Fludarabine, Cyclophosphamide, and Rituximab in Treating Patients Who Have Chronic Lymphocytic Leukemia

September 22, 2017 updated by: Memorial Sloan Kettering Cancer Center

A Phase II Study of Fludarabine Induction With Sequential High Dose Cyclophosphamide and Rituximab as Consolidation Therapy for Previously Untreated Patients With Intermediate and High-Risk Chronic Lymphocytic Leukemia

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells.

PURPOSE: Phase II trial to study the effectiveness of fludarabine plus high-dose cyclophosphamide and rituximab in treating patients who have previously untreated chronic lymphocytic leukemia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the response rate in patients with chronic lymphocytic leukemia treated with sequential fludarabine, high dose cyclophosphamide, and rituximab.
  • Survival up to 5 years
  • Utilize flow cytometry and polymerase chain reaction as sensitive measures of minimal residual disease in these patients.

OUTLINE: This is an open label study.

Patients receive fludarabine IV once daily for 5 days. Treatment is repeated every 4 weeks for 3 or 6 courses.

Three weeks later, cyclophosphamide is administered intravenously every 2-3 weeks for 3 courses. Filgrastim (G-CSF) is administered on days 2-10. Beginning 4 weeks after the last dose of cyclophosphamide, patients receive rituximab by intravenous infusion once weekly for 4 weeks.

Patient are followed every 3 months until death.

PROJECTED ACCRUAL: This study will accrue 30 patients within 3 years.

Study Type

Interventional

Enrollment (Actual)

39

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
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering 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

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • Patients must have either intermediate or high-risk chronic lymphocytic leukemia as defined by the three-stage Rai system (see section 2.2 page 2). Patients with Rai intermediate risk disease should meet the criteria for active disease as outlined by the NCI Working Group guidelines (including weight loss, fatigue, fevers, evidence of progressive marrow failure, splenomegaly, progressive lymphadenopathy, or progressive lymphocytosis with a rapid doubling time).
  • Patients must be previously untreated (with cytoreductive agents) for their CLL.
  • The patient must have an absolute lymphocytosis in the blood of at least 5,000 lymphocytes/μl, or bone marrow lymphocytosis greater than or equal to 30% of all nucleated cells. These lymphocytes must have an appropriate immunophenotype for CLL including expression of CD5 and CD20.
  • Karnofsky performance status equal to or greater than 60% (see Appendix B).
  • Eligible patients should have a reasonable life-expectancy greater than four weeks.
  • Age ≥ 18 years and ≤ 75 years.
  • Total bilirubin ≤ 2.0 mg per deciliter. Total creatinine ≤ 2.0 mg/ dl.
  • Platelet count ≥ 50,000/ ul.
  • Signed informed consent, which indicates the investigational nature of this, is required.
  • No patient may be entered onto the study without consultation with the principal investigator.

EXCLUSION CRITERIA:

  • Patients with Rai intermediate risk disease who meet the criteria of Montserrat "smouldering leukemia" will not be eligible for treatment on this protocol.
  • Patients with significant autoimmune hemolytic anemia or autoimmune thrombocytopenia shall not be eligible for treatment on this protocol as there is some evidence that fludarabine can worsen these conditions.
  • Patients with active infections requiring systemic antibiotics.
  • Prior cytotoxic treatment of their CLL.
  • Pregnant or lactating women. Women and men of childbearing age should use effective contraception.
  • Patients with a serious cardiac condition.
  • Concomitant chemotherapy or radiotherapy while on protocol.
  • Concomitant prednisone therapy will not be permitted as the combination of fludarabine and prednisone is known to increase the risk of opportunistic infections. Patients may receive intravenous immunoglobulin (IVIG) and other supportive care measures as clinically appropriate while on protocol.

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: intermediate or high risk chronic lymphocytic leukemia
This is a single-arm open-label pilot study designed to assess the antileukemic activity of a regimen containing sequential administration of fludarabine, high-dose cyclophosphamide, and rituximab.
Biological: filgrastim
Filgrastim (300 μg for patients ≤ 70 kg or 480 μg for patients > 70 kg) will be administered beginning two days after each cyclophosphamide dose and given for a total of eight subcutaneous daily doses.
Biological: rituximab
Approximately four weeks after the completion of the last cyclophosphamide dose, patients will receive rituximab 375mg/m2 as an intravenous infusion once weekly for four doses.
Drug: cyclophosphamide
Cyclophosphamide 3000mg/m2 will be given intravenously q 2 - 3 weeks x 3 doses.
Drug: fludarabine phosphate
Fludarabine will be administered intravenously at a dose of 25 mg/m2 per day x 5 days every 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate
Time Frame: 3 years
Response was determined as indicated in the protocol. The categories are: complete response, nodular partial response, partial response and failure. The major criteria for determination of response to therapy in patients with CLL include physical examination and examination of the peripheral blood and bone marrow. The laboratory and radiographic studies which were abnormal pre-study, will be repeated to document the degree of maximal response.
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Utilize Flow Cytometry and Polymerase Chain Reaction as Sensitive Measures of Minimal Residual Disease
Time Frame: 3 years
The flow cytometric response and the molecular polymerase chain reaction (PCR) response was captured as indicated in the protocol. Immunophenotypic analysis of bone marrow and/ or peripheral blood demonstrate a normal k:λ ratio and a normal number of CD5/CD19 (or CD5/CD20) dual staining cells (<5% of the lymphocyte gate).
3 years
Overall Survival Status
Time Frame: up to 5 years
The 5 year survival rate. The survival of patients with this disease is dependent on the stage of disease. Two useful staging systems are: Three-stage Rai System Clinical Feature and the Binet System.
up to 5 years

Collaborators and Investigators

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

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI)

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

September 1, 1998

Primary Completion (ACTUAL)

May 1, 2009

Study Completion (ACTUAL)

May 1, 2009

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

January 26, 2003

First Posted (ESTIMATE)

January 27, 2003

Study Record Updates

Last Update Posted (ACTUAL)

October 24, 2017

Last Update Submitted That Met QC Criteria

September 22, 2017

Last Verified

September 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 98-080
  • MSKCC-98080
  • NCI-G98-1483

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.

Clinical Trials on Leukemia

Clinical Trials on filgrastim

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Jordan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe