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

Study Description

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

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 or disease	Intervention/treatment	Phase
Chronic Lymphocytic Leukemia	Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Alemtuzumab; Drug: Rituximab	Phase 2

  Show Detailed Description

Study Design

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	80 participants
Intervention Model:	Single Group Assignment
Masking:	None (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)
Study Start Date :	December 2002
Actual Primary Completion Date :	January 2011
Actual Study Completion Date :	January 2011

Arms and Interventions

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm

Intervention/treatment

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

Outcome Measures

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Number of Participants With an Overall Response [ Time Frame: 6 cycles of treatment (28 days per cycle) ]
   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.

Eligibility Criteria

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	Child, Adult, Senior
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. 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.
2. All patient must have been previously treated with chemotherapy.
3. 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.
4. All patients must have a Zubrod performance status of 0-3.
5. 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.
6. 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).
7. Patients must not have untreated or uncontrolled life-threatening infection.
8. Patients must sign informed consent.

Exclusion Criteria:

1. None

Contacts and Locations

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

UT MD Anderson Cancer Center 

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT01082939 History of Changes
Other Study ID Numbers:	DM02-593
First Posted:	March 9, 2010
Results First Posted:	October 21, 2011
Last Update Posted:	February 20, 2012
Last Verified:	February 2012

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