- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00098670
Fludarabine, Rituximab, and Alemtuzumab in Treating Patients With Chronic Lymphocytic Leukemia
A Phase II Study of Fludarabine + Rituximab Induction Followed by Alemtuzumab (Campath-1H, NSC #715969, IND #10864) Administered Subcutaneously as Consolidation in Untreated Patients With B-Cell Chronic Lymphocytic Leukemia
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the rate of complete response and toxicity of concurrent treatment with fludarabine and rituximab followed by consolidative alemtuzumab in patients with previously untreated, but symptomatic, CLL.
II. To determine if alemtuzumab improves the CR rate with acceptable toxicity when administered as consolidation therapy following induction therapy with fludarabine and rituximab.
III. To estimate the progression-free and overall survival of high risk (VH gene unmutated and those with p53 dysfunction) and low-risk (others) patients following therapy with fludarabine and rituximab induction and consolidative alemtuzumab.
IV. To determine the frequency of molecular (PCR) remission following fludarabine and rituximab induction therapy and alemtuzumab consolidation therapy and if this serves as a surrogate marker for prolonged progression-free and overall survival.
SECONDARY OBJECTIVES:
I. To determine the effect of concurrent treatment with fludarabine and rituximab followed by consolidative alemtuzumab on recovery of T-cells, NK cells, and serum immunoglobulin levels.
II. To determine clinical and molecular features that predict for poor response to fludarabine and rituximab induction and subsequent alemtuzumab consolidation therapy.
III. To assess preliminarily the molecular features of CLL at relapse in patients responding to chemoimmunotherapy for CLL.
IV. To determine the frequency of patients who remain at high risk for progression of CLL despite this therapy and who are thus eligible for nonmyeloablative stem cell transplantation studies such as CALGB 109901.
V. To perform limited rituximab pharmacokinetics to determine the ideal schedule of administration for a subsequent rituximab maintenance treatment approach following induction therapy with fludarabine and rituximab.
OUTLINE:
Patients receive induction therapy comprising rituximab IV over 4 hours on days 1, 3, and 5 of course 1 and day 1 of all subsequent courses and fludarabine IV over 30 minutes on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression.
Approximately 4 months after completion of induction therapy, patients achieving a partial response, nodular partial response, or stable disease receive consolidation therapy comprising alemtuzumab subcutaneously on days 1-3. Treatment repeats weekly for up to 6 courses in the absence of disease progression.
Patients are followed at 2 months, every 3 months for 1 year, and then every 6 months for 7 years from study entry.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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-
Illinois
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Chicago, Illinois, United States, 60606
- Cancer and Leukemia Group B
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Ohio
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Columbus, Ohio, United States, 43210
- Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Specific Diagnosis of B-Cell CLL
- An absolute lymphocytosis of > 5,000/μL
- Morphologically, the lymphocytes must appear mature with < 55% prolymphocytes
- Bone marrow examination must include at least a unilateral aspirate and biopsy; the aspirate smear must show > 30% of all nucleated cells to be lymphoid or the bone marrow core biopsy must show lymphoid infiltrates compatible with marrow involvement by CLL; the overall cellularity must be normocellular or hypercellular
- Local institution lymphocyte phenotype must reveal a predominant B-cell monoclonal population sharing a B-cell marker (CD19, CD20, CD23) with the CD5 antigen, in the absence of other pan-T-cell markers; additionally, the B-cells must be monoclonal with regard to expression of either κ or λ and have surface immunoglobulin expression of low density; patients with bright surface immunoglobulin levels must have CD23 co-expression
- Patients must be in the intermediate- or high-risk categories of the modified three-stage Rai staging system (i.e., stages I, II, III, or IV)
Patients in the intermediate-risk group must have evidence of active disease as demonstrated by at least one of the following criteria:
- Massive or progressive splenomegaly, hepatomegaly and/or lymphadenopathy;
- Presence of weight loss > 10% over the preceding 6 month period;
- Grade 2 or 3 fatigue;
- Fevers > 100.5°F or night sweats for greater than 2 weeks without evidence of infection;
- Progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of less than 6 months
- No prior therapy for CLL including corticosteroids for autoimmune complications that have developed since the initial diagnosis of CLL
- No medical condition requiring chronic use of oral corticosteroids
- Performance Status 0 - 2
- Due to alterations in host immunity, patients with HIV may not be enrolled
- Due to the unknown teratogenic potential of alemtuzumab, pregnant or nursing women may not be enrolled; women and men of reproductive potential should agree to use an effective means of birth control
- Creatinine =< 1.5 x upper limit of institutional normal value
- Coomb's Testing NEGATIVE
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Treatment (alemtuzumab, rituximab, fludarabine phosphate)
Patients receive induction therapy comprising rituximab IV over 4 hours on days 1, 3, and 5 of course 1 and day 1 of all subsequent courses and fludarabine IV over 30 minutes on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression. Approximately 4 months after completion of induction therapy, patients achieving a partial response, nodular partial response, or stable disease receive consolidation therapy comprising alemtuzumab subcutaneously on days 1-3. Treatment repeats weekly for up to 6 courses in the absence of disease progression. |
Given IV
Other Names:
Given IV
Other Names:
Given SC
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With a Complete Response After Treatment With Fludarabine & Rituximab Followed by Alemtuzumab
Time Frame: Duration of treatment (up to 13.5 months)
|
A complete response, as defined by the National Cancer Institute Working Group (NCIWG): - CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate & biopsy |
Duration of treatment (up to 13.5 months)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With a Complete or Partial Response After Induction Therapy With Fludarabine & Rituximab
Time Frame: Up to 9 months
|
Response, as defined by the National Cancer Institute Working Group (NCIWG): CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate & biopsy PR: 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus ≥1 of the following: ≥1500/μL polymorphonuclear leukocytes, >100,000/μL platelets, >11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions |
Up to 9 months
|
2 Year Progression Free Survival
Time Frame: 2 years from registration
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Percentage of patients who were alive and progression free at 2 years.
The 2-year progression free survival was estimated using the Kaplan Meier method.
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2 years from registration
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2 Year Survival
Time Frame: 2 years from registration
|
Percentage of participants who were alive at 2 years.
The 2 year survival was estimated using the Kaplan Meier method.
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2 years from registration
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Number of Participants With Severe Non-Hematologic Adverse Events During Treatment With Alemtuzumab
Time Frame: 6 weeks beginning at study week 36
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The National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Version 2.0 was used to evaluate toxicity. Severe Adverse events are defined as grade 3, 4 or 5, at least possibly related to treatment. Grade 1: mild; Grade 2: moderate; Grade 3: Severe; Grade 4: Life Threatening; Grade 5: Death. |
6 weeks beginning at study week 36
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Thomas Lin, Cancer and Leukemia Group B
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Leukemia, B-Cell
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antibodies
- Immunoglobulins
- Rituximab
- Antibodies, Monoclonal
- Antineoplastic Agents, Immunological
- Fludarabine
- Fludarabine phosphate
- Alemtuzumab
Other Study ID Numbers
- NCI-2012-02812 (REGISTRY: CTRP (Clinical Trial Reporting Program))
- U10CA031946 (U.S. NIH Grant/Contract)
- P30CA014236 (U.S. NIH Grant/Contract)
- CDR0000398139
- CALGB-10101 (OTHER: CTEP)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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