Trial Information

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

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 multicenter, 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.

PROJECTED ACCRUAL: A total of 84 patients will be accrued for this study.