Fludarabine, Rituximab, and Alemtuzumab for B-Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

NCT ID: NCT00143065

Last Updated: 2017-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-08-31
• Study Completion Date: 2009-07-31

Brief Summary

This purpose of this study is to assess the toxicity and the rate of complete and overall response using fludarabine, rituximab, and alemtuzumab to treat patients with B-chronic lymphocytic leukemia or small lymphocytic leukemia who have received previous treatment.

Detailed Description

Immunotherapy, or treatments that work by boosting immune function in the body, such as monoclonal antibodies have shown some efficacy against different types of leukemia. Researchers have learned to manufacture antibodies outside of the human body that can bind to specific targets in cancer cells. Monoclonal antibodies are designed to recognize different proteins on specific cancer cells. The current study combines two monoclonal antibodies, rituximab and fludarabine. Rituximab attaches to a protein called the CD20 antigen that is found almost exclusively on the surface of B-cells with leukemia. Once rituximab attaches to the protein, the immune system activates to kill the malignant B-cells. Alemtuzumab works in a similar way by attaching with the CD25 antigen and also has activity in patients with p53 gene mutations. Previous studies indicate that both rituximab and alemtuzumab separately have some efficacy against lymphocytic leukemia. Research has also shown that fludarabine works against the disease. Rituximab and fludarabine in combination appear to have a high response rate in patients. Researchers are seeking to improve efficacy data by adding alemtuzumab to the combination of rituximab and fludarabine in this study.

This study will evaluate the safety and efficacy of fludarabine, rituximab, and alemtuzumab in patients with previously treated B-cell lymphocytic leukemia and small lymphocytic leukemia. Blood and bone marrow tests will assess genetic features associated with response to therapy, immune recovery, mechanisms of alemtuzumab's signaling, routes of drug resistance, and traces of residual disease following complete response in patients.

Patients in this study will receive fludarabine, rituximab, and alemtuzumab. These drugs will be administered through intravenous infusions. The treatment period will last 22 weeks. Fludarabine will not be given during week one, 5 days during week 2, and 5 days during weeks 6, 10, 14, 18, and 22. Rituximab will not be given during week one, 3 times the second week, and day one of weeks 6, 10, 14, 18, and 22. Alemtuzumab will be given 3 times during week one, once during week 2, and day 2 of weeks 6, 10, 14, 18, and 22. The dosage amount of rituximab and alemtuzumab will be increased depending upon the degree of side effects. Several tests and exams will be given throughout the study to closely monitor patients. Treatments will be discontinued due to disease growth or unacceptable side effects.

Conditions

Lymphoma, Small Lymphocytic; Lymphocytic Leukemia, Chronic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Fludarabine

25 mg/m2/day for 5 days every 28 days (Week 2,6,10,14, 18,and 22) will be administered by IV over 10-30 minutes. (Fludarabine should be given AFTER rituximab on all days on which both drugs will be administered.)

Intervention Type: DRUG

Rituximab

Day 1, week 2 of cycle 1 rituximab 100 mg will be administered by IV, without dose escalation, over 4 hours (rate: 25 mg/hr). Day 3, week 2 of cycle 1 rituximab 375 mg/m2 will be administered by IV. Rituximab can be administered at 50 mg/hr. If hypersensitivity or infusion related events do not occur, the infusion rate will be escalated in 50 mg/hr increments every 30 minutes to a maximum of 400 mg/hr.

• On Day 5, week 2 of cycle 1 rituximab 375 mg/m2 will be administered by IV. Rituximab can be administered at 100 mg/hr. If hypersensitivity or infusion related events do not occur, the infusion rate will be escalated in 100 mg/hr increments every 30 minutes to a maximum of 400 mg/hr.
• Rituximab 375 mg/m2 will be repeated on Day 1 of Week 6, 10, 14, 18, and 22. During these treatments, acetaminophen and diphenhydramine prophylactic treatment is left to the discretion of the treating physician.

Intervention Type: DRUG

Alemtuzumab

The dose of alemtuzumab will be escalated during Week 1 of therapy. On Day 1 of Week 1, a dose of 3 mg should be administered IV over 2-hours. If this dose is well tolerated(grade 2 or less infusion or skin related toxicity), then the dose on Day 2 can be increased to 10 mg IV over 2 hours. If this dose is well tolerated, then the dose on Day 3 will be increased to 30 mg IV over 2-hours, and if tolerated, then day 5 and all subsequent alemtuzumab doses will be 30 mg. Vital signs (blood pressure, pulse, respiration rate,temperature, and O2 saturation) and skin assessment should be assessed at baseline, 1-hour, and 1-hour post administration during week 1 and 2. Following successful escalation to 30 mg of alemtuzumab, all subsequent doses of alemtuzumab will be 30 mg administered on the second day of fludarabine therapy (week 2,6,10,14,18,and 22).

Intervention Type: DRUG

Other Intervention Names

Fludara; Rituxan; Campath

Eligibility Criteria

Inclusion Criteria

• Must have B-CLL/SLL
• active disease
• >=1 prior systemic therapy
• ECOG PS 0-2.

Exclusion Criteria

• Pregnant or nursing women

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ohio State University Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

John Byrd

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

John C. Byrd, M.D.

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

Ohio State University

Columbus, Ohio, United States

Countries

United States

Related Links

http://cancer.osu.edu/.

Jamesline

Other Identifiers

OSU-0404

Identifier Type: -

Identifier Source: org_study_id