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

September 19, 2013 updated by: Toronto Sunnybrook Regional Cancer Centre

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

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.

Study Overview

Status

Unknown

Conditions

Lymphoma

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

Phase

Phase 2
Phase 1

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

Canada
- British Columbia
  - Vancouver, British Columbia, Canada, V6Z 1Y6
    - Recruiting
    - St. Paul's Hospital at Providence Health Care - Vancouver
    - Contact:
      
      Contact Person
      
      Phone Number: 604-806-9656
- Ontario
  - Hamilton, Ontario, Canada, N6A 4L6
    - Recruiting
    - Margaret and Charles Juravinski Cancer Centre
    - Contact:
      
      Graeme Fraser, MD, FRCPC
      
      Phone Number: 905-575-7820
  - London, Ontario, Canada, N6A 4L6
    - Recruiting
    - London Regional Cancer Program at London Health Sciences Centre
    - Contact:
      
      Joy Mangel, MD
      
      Phone Number: 519-685-8615
      
      Email: joy.mangel@lhsc.on.ca
  - Toronto, Ontario, Canada, M5G 2M9
    - Recruiting
    - Princess Margaret Hospital
    - Contact:
      
      Michael R. Crump, MD, FRCPC
      
      Phone Number: 416-946-4567
      
      Email: michael.crump@uhn.on.ca
  - Toronto, Ontario, Canada, M4N 3M5
    - Recruiting
    - Odette Cancer Centre at Sunnybrook

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

Genders Eligible for Study

All

Description

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

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
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Toronto Sunnybrook Regional Cancer Centre

Investigators

Study Chair: Rena Buckstein, MD, Toronto Sunnybrook Regional Cancer Centre

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

September 1, 2006

Primary Completion (Anticipated)

December 1, 2010

Study Registration Dates

First Submitted

August 10, 2006

First Submitted That Met QC Criteria

August 10, 2006

First Posted (Estimate)

August 15, 2006

Study Record Updates

Last Update Posted (Estimate)

September 20, 2013

Last Update Submitted That Met QC Criteria

September 19, 2013

Last Verified

June 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

CDR0000491451
TSRCC-164-2006

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.