Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

FCM-R (Fludarabine, Cyclophosphamide, Mitoxantrone, Rituximab) in Previously Untreated Patients With Chronic Lymphocytic Leukemia (CLL) < 70 Years

This study is ongoing, but not recruiting participants.
OSI Pharmaceuticals
Genentech, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center Identifier:
First received: November 14, 2005
Last updated: February 17, 2015
Last verified: February 2015

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.

Condition Intervention Phase
Chronic Lymphocytic Leukemia
Drug: Fludarabine
Drug: Cyclophosphamide
Drug: Mitoxantrone
Drug: Rituximab
Drug: Filgrastim
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • 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.

Secondary Outcome Measures:
  • 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

Estimated Enrollment: 30
Study Start Date: March 2005
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Fludarabine
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®

Detailed Description:

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 MD Anderson.


Ages Eligible for Study:   up to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Untreated CLL, CLL/PLL, or SLL (small lymphocytic lymphoma) with indication for therapy (Indications for therapy include at least one of the following: i) one or more disease-related symptoms [fever, night sweats, weight loss, pronounced fatigue]; ii) advanced stage disease (Rai stage >/= 3 or Binet stage C); iii) autoimmune anemia and/or thrombocytopenia that is unresponsive to other therapies; iv) massive or progressive hepatomegaly and/or splenomegaly and/or lymphadenopathy; iv) recurrent infections; v) rapid lymphocyte doubling time of < 6 months).
  2. Age < 70 years.
  3. Adequate liver function (total bilirubin </= 2.5 mg/dL, SGPT </=4 x ULN) and renal function (serum creatinine </= 2.0 mg/dL). Patients with renal or liver dysfunction due to suspected organ infiltration by lymphocytes may be eligible after discussion with the Principal Investigator, but upper limits for creatinine even under these circumstances must be creatinine < 3mg/dL and bilirubin < 6 mg/dL. Patients with Gilbert's syndrome may be entered on study with bilirubin levels </= 4 mg/dL.
  4. Beta-2-microglobulin </= 4 mg/dL.
  5. ECOG performance status </= 2.
  6. Signed informed consent in keeping with the policies of the hospital.
  7. Male and female patients who are fertile agree to use an effective barrier method of birth control (ie, latex condom, diaphragm, cervical cap, etc) to avoid pregnancy. Female patients of childbearing potential (non-childbearing is defined as >/= 1 year postmenopausal or surgically sterilized) need a negative serum or urine pregnancy test within 14 days of study enrollment.

Exclusion Criteria:

  1. Active hepatitis B (at least one of the following markers positive: HBsAg, HBeAg, IgM anti-HBc, HBV DNA).
  2. Concurrent chemotherapy or immunotherapy.
  3. Pregnant patients.
  4. History of HIV
  5. Symptomatic CNS disease
  6. Symptomatic heart disease (NYHA class >/= 3) or LV ejection fraction < 40% (by MUGA or echocardiogram)
  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: NCT00254410

United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
OSI Pharmaceuticals
Genentech, Inc.
Principal Investigator: William G. Wierda, MD, PHD, BS M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00254410     History of Changes
Other Study ID Numbers: 2005-0106, NCI-2010-00437
Study First Received: November 14, 2005
Last Updated: February 17, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Chronic Lymphocytic Leukemia
Pegylated Filgrastim

Additional relevant MeSH terms:
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Fludarabine phosphate
Adjuvants, Immunologic
Alkylating Agents
Anti-Infective Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antiviral Agents
Central Nervous System Agents
Enzyme Inhibitors
Immunologic Factors processed this record on February 25, 2015