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

Primary Purpose

Leukemia, B-cell Leukemia, Chronic Leukemia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Alemtuzumab
Fludarabine
Cytoxan
Sponsored by
Steven E. Coutre
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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: Weight loss ≥ 10% body weight within the previous 6 months Extreme fatigue Fever greater than 100.5° F for ≥ 2 weeks without evidence of infection 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.

Sites / Locations

  • Stanford University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fludarabine, cytoxan, then alemtuzumab

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Duration of Response

Full Information

First Posted
September 28, 2005
Last Updated
September 25, 2014
Sponsor
Steven E. Coutre
Collaborators
Bayer
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1. Study Identification

Unique Protocol Identification Number
NCT00230282
Brief Title
Phase 2 Fludarabine, Cytoxan and FCCAM <Alemtuzumab> in Untreated B-Cell Chronic Lymphocytic Leukemia
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
July 2004 (undefined)
Primary Completion Date
December 2010 (Actual)
Study Completion Date
October 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Steven E. Coutre
Collaborators
Bayer

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, B-cell Leukemia, Chronic Leukemia, Chronic Lymphocytic Leukemia (CLL)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Fludarabine, cytoxan, then alemtuzumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Alemtuzumab
Other Intervention Name(s)
Campath, MabCampath, Campath-1H, Lemtrada, FCCam
Intervention Description
3 to 30 mg, IV
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Description
[(2R,3R,4S,5R)-5-(6-amino-2-fluoro-purin-9-yl)- 3,4-dihydroxy-oxolan-2-yl]methoxyphosphonic acid
Intervention Type
Drug
Intervention Name(s)
Cytoxan
Other Intervention Name(s)
Cyclophosphamide, cytophosphane, Endoxan, Neosar, Procytox, Revimmune
Intervention Description
(RS)-N,N-bis(2-chloroethyl)-1,3,2-oxazaphosphinan-2-amine 2-oxide
Primary Outcome Measure Information:
Title
Number of Subjects Maintaining Partial Response (PR) or Complete Response (CR)
Description
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
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Duration of Response
Time Frame
105 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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: Weight loss ≥ 10% body weight within the previous 6 months Extreme fatigue Fever greater than 100.5° F for ≥ 2 weeks without evidence of infection 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven Edward Coutre
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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