Phase 2 Fludarabine, Cytoxan and FCCAM <Alemtuzumab> in Untreated B-Cell Chronic Lymphocytic Leukemia

Leukemia Clinical Trial

Official title:

A Multi-Center Phase 2 Efficacy and Pharmacokinetic Study Evaluating Fludarabine, Cyclophosphamide, and Subcutaneous Campath (FCCam, Alemtuzumab) for Previously Untreated B-Cell Chronic Lymphocytic Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00230282
• Other study ID #: IRB-13053
• Secondary ID: 3118580071HEMCLL
• Status: Completed
• Phase: Phase 2
• First received: September 28, 2005
• Last updated: September 25, 2014
• Start date: July 2004
• Est. completion date: October 2011

Study information

• Verified date: September 2014
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study was to evaluate the safety and efficacy of the combination of fludarabine and cyclophosphamide in previously untreated CLL patients. Participants will receive fludarabine and cyclophosphamide on days 1, 2, and 3 of six 28-day cycles.

Description:

This single-arm study evaluated the safety and efficacy of the combination of fludarabine 25 mg/m2/d IV and cyclophosphamide 250 mg/m2/d SC in previously untreated CLL patients. Participants received fludarabine and cyclophosphamide on days 1, 2, and 3 of six 28-day cycles, followed by a no-treatment rest period (observation) for 3 to 12 weeks.

Responders entered a no-treatment rest period (observation) for 3 to 8 weeks, then depending on status, continued on follow-up or on-study to receive Campath stating at 3 mg/day with the dose adjusted to the maximum tolerated dose.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: October 2011
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• = age 18

• Karnofsky performance status 60% or above

• Confirmed immunohistological diagnosis of Chronic Lymphocytic Leukemia (CLL)

• Rai Stage I to IV as follows:

• Advanced stage disease (Rai Stage III or IV, or modified Rai High Risk)

• OR

• Patients with Rai Stage I - II or (Modified Rai Intermediate-Risk) disease must have an indication for therapy based on 1996 NCI revised criteria for active disease as follows:

• Any one of the following disease-related symptoms:

1. Weight loss = 10% body weight within the previous 6 months

2. Extreme fatigue

3. Fever greater than 100.5° F for = 2 weeks without evidence of infection

4. Night sweats without evidence of infection

• Evidence of progressive marrow failure based on the development of worsening of anemia or thrombocytopenia

• Autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroid therapy

• Massive (> 6 cm below the left costal margin) or progressive splenomegaly

• Bulky (>10 cm in cluster) or progressive lymphadenopathy

• Progressive lymphocytosis > 50% increase over 2 months, or anticipated doubling time < 6 months

• Patients with immunoglobulin VH gene in unmutated nucleotide sequence configuration, as defined by = 98% homology with the nearest germline counterpart

• Serum creatinine = 2x the upper limit of normal

• Total serum bilirubin = 2x the upper limit of normal.

• AST = 2x the upper limit of normal.

• ALT = 2x the upper limit of normal.

• Signed written informed consent

Exclusion Criteria:

• Prior pharmacological treatment for CLL

• Past history of anaphylaxis following exposure to monoclonal antibodies

• Active secondary malignancy or a history of malignant disease (other than CLL or non-melanoma skin cancer) within the preceding 5 years

• Any medical condition requiring systemic corticosteroids

• Active systemic infection

• Major systemic or other illness (including Coombs positivity and active hemolysis) that would, in the opinion of the investigator, interfere with the patient's ability to comply with the protocol, compromise patient safety, or interfere with the interpretation of study results

• HIV positive by serologic testing

• Pregnant or nursing female

• Unwilling/unable to practice an acceptable form of contraception.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• B-cell Leukemia
• Chronic Leukemia
• Chronic Lymphocytic Leukemia (CLL)
• Leukemia
• Leukemia, B-Cell
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• Alemtuzumab
3 to 30 mg, IV
• Fludarabine
[(2R,3R,4S,5R)-5-(6-amino-2-fluoro-purin-9-yl)- 3,4-dihydroxy-oxolan-2-yl]methoxyphosphonic acid
• Cytoxan
(RS)-N,N-bis(2-chloroethyl)-1,3,2-oxazaphosphinan-2-amine 2-oxide

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Steven E. Coutre	Bayer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects Maintaining Partial Response (PR) or Complete Response (CR)	Response criteria as per the NCI-WG Revised Guidelines for B-CLL; Complete remission: No lymphadenopathy by physical exam No hepatomegaly or splenomegaly Absence of constitutional symptoms Polymorphonuclear leukocytes > 1,500/uL, Platelets > 100,000/uL, Hemoglobin > 11.0 g/dL Bone marrow aspirate and biopsy normocellular with < 30% lymphocytes Absent lymphoid nodules; Partial remission: 50% decrease in peripheral blood lymphocyte count from the pretreatment baseline value; 50% reduction in lymphadenopathy and/or = 50% reduction in the size of the liver and/or spleen AND one or more of the following Polymorphonuclear leukocytes > 1,500/uL or 50% improvement over baseline Platelets > 100,000/uL or 50% improvement over baseline Hemoglobin > 11.0 g/dL or 50% improvement over baseline	24 weeks	No
Secondary	Duration of Response		105 months	No