Alemtuzumab and Combination Chemotherapy in Treating Patients With Stage I, Stage II, Stage III, or Stage IV Peripheral T-Cell Lymphoma
- Conditions
- LymphomaSmall Intestine Cancer
- Registration Number
- NCT00562068
- Lead Sponsor
- Cancer Research UK
- Brief Summary
RATIONALE: Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from growing. Giving alemtuzumab together with combination chemotherapy may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of alemtuzumab when given together with combination chemotherapy and to see how well it works in treating patients with stage I , stage II , stage III, or stage IV peripheral T-cell lymphoma.
- Detailed Description
OBJECTIVES:
Primary
* To determine the feasibility of adding alemtuzumab to standard cyclophosphamide, doxorubicin hydrochloride, vincristine, and oral prednisolone (CHOP) chemotherapy in patients with stage I-IV peripheral T-cell lymphoma (PTCL).
* To assess the side effect profile and early and late toxicities of this regimen in a standard dose-escalation design, and to establish an appropriate dose level for future studies.
Secondary
* To document response rates and disease-free survival of patients treated with this regimen, and to compare these findings with those of historical controls.
* To monitor immune reconstitution after therapy.
* To determine the pharmacokinetics of subcutaneous alemtuzumab when given in combination with CHOP chemotherapy.
* To more clearly define the CD52 expression profile in these tumors and to investigate phenotypic variations in PTCL.
* To document changes (if any) in levels of Epstein-Barr virus copy number by polymerase chain reaction during CHOP-alemtuzumab therapy.
OUTLINE: This is a multicenter, dose escalation of alemtuzumab study.
Patients receive CHOP chemotherapy comprising cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Patients also receive alemtuzumab subcutaneously (SC) 1-3 times a week for up to 6 doses per course. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo blood collection at baseline, periodically during study treatment, and after completion of study therapy for pharmacokinetics and other correlative studies to monitor cellular immunity. Blood samples are examined by polymerase chain reaction to detect cytomegalovirus antigen and to monitor Epstein-Barr virus copy number. Samples are also analyzed by flow cytometry to quantify circulating B- and T-cells, NK-cells, monocytes, and dendritic-cells.
After completion of study therapy, patients are followed every 3 months for the first year, every 6 months for the second year, and then yearly thereafter.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 30
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Immediate toxicity (incidence of infusion-related reactions) Hematopoietic toxicity (number of cycles of therapy associated with neutrophils < 0.5e9/L or platelets < 50e9/L) Incidence of infection (number of days with fever ≥ 38 degrees C, days of intravenous antibiotics, number of inpatient days, number of episodes of cytomegalovirus reactivation)
- Secondary Outcome Measures
Name Time Method Epstein-Barr virus copy number (measured retrospectively) Disease response (remission rate [complete response and partial response]) Disease outcome (time to progression and overall survival at 2 years from completion of therapy) Immune reconstitution (time to recover peripheral blood CD4 count to 0.2 e9/L) Relative dose intensity Pharmacokinetics assessment of alemtuzumab trough levels before each cycle of treatment
Trial Locations
- Locations (5)
Leeds General Infirmary
🇬🇧Leeds, England, United Kingdom
Royal Marsden - London
🇬🇧London, England, United Kingdom
Christie Hospital
🇬🇧Manchester, England, United Kingdom
King's College Hospital
🇬🇧London, England, United Kingdom
Torbay Hospital
🇬🇧Torbay Devon, England, United Kingdom