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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00143065
First received: August 31, 2005
Last updated: October 20, 2011
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Lymphoma, Small Lymphocytic
Lymphocytic Leukemia, Chronic
Drug: Fludarabine
Drug: Rituximab
Drug: Alemtuzumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Feasibility/Phase II Trial of Fludarabine, Rituximab, and Alemtuzumab for Previously Treated B-Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)

Resource links provided by NLM:


Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • Assess the rate of complete (CR) and overall response (ORR) using fludarabine, rituximab, and alemtuzumab [ Time Frame: 2005-present ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Assess toxicity of this regimen. [ Time Frame: 2005-present ] [ Designated as safety issue: Yes ]

Enrollment: 8
Study Start Date: August 2005
Study Completion Date: July 2009
Primary Completion Date: February 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: 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.)
    Other Name: Fludara
    Drug: Rituximab
    • On 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).
    • On 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.
    Other Name: Rituxan
    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).
    Other Name: Campath
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • Pregnant or nursing women
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00143065

Locations
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Ohio State University Comprehensive Cancer Center
Investigators
Principal Investigator: John C. Byrd, M.D. Ohio State University
  More Information

Additional Information:
No publications provided

Responsible Party: Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00143065     History of Changes
Other Study ID Numbers: OSU-0404
Study First Received: August 31, 2005
Last Updated: October 20, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Ohio State University Comprehensive Cancer Center:
Antigens, CD5
Antigens, CD19
Antigens, CD20

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Rituximab
Alemtuzumab
Fludarabine
Fludarabine phosphate
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents

ClinicalTrials.gov processed this record on October 19, 2014