FCM-R (Fludarabine, Cyclophosphamide, Mitoxantrone, Rituximab) in Previously Untreated Patients With Chronic Lymphocytic Leukemia (CLL) < 70 Years
The goal of this clinical research study is to learn if using a combination of fludarabine, cyclophosphamide, and mitoxantrone plus rituximab, with the growth factor pegylated filgrastim, will improve the response to treatment, and increase the time this response lasts, for patients with previously untreated CLL. The safety of this combination will also be studied.
Chronic Lymphocytic Leukemia
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 2 Study of the Activity and Safety of Fludarabine, Cyclophosphamide, and Mitoxantrone Plus Rituximab (FCM-R) With Pegfilgrastim (Neulasta) as Frontline Therapy for Patients < 70 Years With Chronic Lymphocytic Leukemia|
- Clinical Response Rate (combined morphological [NCI WG criteria] + flow cytometry criteria) following treatment with FCM-R [ Time Frame: End of cycle 3 and 6. ] [ Designated as safety issue: No ]Courses will be repeated every 28 to 42 days (+/- 7 days) depending on recovery of peripheral blood counts and toxicities for a maximum of 6 courses. Patients will be evaluated for response after 3 and 6 courses. Bone marrow biopsies will be performed at the end of Cycles 3 and 6 of chemotherapy.
- Molecular response rate (PCR for IgH rearrangements) following treatment with FCM-R [ Time Frame: End of cycle 3 and 6. ] [ Designated as safety issue: No ]Courses will be repeated every 28 to 42 days (+/- 7 days) depending on recovery of peripheral blood counts and toxicities for a maximum of 6 courses. Patients will be evaluated for response after 3 and 6 courses. Bone marrow biopsies will be performed at the end of Cycles 3 and 6 of chemotherapy
|Study Start Date:||March 2005|
|Estimated Study Completion Date:||March 2015|
|Estimated Primary Completion Date:||March 2015 (Final data collection date for primary outcome measure)|
Experimental: FCM-R + Pegylated Filgrastim
Fludarabine 25mg/m2/day 2,3,4 i.v. 5-30 mins. Cyclophosphamide 250mg/m2/day 2,3,4 i.v. 5-30 mins. Mitoxantrone 6mg/m2/day 2 i.v. 30-60 mins. Rituximab 375mg/m2/day 1 i.v. 2-6 hours. Pegylated Filgrastim - 6mg on day 4,s.c.
Fludarabine 25mg/m2/day 2,3,4 i.v. 5-30 mins.
Other Name: Fludara®Drug: Cyclophosphamide
Cyclophosphamide 250mg/m2/day 2,3,4 i.v. 5-30 mins.
Other Name: Cytoxan®Drug: Mitoxantrone
Mitoxantrone 6mg/m2/day 2 i.v. 30-60 mins.
Other Name: Novantrone®Drug: Rituximab
Rituximab 375mg/m2/day 1 i.v. 2-6 hours
Other Name: Rituxan®Drug: Filgrastim
Pegylated Filgrastim - 6mg on day 4,s.c.
Other Name: Neupogen®
Fludarabine, cyclophosphamide, and mitoxantrone are chemotherapy drugs that are used in the treatment of CLL. Rituximab is a monoclonal antibody that binds to CLL cells and causes cell death. Pegfilgrastim (Neulasta) is a growth factor that helps the bone marrow to produce white cells (neutrophils) and is an approved drug to treat the suppression of marrow function caused by chemotherapy.
If you are eligible to take part in the study, you will begin treatment. Rituximab will be given through a needle in your vein (IV) on Day 1 of Courses 1-6. The first infusion may take up to 8 hours. For every dose of rituximab after that, the infusion may take 2-4 hours. The length of the infusion time depends on whether you have any reactions to the infusion. The dose level of rituximab may be increased for Cycles 2-6 as well. The drugs acetaminophen (Tylenol) and diphenhydramine hydrochloride (Benadryl) will be given before each 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 your time in the outpatient area may be longer if that occurs.
One day after the first dose of rituximab (Day 2), fludarabine and cyclophosphamide will be given by IV every day for 3 days (Days 2, 3, and 4), and mitoxantrone will be given by IV on Day 2. Fludarabine and cyclophosphamide will be given as 30-minute infusions, while the infusion of mitoxantrone will take 30-60 minutes. After the first treatment cycle, all the drugs will be given on Days 1, 2, and 3 for every cycle after that. Pegfilgrastim will be given as a subcutaneous injection (an injection under the skin) once per treatment cycle, right after you receive the last chemotherapy drug (in other words, on Day 4 during the first cycle, and on Day 3 for every cycle after that). Other IV fluids, such as saline, will be given on all of the treatment days to keep you hydrated, which means that each clinic visit will take about 6 hours. The combination will be repeated once every 4 to 6 weeks for a total of 6 courses.
The first treatment will be given at the UTMDACC outpatient clinic. The other 5 courses can be performed either at UTMDACC or at home with your regular physician.
During each treatment cycle, you will have blood samples (about 1 teaspoon each) drawn once every 1-2 weeks. Bone marrow biopsies will be performed at the end of Cycles 3 and 6 of chemotherapy.
With the exception of rituximab, the same doses of all other 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.
After Course 6 of chemotherapy is finished, you will have blood tests (about 2 teaspoons each) performed every 6-12 months.
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 and in this combination is considered investigational. Up to 30 patients will take part in the study. All will be enrolled at UTMDACC.
|United States, Texas|
|UT MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Stefan H Faderl, MD||M.D. Anderson Cancer Center|