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Fludarabine, Cyclophosphamide, and Rituximab - High Dose Frontline

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00794820
Recruitment Status : Completed
First Posted : November 20, 2008
Results First Posted : August 23, 2016
Last Update Posted : May 8, 2018
Genentech, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Drug: Fludarabine Phosphate Drug: Cyclophosphamide Drug: Rituximab Phase 2

Detailed Description:


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a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle.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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 66 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Fludarabine, Cyclophosphamide, and Multiple Dose Rituximab as Frontline Therapy in Chronic Lymphocytic Leukemia (CLL)
Study Start Date : December 2003
Actual Primary Completion Date : December 2014
Actual Study Completion Date : December 2014

Arm Intervention/treatment
Experimental: FCR-Multiple Dose Rituximab
Fludarabine phosphate + Cyclophosphamide + Rituximab
Drug: Fludarabine Phosphate
25 mg/m^2 by vein over 5-30 minutes daily for 3 days (days 2-4)
Other Names:
  • Fludara®
  • Fludarabine

Drug: Cyclophosphamide
250 mg/m^2 by vein over 60 minutes daily for 3 days (days 2-4)
Other Names:
  • Cytoxan®
  • Neosar®

Drug: Rituximab
375 mg/m^2 by vein for dose 1 (given 1 day prior to chemotherapy) and then 500 mg/m^2 on days 2-3
Other Name: Rituxan®

Primary Outcome Measures :
  1. Complete Remission (CR) Rate of FCR3 in Treatment-naïve Participants With Chronic Lymphocytic Leukemia (CLL) at 6 Months [ Time Frame: 6 months ]
    CR Rate is defined as number of all treated participants with CR as defined by 2008 IWCLL update of NCI-WG response criteria: Complete remission (CR), requiring absence of peripheral blood clonal lymphocytes by immunophenotyping, absence of lymphadenopathy, absence of hepatomegaly or splenomegaly, absence of constitutional symptoms and satisfactory blood counts; Complete remission with incomplete marrow recovery (CRi), defined as CR above, but without normal blood counts; Partial remission (PR), defined as ≥ 50% fall in lymphocyte count, ≥ 50% reduction in lymphadenopathy or ≥ 50% reduction in liver or spleen, together with improvement in peripheral blood counts; Progressive disease (PD): ≥ 50% rise in lymphocyte count to > 5 x109/L, ≥ 50% increase in lymphadenopathy, ≥ 50% increase in liver or spleen size, Richter's transformation, or new cytopenias due to CLL; Stable disease, defined as not meeting criteria for CR, CRi, PR or PD.

Secondary Outcome Measures :
  1. Remission Duration/Time to Progression (TTP) [ Time Frame: 6 months to disease progression, period covered up to 12 years following treatment; Data cutoff for analysis was October 2014. ]
    TTP was defined as time from initiation of treatment to primary refractory disease or CLL progression. TTP was censored for therapy-related myelodysplastic syndrome (t-MDS) or acute myelogenous leukemia (t-AML) and death in remission. TTP calculated using Kaplan-Meier estimates.

  2. Overall Survival (OS) Rate [ Time Frame: 6 months to disease progression, period covered up to 12 years following treatment; Data cutoff for analysis was October 2014. ]
    OS was defined as the time from the initiation of treatment to last follow-up date or death. OS were calculated using Kaplan-Meier estimates.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00794820

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United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Genentech, Inc.
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Principal Investigator: Susan O'Brien, M.D. M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00794820     History of Changes
Other Study ID Numbers: 2003-0591
NCI-2010-01220 ( Registry Identifier: NCI CTRP )
First Posted: November 20, 2008    Key Record Dates
Results First Posted: August 23, 2016
Last Update Posted: May 8, 2018
Last Verified: April 2018
Keywords provided by M.D. Anderson Cancer Center:
Chronic Lymphocytic Leukemia
Fludarabine phosphate
Additional relevant MeSH terms:
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Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Fludarabine phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Antimetabolites, Antineoplastic
Antiviral Agents
Anti-Infective Agents