Alemtuzumab and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV T-Cell Non-Hodgkin's Lymphoma

Titre officiel

Alemtuzumab and CHOP Chemotherapy for Aggressive Histology Peripheral T Cell Lymphomas: A Multi-Centre Phase I and II Study

Sommaire:

Les anticorps monoclonaux, tel l’alemtuzumab, peuvent inhiber la croissance tumorale de différentes façons. Certains inhibent la capacité des cellules cancéreuses de se multiplier et d’essaimer. D’autres localisent les cellules cancéreuses et aident à les tuer ou transportent vers elles des substances qui les tuent. Les médicaments utilisés pour la chimiothérapie, telles la cyclophosphamide, la doxorubicine, la vincristine et la prednisone, agissent de différentes façons pour empêcher la multiplication des cellules cancéreuses, soit en les tuant, soit en les empêchant de croître. L’administration d’alemtuzumab combinée à la chimiothérapie d’association pourrait tuer un plus grand nombre de cellules cancéreuses.

Cet essai de phases I et II vise à évaluer les effets secondaires de l’alemtuzumab et la dose la plus efficace de ce médicament lorsqu’il est administré en concomitance avec une chimiothérapie d’association ainsi que l’efficacité de ces produits dans le traitement des patients atteints d’un lymphome non hodgkinien à cellules T agressif de stade II, III ou IV nouvellement diagnostiqué.

Description de l'essai

Primary Outcome:

• Toxicity as assessed by NCI Common Toxicity Criteria Version 3.0
• Safety
• Dose-limiting toxicities
• Pharmacokinetics of alemtuzumab

Secondary Outcome:

• Efficacy as assessed by clinical, radiologic, pathologic, and laboratory measurements
• Overall response rate
• Progression-free survival
• Overall survival
• Effects of treatment on T- and B-cell reconstitution by flow cytometry at baseline and at 3, 6, and 12 months

OBJECTIVES:
Primary

• Establish the safety and dose-limiting toxicities of alemtuzumab in combination with cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (CHOP) chemotherapy in patients with newly diagnosed, stage II-IV aggressive peripheral T-cell non-Hodgkin's lymphoma.

• Measure the pharmacokinetics of alemtuzumab using different subcutaneous doses and schedules to determine the dose with the highest achievable drug levels with acceptable toxicities worthy of further investigation.
  

Secondary

• Determine the efficacy of alemtuzumab in combination with CHOP chemotherapy using escalating doses and 2 different drug schedules, as defined by overall response rate, progression-free survival, and overall survival.

• Measure the effects of this regimen on T-cell reconstitution and cytomegalovirus reactivation.

OUTLINE:

This is a multicentre, phase I, dose-escalation study of alemtuzumab followed by an open-label, phase II study.

• Phase I: 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) on day 1 OR on days 1, 8, and 15. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of alemtuzumab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

• Phase II: Patients receive CHOP chemotherapy and alemtuzumab (at the MTD determined in phase I) as in phase I (on the most effective regimen). Patients undergo blood collection at baseline, periodically during study treatment, and after completion of study treatment for pharmacokinetics and other correlative studies. Samples are examined for presence of cytomegalovirus antigen and by flow cytometry for B- and T-cell quantification. After completion of study treatment, patients are followed periodically.
  

Voir cet essai sur ClinicalTrials.gov