CFAR Study in Patients With Chronic Lymphocytic Leukemia

NCT00525603 | Completed Phase 2 Results

• 1 other identifier: 2005-0269
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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. 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. 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. 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.

Conditions

Leukemia; Chronic Lymphocytic Leukemia

Keywords

Chronic Lymphocytic Leukemia; CML; Leukemia; Cyclophosphamide; Fludarabine; Alemtuzumab; Rituximab; CFAR

Outcome Measures

Primary Outcomes (1)

• Overall Participant Response

  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.

  Evaluated after 3 courses of 4 week therapy (12 weeks)

Study Arms (1)

CFAR

EXPERIMENTAL

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; Drug: Fludarabine; Drug: Alemtuzumab; Drug: Rituximab

Interventions

Cyclophosphamide DRUG

200 mg/m\^2/day 3-5 IV 5-30 minutes

Also known as: Cytoxan®, Neosar®

CFAR

Fludarabine DRUG

20 mg/m\^2/day 3-5 IV 5-30 minutes

Also known as: Fludara®, Fludarabine Phosphate

CFAR

Alemtuzumab DRUG

30 mg Days 1, 3, 5 IV 2-4 hours

Also known as: Campath, Campath-1H

CFAR

Rituximab DRUG

375 mg/m\^2/day 2 IV 4-6 hours

Also known as: Rituxan®

CFAR

Eligibility Criteria

• Age: Up to 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Patients older than 70 years.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bayer: collaborator

Study Sites (1)

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M.D. Anderson's internet site

MeSH Terms

Conditions

Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; Alemtuzumab; Rituximab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived

Results Point of Contact

• Title: William G. Wierda, MD/Associate Professor
• Organization: The University of MD Anderson Cancer Center

eharriso@mdanderson.org

713-745-0428

Study Officials

• William G. Wierda, M.D., Ph.D.

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2007
• First Posted: September 6, 2007
• Study Start: June 1, 2005
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: March 4, 2013
• Results First Posted: March 4, 2013

Record last verified: 2013-01

Locations

US (1)