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

NCT ID: NCT00230282

Last Updated: 2014-10-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-07-31
• Study Completion Date: 2011-10-31

Brief 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.

Detailed 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.

Conditions

Leukemia; B-cell Leukemia; Chronic Leukemia; Chronic Lymphocytic Leukemia (CLL)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fludarabine, cytoxan, then alemtuzumab

Fludarabine and cyclophosphamide days 1 to 3 for six 28-day cycles. Minimal residual disease positive responders continued on-treatment to receive alemtuzumab 30 mg weekly. MRD negative responders were observed.

Group Type: EXPERIMENTAL

Alemtuzumab

Intervention Type: DRUG

3 to 30 mg, IV

Fludarabine

Intervention Type: DRUG

\[(2R,3R,4S,5R)-5-(6-amino-2-fluoro-purin-9-yl)- 3,4-dihydroxy-oxolan-2-yl\]methoxyphosphonic acid

Cytoxan

Intervention Type: DRUG

(RS)-N,N-bis(2-chloroethyl)-1,3,2-oxazaphosphinan-2-amine 2-oxide

Interventions

Alemtuzumab

3 to 30 mg, IV

Intervention Type: DRUG

Fludarabine

\[(2R,3R,4S,5R)-5-(6-amino-2-fluoro-purin-9-yl)- 3,4-dihydroxy-oxolan-2-yl\]methoxyphosphonic acid

Intervention Type: DRUG

Cytoxan

(RS)-N,N-bis(2-chloroethyl)-1,3,2-oxazaphosphinan-2-amine 2-oxide

Intervention Type: DRUG

Other Intervention Names

Campath; MabCampath; Campath-1H; Lemtrada; FCCam; Fludara; Cyclophosphamide; cytophosphane; Endoxan; Neosar; Procytox; Revimmune

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

Steven E. Coutre

OTHER

Sponsor Role: lead

Responsible Party

Steven E. Coutre

Associate Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Steven Edward Coutre

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

Countries

United States

Other Identifiers

31185

Identifier Type: OTHER

Identifier Source: secondary_id

80071

Identifier Type: OTHER

Identifier Source: secondary_id

HEMCLL0001

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-13053

Identifier Type: -

Identifier Source: org_study_id