CFAR Study in Patients With Chronic Lymphocytic Leukemia

This study has been completed.
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00525603
First received: September 4, 2007
Last updated: January 25, 2013
Last verified: January 2013
  Purpose

Primary Objective:

1. Evaluate the ability of Cyclophosphamide, Fludarabine, Alemtuzumab, and Rituximab (CFAR) to increase the proportion of patients with <5% CD5/CD19+ cells in bone marrow to 66% following 3 courses of treatment without significantly increasing the incidence of pneumonia or sepsis compared to a historic group of patients treated with the combination fludarabine, cyclophosphamide, and rituximab (FCR).

Second Objectives:

  1. Assess complete remission (CR), nodular partial remission (nPR), and partial remission (PR) rates (overall response) in high-risk, previously untreated patients with CLL treated with CFAR.
  2. Evaluate molecular remission in bone marrow by polymerase chain reaction (PCR) for the clonal immunoglobulin heavy chain variable gene in responders treated with CFAR.
  3. Assess immune parameters including blood T cell counts and subset distribution and serum immunoglobulin levels pretreatment, during treatment, and post-treatment in patients treated with CFAR.

Condition Intervention Phase
Leukemia
Chronic Lymphocytic Leukemia
Drug: Cyclophosphamide
Drug: Fludarabine
Drug: Alemtuzumab
Drug: Rituximab
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 Cyclophosphamide, Fludarabine, Alemtuzumab, and Rituximab (CFAR) in High-Risk Previously Untreated Patients With CLL

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Overall Participant Response [ Time Frame: Evaluated after 3 courses of 4 week therapy (12 weeks) ] [ Designated as safety issue: No ]
    Overall Response: Complete remission (CR), nodular partial remission (nPR), and partial remission (PR) rates (overall response) in high-risk, previously untreated patients with CLL treated with CFAR. National Cancer Institute - Working Group (NCI-WG) response criteria. CR defined as zero nodes, Liver/spleen not palpable, zero symptoms, polymorphonuclear leukocyte (PMN)>1,500/uL, Platelets >100,000uL, Hemoglobin (untransfused) >11.0g/dL, Lymphocytes <4,000/uL and Bone Marrow Aspirate biopsy <30% lymphocytes with no lymphocyte infiltrate; PR defined as nodes >/= 50% decrease,Liver/spleen >/= 50% decrease, symptoms not applicable, PMN >1,500/uL or >50% improvement from baseline, Platelets 100,000uL or >/=50% decrease improvement from baseline, Hemoglobin (untransfused) >11.0g/dL or >50% improvement from baseline, Lymphocytes >50% decrease and Bone Marrow Aspirate biopsy Not Applicable for PR; with nPR defined same as PR but with <30% lymphocytes with residual disease on biopsy.


Enrollment: 60
Study Start Date: June 2005
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CFAR
CFAR = Cyclophosphamide 200 mg/m^2/day 3-5 intravenous (IV) 5-30 minutes, Fludarabine 20 mg/m^2/day 3-5 IV 5-30 minutes, Alemtuzumab 30 mg 1, 3,5 IV 2-4 hours, and Rituximab 375 mg/m^2/day 2 IV 4-6 hours
Drug: Cyclophosphamide
200 mg/m^2/day 3-5 IV 5-30 minutes
Other Names:
  • Cytoxan®
  • Neosar®
Drug: Fludarabine
20 mg/m^2/day 3-5 IV 5-30 minutes
Other Names:
  • Fludara®
  • Fludarabine Phosphate
Drug: Alemtuzumab
30 mg Days 1, 3, 5 IV 2-4 hours
Other Names:
  • Campath
  • Campath-1H
Drug: Rituximab
375 mg/m^2/day 2 IV 4-6 hours
Other Name: Rituxan®

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All patients must have a diagnosis of CLL by immunophenotyping and flow cytometry analysis of blood or bone marrow and be previously untreated.
  • All patients must be younger than 70 years and have a serum beta-2 microglobulin of >/= 4.0mg/L.
  • All patients with Rai stage III-IV are eligible for treatment on this protocol. - OR - All patients with Rai stage 0-II who meet one or more indication for treatment as defined by the NCI-sponsored Working Group are eligible for treatment on this protocol.
  • All patients must have a Zubrod performance status of 0-3.
  • All patients must have adequate renal and hepatic function (serum creatinine </= 2mg/dL; total bilirubin </= 2.5mg/dL). Patients with renal or liver dysfunction due to organ infiltration by lymphocytes may be eligible after discussion with the Principle Investigator and appropriate dose adjustment considered.
  • Patients may not receive concurrent chemotherapy, radiotherapy, or immunotherapy. Localized radiotherapy to an area not compromising bone marrow function does not apply, nor do hematopoietic growth factors such as erythropoietin, Granulocyte colony-stimulating factor (G-CSF), Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF), etc.
  • Patients must not have untreated or uncontrolled life-threatening infection.
  • Patients must sign informed consent.

Exclusion Criteria:

Patients older than 70 years.

  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: NCT00525603

Locations
United States, Texas
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Bayer
Investigators
Principal Investigator: William G. Wierda, M.D., Ph.D. M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00525603     History of Changes
Other Study ID Numbers: 2005-0269
Study First Received: September 4, 2007
Results First Received: October 4, 2012
Last Updated: January 25, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Chronic Lymphocytic Leukemia
CML
Leukemia
Cyclophosphamide
Fludarabine
Alemtuzumab
Rituximab
CFAR

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

ClinicalTrials.gov processed this record on October 23, 2014