Cyclophosphamide, Fludarabine, Alemtuzumab, and Rituximab (CFAR) for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Collaborator:	Bayer
Information provided by (Responsible Party):	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT01082939

Purpose

The goal of this clinical research study is to learn if the combination of fludarabine, cyclophosphamide, alemtuzumab, and rituximab is effective in treating chronic lymphocytic leukemia in patients who have already been treated with chemotherapy.

Primary Objectives:

Evaluate the therapeutic efficacy, including the complete remission (CR), nodular partial remission (NPR), and partial remission (PR) rates (overall response) of combined cyclophosphamide, fludarabine, alemtuzumab, and rituximab (CFAR) in previously treated patients with Chronic Lymphocytic Leukemia (CLL).

Second Objectives:

Assess the toxicity profile of CFAR in previously treated patients with CLL.
Monitor for infection and determine incidence and etiology of infection including cytomegalovirus in patients treated with CFAR.
Evaluate molecular remission by polymerase chain reaction (PCR) for the clonal immunoglobulin heavy chain variable gene in responding patients treated with CFAR.
Assess immune parameters, including pretreatment, during treatment, and post-treatment blood T-cell counts and subset distribution and serum immunoglobulin levels in patients treated with CFAR.

Condition	Intervention	Phase
Chronic Lymphocytic Leukemia	Drug: Fludarabine Drug: Cyclophosphamide Drug: Alemtuzumab Drug: Rituximab	Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: 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 Previously Treated Patients With Chronic Lymphocytic Leukemia (CLL)

Resource links provided by NLM:

MedlinePlus related topics: Acute Lymphocytic Leukemia Cancer Chronic Lymphocytic Leukemia Leukemia

Drug Information available for: Cyclophosphamide Fludarabine Fludarabine phosphate Rituximab Alemtuzumab

U.S. FDA Resources

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

Primary Outcome Measures:

Number of Participants With an Overall Response [ Time Frame: 6 cycles of treatment (28 days per cycle) ] [ Designated as safety issue: No ]
Overall (OR) is the total number of participants with any response: Complete remission (CR), is defined as > 30% lymphocytes in the bone marrow, recovery of blood counts and no clinical symptoms; Nodular partial remission (NPR), is the same as CR but with nodules; Partial remission (PR) is > 50% decrease of clinical symptoms from baseline and recovery from blood counts.

Enrollment:	80
Study Start Date:	December 2002
Study Completion Date:	January 2011
Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: CFAR CFAR: Cyclophosphamide 250 mg/m^2/day intravenous (IV) Days 3-5, Fludarabine 25 mg/m^2/day IV Days 3-5, Alemtuzumab 30 mg IV Days 1, 3 and 5 over 2-4 hours, repeated every four weeks for a total of 6 planned cycles, and Rituximab Cycle 1 (Week 1): 375 mg/m^2/day IV Day 2 over 4- 6 hours, Cycle 2 - 6 (Week 1): 500 mg/m^2/day IV Day 2 over 4- 6 hours.	Drug: Fludarabine 25 mg/m^2/day IV on Days 3-5; repeated every four weeks for a total of 6 planned cycles. Other Names: Fludara Fludarabine Phosphate Drug: Cyclophosphamide 250 mg/m^2/day IV on Days 3-5; repeated every four weeks for a total of 6 planned cycles. Other Names: Cytoxan Neosar Drug: Alemtuzumab 30 mg IV on Days 1, 3 and 5 over 2-4 hours; repeated every four weeks for a total of 6 planned cycles. Other Names: Campath-1h Campath Drug: Rituximab Cycle 1 (Week 1): 375 mg/m^2/day IV on Day 2 over 4- 6 hours Cycle 2 - 6 (Week 1): 500 mg/m^2/day IV on Day 2 over 4- 6 hours Other Name: Rituxan

Arms

Assigned Interventions

Experimental: CFAR

CFAR: Cyclophosphamide 250 mg/m^2/day intravenous (IV) Days 3-5, Fludarabine 25 mg/m^2/day IV Days 3-5, Alemtuzumab 30 mg IV Days 1, 3 and 5 over 2-4 hours, repeated every four weeks for a total of 6 planned cycles, and Rituximab Cycle 1 (Week 1): 375 mg/m^2/day IV Day 2 over 4- 6 hours, Cycle 2 - 6 (Week 1): 500 mg/m^2/day IV Day 2 over 4- 6 hours.

Drug: Fludarabine

25 mg/m^2/day IV on Days 3-5; repeated every four weeks for a total of 6 planned cycles.

Other Names:

Fludara
Fludarabine Phosphate

Drug: Cyclophosphamide

250 mg/m^2/day IV on Days 3-5; repeated every four weeks for a total of 6 planned cycles.

Other Names:

Cytoxan
Neosar

Drug: Alemtuzumab

30 mg IV on Days 1, 3 and 5 over 2-4 hours; repeated every four weeks for a total of 6 planned cycles.

Other Names:

Campath-1h
Campath

Drug: Rituximab

Cycle 1 (Week 1): 375 mg/m^2/day IV on Day 2 over 4- 6 hours

Cycle 2 - 6 (Week 1): 500 mg/m^2/day IV on Day 2 over 4- 6 hours

Other Name: Rituxan

Show Detailed Description

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

All patients must have been diagnosed with CLL by immunophenotyping and flow cytometry analysis of blood or bone marrow demonstrating a monoclonal population of CD5 and CD19 positive cells.
All patient must have been previously treated with chemotherapy.
All patients with Rai stage III-IV are eligible for treatment with 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 with 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 or GCSF, GM-CSF etc).
Patients must not have untreated or uncontrolled life-threatening infection.
Patients must sign informed consent.

Exclusion Criteria:

1. None

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01082939

Locations

United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Bayer

Investigators

Study Chair:

William G. Wierda, MD, PhD, BS

UT MD Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT01082939 History of Changes
Other Study ID Numbers:	DM02-593
Study First Received:	March 5, 2010
Results First Received:	July 26, 2011
Last Updated:	February 17, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

Chronic lymphocytic leukemia
Refractory CLL
CFAR
Alemtuzumab
Campath-1H
Campath
Cyclophosphamide
Cytoxan

Neosar
Fludarabine
Fludara
Fludarabine Phosphate
Rituximab
Rituxan
CLL

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
Campath 1G
Rituximab
Fludarabine

Alemtuzumab
Antibodies, Neoplasm
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

ClinicalTrials.gov processed this record on May 23, 2012