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

NCT01082939 | Completed Phase 2 Results

• 1 other identifier: DM02-593
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Lymphocytic Leukemia

Keywords

Chronic lymphocytic leukemia; Refractory CLL; CFAR; Alemtuzumab; Campath-1H; Campath; Cyclophosphamide; Cytoxan; Neosar; Fludarabine; Fludara; Fludarabine Phosphate; Rituximab; Rituxan; CLL

Outcome Measures

Primary Outcomes (1)

• Number of Participants With an Overall Response

  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.

  6 cycles of treatment (28 days per cycle)

Study Arms (1)

CFAR

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Alemtuzumab; Drug: Rituximab

Interventions

Fludarabine DRUG

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

Also known as: Fludara, Fludarabine Phosphate

CFAR

Cyclophosphamide DRUG

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

Also known as: Cytoxan, Neosar

CFAR

Alemtuzumab DRUG

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

Also known as: Campath-1h, Campath

CFAR

Rituximab DRUG

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

Also known as: Rituxan

CFAR

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• \. None

Sponsors & Collaborators

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

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

fludarabine; fludarabine phosphate; Cyclophosphamide; Alemtuzumab; Rituximab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; 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, PhD, BS / Associate Professor
• Organization: The University of Texas MD Anderson Cancer Center

eharriso@mdanderson.org

713-745-0428

Study Officials

• William G. Wierda, MD, PhD, BS

  UT MD Anderson Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

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: March 5, 2010
• First Posted: March 9, 2010
• Study Start: December 1, 2002
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: February 20, 2012
• Results First Posted: October 21, 2011

Record last verified: 2012-02

Locations

US (1)