Fludarabine, Cyclophosphamide, and Rituximab - High Dose Frontline

April 5, 2018 updated by: M.D. Anderson Cancer Center

Fludarabine, Cyclophosphamide, and Multiple Dose Rituximab as Frontline Therapy in Chronic Lymphocytic Leukemia (CLL)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle.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

Study Type

Interventional

Enrollment (Actual)

66

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • Rituxan®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
6 months to disease progression, period covered up to 12 years following treatment; Data cutoff for analysis was October 2014.
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.
6 months to disease progression, period covered up to 12 years following treatment; Data cutoff for analysis was October 2014.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Collaborators

Genentech, Inc.

Investigators

  • Principal Investigator: Susan O'Brien, M.D., M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2003

Primary Completion (Actual)

December 1, 2014

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

November 18, 2008

First Submitted That Met QC Criteria

November 18, 2008

First Posted (Estimate)

November 20, 2008

Study Record Updates

Last Update Posted (Actual)

May 8, 2018

Last Update Submitted That Met QC Criteria

April 5, 2018

Last Verified

April 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2003-0591 (OTHER: University of Michigan IRBMED)
  • NCI-2010-01220 (Registry Identifier: NCI CTRP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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