyclophosphamide, and Rituximab Versus Pentostatin, Cyclophosphamide, and Rituximab in Previously Untreated or Treated B-Cell Chronic Lymphocytic Leukemia Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: B-Cell Chronic Lymphocytic Leukemia
Lead sponsor: US Oncology Research
Sponsor class: INDUSTRY
Collaborators: name: Astex Pharmaceuticals, Inc.
First posted: 2005-11-15
Enrollment: 184
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Infection Rate
timeFrame: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity
Secondary outcomes:
measure: Infective Event Rate
timeFrame: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity
measure: Percentage of Patients Hospitalized
timeFrame: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity
measure: Hematologic Recovery
timeFrame: 2 months post-treatment
measure: Mean Absolute Neutrophil Count (ANC) at Post-treatment
timeFrame: 2 months post-treatment
measure: Complete Remission (CR)
timeFrame: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity
measure: Objective Remission Rate (ORR)
timeFrame: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity
measure: Progression-free Survival (PFS) Rate at 1-year
timeFrame: 12 months after registered.
measure: Progression-free Survival (PFS) Rate at 2-year
timeFrame: 24 months after registered.
Other outcomes:
Locations:
city: Ocoee
country: United States
facility: Cancer Centers of Florida, P.A.
state: Florida
city: Terre Haute
country: United States
facility: Hope Center
state: Indiana
city: Westminster
country: United States
facility: Alliance Hematology Oncology PA
state: Maryland
city: St Joseph
country: United States
facility: St Joseph Oncology, Inc
state: Missouri
city: Albany
country: United States
facility: New York Oncology Hematology, PC
state: New York
city: Hickory
country: United States
facility: Northwestern Carolina Oncology Hemato
state: North Carolina
city: Kingston
country: United States
facility: Medical Oncology Associates
state: Pennsylvania
city: McAllen
country: United States
facility: South Texas Cancer Center-McAllen
state: Texas
city: Sugar Land
country: United States
facility: Texas Oncology Cancer Center-Sugar Land
state: Texas
city: Spokane
country: United States
facility: Cancer Care Northwest-South
state: Washington
city: Yakima
country: United States
facility: Yakima Valley Mem Hosp/North Star Lodge
state: Washington
Study officials:
affiliation: US Oncology Research
name: Craig Reynolds, MD
role: PRINCIPAL_INVESTIGATOR
References: