- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00280241
Protocol for the Treatment of Patients With Previously Untreated Chronic Lymphocytic Leukemia
January 5, 2016 updated by: Michael Boyiadzis, University of Pittsburgh
Phase II Clinical Protocol for the Treatment of Patients With Previously Untreated Chronic Lymphocytic Leukemia
This research study will look at the effects (good or bad) of administering cyclophosphamide, fludarabine, and rituximab.
Clinical studies with combination therapy have shown higher response rates than using single drugs, and this study will evaluate the side effects and effectiveness of this combination.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
This study is designed to expand on the highly successful combination of rituximab, fludarabine and cyclophosphamide for patients with previously untreated CLL.
Responses in the range of 90-98% with 55% complete responses are reported.
However, bone marrow toxicity has been a significant problem.
This trial is designed to reduce the bone marrow toxicity by decreasing the doses of fludarabine and cyclophosphamide, but doubling the dose of rituximab with a maintenance dose of rituximab for up to two years, to maintain or even enhance efficacy.
Study Type
Interventional
Enrollment (Actual)
65
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15232
- Hillman Cancer Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Diagnosis of CD20 + CLL
- Peripheral blood absolute lymphocyte count of > 5,000/mm3 obtained within 2 weeks prior to randomization.
- The lymphocytosis must consist of small to moderate size lymphocytes, with ≤55% (no greater than 55%) prolymphocytes, atypical lymphocytes, or lymphoblasts morphologically.
- Phenotypically characterized CD20 + CLL defined as: 1) the predominant population of cells share B-cell antigens with CD5 in the absence of other pan-T-celI markers (CD3, CD2, etc.); 2) B-cell expresses either kappa or lambda light chains; and 3) surface immunoglobulin (slg) with low-cell surface density expression.
- Splenomegaly, hepatomegaly or lymphadenopathy are not required for the diagnosis of CLL.
- Must require chemotherapy. Indications for chemotherapy are one or more of the following:
- One or more of the following disease-related symptoms
- Weight loss >10% within the previous 6 months.
- Fevers of greater than 100.0° F for 2 weeks without evidence of infection.
- Night sweats without evidence of infection.
- Evidence of progressive marrow failure as manifested by the development of or worsening of anemia (< 10 g/dl) and/or thrombocytopenia (< 100,000/mm3).
- Massive (i.e., > 6 cm below left costal margin) or progressive splenomegaly.
- Massive nodes or clusters (i.e., > 10 cm in longest diameter) or progressive
- adenopathy.
- Progressive lymphocytosis with an increase of> 50% over 2 month period, or an anticipated doubling time of less than 6 months.
- NOTE: Marked hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for active disease are not sufficient for protocol therapy.
- Serum creatinine <1.5 mg/dl.
- Bilirubin must be <2 mg/dl, unless secondary to tumor, obtained within 2 weeks prior to randomization.
- Age >18 years.
- Not pregnant (confirmed by serum pregnancy test in females of reproductive potential) or breast feeding, because it is unknown what effect these drugs will have on children.
- ECOG performance status 0-2.
- AST or ATL >2x upper limit of normal unless related to CLL.
- Subject has provided written informed consent.
Exclusion criteria:
- Subjects with autoimmune anemia or thrombocytopenia are not eligible.
- No prior cytotoxic chemotherapy. Patients with a history of steroid treatment for CLL, autoimmune hemolytic anemia, or autoimmune thrombocytopenia are not eligible.
- Subjects with active infections requiring oral or intravenous antibiotics until resolution of the infection and completion of therapeutic antibiotics.
- Women of childbearing potential and sexually active males who refuse to use an accepted and effective method of contraception.
- Subjects with a second malignancy other than basal cell carcinoma of the skin or in situ carcinoma of the cervix are not eligible unless the tumor was treated with curative intent at least two years previously.
- History of HIV
- CNS disease
- History of psychiatric disorder that would make it difficult to enroll and follow the patient on trial.
- New York Heart Classification III or IV heart disease.
- Hepatitis BsAg or Hepatitis C positive.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: FLUDARABINE, CYCLOSPHOSPHAMIDE AND RITUXIMAB
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Fludarabine is usually administered by IV infusion over 30 minutes or longer.
The dosage is a solution of 20 mg/mI.
IV infusion over 1 hour.
First Infusion: The rituximab solution for infusion should be administered intravenously at an initial rate of 50 mg/hr.
Subsequent rituximab infusions can be administered at an initial rate of 100 mg/hr, and increased by 100 mg/hr increments at 30-minute intervals, to a maximum of 400 mg/hr as tolerated.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Tolerability of Rituximab, Cyclophosphamide and Fludarabine in Patients With Previously Untreated CLL/SLL
Time Frame: Duration of treatment on study
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The number of patients who experience any grade 3-5 toxicity.
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Duration of treatment on study
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Efficacy of Rituximab, Cyclophosphamide and Fludarabine in Patients With Previously Untreated CLL/SLL
Time Frame: Three months after the sixth cycle (9 months)
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The number of patients who experience a complete clinical response.
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Three months after the sixth cycle (9 months)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival Rate
Time Frame: Five years after starting rituximab, cyclophosphamide and fludarabine
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The percentage of participants who are still alive.
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Five years after starting rituximab, cyclophosphamide and fludarabine
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Duration of Response
Time Frame: From complete response to the time of progressive disease, death or last clinical examination
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The length of time for which the complete response is maintained.
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From complete response to the time of progressive disease, death or last clinical examination
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Micahel Boyiadzis, MD, University of Pittsburgh Medical Center
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2004
Primary Completion (Actual)
February 1, 2008
Study Completion (Actual)
January 1, 2013
Study Registration Dates
First Submitted
January 19, 2006
First Submitted That Met QC Criteria
January 19, 2006
First Posted (Estimate)
January 20, 2006
Study Record Updates
Last Update Posted (Estimate)
February 4, 2016
Last Update Submitted That Met QC Criteria
January 5, 2016
Last Verified
January 1, 2016
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
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Immunological
- Cyclophosphamide
- Rituximab
- Fludarabine
Other Study ID Numbers
- 03-136
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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