Fludarabine, Cyclophosphamide, and Rituximab in Treating Patients Who Have Chronic Lymphocytic Leukemia - Full Text View

Purpose

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.

Condition	Intervention	Phase
Leukemia	Biological: filgrastim Biological: rituximab Drug: cyclophosphamide Drug: fludarabine phosphate	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:	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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Chronic Lymphocytic Leukemia Leukemia

Drug Information available for: Cyclophosphamide Fludarabine Fludarabine phosphate Filgrastim Lenograstim Granulocyte colony-stimulating factor Rituximab

U.S. FDA Resources

Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:

Overall Response Rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Response was determined as inicated in the protocol. The catergories are: complete response, nodular partial response, partial response and failure.

Secondary Outcome Measures:

Utilize Flow Cytometry and Polymerase Chain Reaction as Sensitive Measures of Minimal Residual Disease [ Time Frame: 3 years ] [ Designated as safety issue: No ]
The flow cytometric response and the molecular polymerase chain reaction (PCR) response was captured as indicated in the protocol.
Overall Survival Status [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
The 5 year survival rate

Enrollment:	39
Study Start Date:	September 1998
Study Completion Date:	May 2009
Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Arms

Assigned Interventions

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.

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.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003659

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Mark Adam Weiss, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00003659 History of Changes
Other Study ID Numbers:	98-080, MSKCC-98080, NCI-G98-1483
Study First Received:	November 1, 1999
Results First Received:	November 28, 2012
Last Updated:	November 28, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:

stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia

Additional relevant MeSH terms:

Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Fludarabine monophosphate
Rituximab
Fludarabine
Lenograstim

Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents

ClinicalTrials.gov processed this record on May 16, 2013