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

NCT00003659 | Completed Phase 2 Results

• 3 other identifiers: 98-080MSKCC-98080NCI-G98-1483
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Leukemia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  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 Outcomes (2)

• Utilize Flow Cytometry and Polymerase Chain Reaction as Sensitive Measures of Minimal Residual Disease

  3 years

• Overall Survival Status

  up to 5 years

Study Arms (1)

intermediate or high risk chronic lymphocytic leukemia

EXPERIMENTAL

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; Biological: rituximab; Drug: cyclophosphamide; Drug: fludarabine phosphate

Interventions

filgrastim BIOLOGICAL

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.

intermediate or high risk chronic lymphocytic leukemia

rituximab BIOLOGICAL

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.

intermediate or high risk chronic lymphocytic leukemia

cyclophosphamide DRUG

Cyclophosphamide 3000mg/m2 will be given intravenously q 2 - 3 weeks x 3 doses.

intermediate or high risk chronic lymphocytic leukemia

fludarabine phosphate DRUG

Fludarabine will be administered intravenously at a dose of 25 mg/m2 per day x 5 days every 4 weeks.

intermediate or high risk chronic lymphocytic leukemia

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Filgrastim; Rituximab; Cyclophosphamide; fludarabine phosphate

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Dr. David Scheinberg
• Organization: Memorial-Sloan Kettering Cancer Center

scheinbd@mskcc.org

646-888-2190

Study Officials

• Mark Adam Weiss, MD

  Memorial Sloan Kettering Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: January 27, 2003
• Study Start: September 1, 1998
• Primary Completion: May 1, 2009
• Study Completion: May 1, 2009
• Last Updated: October 24, 2017
• Results First Posted: December 31, 2012

Record last verified: 2017-09

Locations

US (1)