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

Sponsor

Toronto Sunnybrook Regional Cancer Centre (Other)

Overall Status

Unknown status

CT.gov ID

NCT00363090

Collaborator

(none)

Enrollment

Locations

16.8

Patients Per Site

Study Details

Study Description

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, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, 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/II trial is studying the side effects and best dose of alemtuzumab when given together with combination chemotherapy and to see how well they work in treating patients with newly diagnosed aggressive stage II, stage III, or stage IV T-cell non-Hodgkin's lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: alemtuzumab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate Other: flow cytometry Other: pharmacological study	Phase 1/Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

84 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2006

Anticipated Primary Completion Date :

Dec 1, 2010

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed aggressive peripheral T-cell non-Hodgkin's lymphoma (NHL), including the following nodal or extranodal subtypes:
Nodal:
Angioimmunoblastic lymphadenopathy
ALK 1-negative anaplastic large cell NHL
Peripheral T-cell lymphoma not otherwise specified
Extranodal:
Hepatosplenic NHL
Enteropathy-associated NHL
Panniculitic NHL
Stage II-IV disease
Newly diagnosed, CD52+ disease
Measurable or evaluable disease
No known CNS involvement with lymphoma
No nasal natural killer T-cell NHL

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy > 4 months
Absolute neutrophil count ≥ 1,000/mm³*
Platelet count ≥ 75,000/mm³*
Hemoglobin ≥ 8.5 g/dL*
Bilirubin < 2.0 mg/dL
Alkaline phosphatase ≤ 2 times upper limit of normal (ULN)
AST or ALT < 2 times ULN
Creatinine < 1.5 mg/dL*
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No known hypersensitivity to any of the study drugs
No serious illnesses that would preclude compliance with study requirements
No known HIV positivity
No other preexisting immunodeficiency (e.g., post-organ transplant)
No other malignancy within the past 5 years except cervical carcinoma in situ or nonmelanoma skin cancer NOTE: *Unless directly attributable to NHL

PRIOR CONCURRENT THERAPY:

No prior chemotherapy or radiotherapy
Up to 7 days of prednisone preceding initiation of chemotherapy allowed
No other concurrent chemotherapy, radiotherapy, or immunotherapy
No other concurrent corticosteroids except dexamethasone used as an antiemetic for a brief period

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Paul's Hospital at Providence Health Care - Vancouver	Vancouver	British Columbia	Canada	V6Z 1Y6
2	Margaret and Charles Juravinski Cancer Centre	Hamilton	Ontario	Canada	N6A 4L6
3	London Regional Cancer Program at London Health Sciences Centre	London	Ontario	Canada	N6A 4L6
4	Odette Cancer Centre at Sunnybrook	Toronto	Ontario	Canada	M4N 3M5
5	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9