Clinical trial NCT00794820: Fludarabine, Cyclophosphamide, and Rituximab - High Dose Frontline
Official title: Fludarabine, Cyclophosphamide, and Multiple Dose Rituximab as Frontline Therapy in Chronic Lymphocytic Leukemia (CLL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Keywords: Chronic Lymphocytic Leukemia
CLL
Leukemia
Fludarabine phosphate
Cyclophosphamide
Rituximab
FCR
Cytoxan®
Neosar®
Rituxan®
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2008-11-20
Enrollment: 66
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Primary Objective:

* To evaluate the efficacy (combined morphologic and flow remissions) of a combination of fludarabine, cyclophosphamide and multiple dose rituximab as frontline therapy for CLL.

Secondary Objective:

* To evaluate remission duration and survival.

Detailed description: DESCRIPTION OF RESEARCH

Fludarabine and cyclophosphamide are chemotherapy drugs that are used in the treatment of CLL. Rituximab is a monoclonal antibody that binds to lymphoma cells and causes cell death.

Before treatment starts, you will have a complete physical exam and routine blood tests (about 2 teaspoons). A bone marrow sample will be collected. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle. Women who are able to have children must have a negative blood or urine pregnancy test.

Rituximab will be given through a needle (IV) in a vein on Days 1, 2, and 3. One day after the first dose of rituximab (Day 2), fludarabine and cyclophosphamide will be given through a needle (IV) in a vein daily for 3 days (Days 2, 3, 4). After the first month, all the drugs will be given on Days 1, 2, 3. Other IV fluids such as saline will be given on all of the treatment days for hydration, which means that the daily visit will take about six hours. The combination will be repeated once every 4 to 6 weeks for a total of 6 courses.

The drugs acetaminophen (Tylenol) and diphenhydramine hydrochloride (Benadryl) will be given before the dose of rituximab. This will be done to decrease the risk of side effects. If side effects do occur during rituximab treatment, the drug may have to be stopped until the side effects go away and then restarted so the time in the outpatient area may be longer.

The first treatment will be given at M. D. Anderson. The other 5 courses can be performed ether at M. D. Anderson or at home with your regular physician.

The same doses of all three drugs will be used throughout the study unless side effects become severe. In that case, the dose may be lowered or the treatment may be stopped. You will be taken off study if the disease gets worse.

During treatments, patients will have blood samples (about 1 teaspoon each) taken once every 1-2 weeks. Bone marrow studies will be done at the end of the 3rd and 6th chemotherapy courses.

After treatment is completed, you will have blood tests (about 2 teaspoons each) done every 3 months for as long as you are in remission.

This is an investigational study. The FDA has approved all of the drugs used in this study and they are commercially available. However, their use in this study is investigational. As many as 64 patients will take part in the study. All will be enrolled at M. D. Anderson.

Eligibility criteria: Inclusion Criteria:

1. 16 years or older
2. Untreated CLL with indication for therapy or minimally treated (e.g. less than 1 month of steroids or chemotherapy) are eligible
3. Performance status of 3 or better (Appendix A)
4. Adequate renal and hepatic function (creatinine \<2 mg%, bilirubin \<2mg%). Patient with renal or liver dysfunction due to organ infiltration by lymphocytes may be eligible after discussion with the study chairman but upper limits for creatinine even under these circumstances would be creatinine \< 3 mg% and bilirubin \< 6 mg%. Patients with Gilbert's Syndrome may be entered on study with bilirubin 2-7 mg%..
5. A signed informed consent in keeping with policies of the hospital

Exclusion Criteria:

1) None

Primary outcomes:
measure: Complete Remission (CR) Rate of FCR3 in Treatment-naïve Participants With Chronic Lymphocytic Leukemia (CLL) at 6 Months
timeFrame: 6 months
Secondary outcomes:
measure: Remission Duration/Time to Progression (TTP)
timeFrame: 6 months to disease progression, period covered up to 12 years following treatment; Data cutoff for analysis was October 2014.
measure: Overall Survival (OS) Rate
timeFrame: 6 months to disease progression, period covered up to 12 years following treatment; Data cutoff for analysis was October 2014.
Other outcomes:
Locations:
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Susan O'Brien, M.D.
role: PRINCIPAL_INVESTIGATOR
References: