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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00363090
First received: August 10, 2006
Last updated: September 19, 2013
Last verified: June 2009
  Purpose

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

Study Type: Interventional
Study Design: Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Toxicity as assessed by NCI Common Toxicity Criteria Version 3.0 [ Designated as safety issue: Yes ]
  • Safety [ Designated as safety issue: Yes ]
  • Dose-limiting toxicities [ Designated as safety issue: Yes ]
  • Pharmacokinetics of alemtuzumab [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Efficacy as assessed by clinical, radiologic, pathologic, and laboratory measurements [ Designated as safety issue: No ]
  • Overall response rate [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Effects of treatment on T- and B-cell reconstitution by flow cytometry at baseline and at 3, 6, and 12 months [ Designated as safety issue: No ]

Estimated Enrollment: 84
Study Start Date: September 2006
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00363090

Locations
Canada, British Columbia
St. Paul's Hospital at Providence Health Care - Vancouver Recruiting
Vancouver, British Columbia, Canada, V6Z 1Y6
Contact: Contact Person    604-806-9656      
Canada, Ontario
Margaret and Charles Juravinski Cancer Centre Recruiting
Hamilton, Ontario, Canada, N6A 4L6
Contact: Graeme Fraser, MD, FRCPC    905-575-7820      
London Regional Cancer Program at London Health Sciences Centre Recruiting
London, Ontario, Canada, N6A 4L6
Contact: Joy Mangel, MD    519-685-8615    joy.mangel@lhsc.on.ca   
Odette Cancer Centre at Sunnybrook Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Rena Buckstein, MD    416-480-5847    rena.buckstein@sunnybrook.ca   
Princess Margaret Hospital Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Michael R. Crump, MD, FRCPC    416-946-4567    michael.crump@uhn.on.ca   
Sponsors and Collaborators
Odette Cancer Centre at Sunnybrook
Investigators
Study Chair: Rena Buckstein, MD Odette Cancer Centre at Sunnybrook
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00363090     History of Changes
Other Study ID Numbers: CDR0000491451, TSRCC-164-2006
Study First Received: August 10, 2006
Last Updated: September 19, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
contiguous stage II adult diffuse large cell lymphoma
contiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
angioimmunoblastic T-cell lymphoma
anaplastic large cell lymphoma
stage II adult T-cell leukemia/lymphoma
stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, T-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Liposomal doxorubicin
Alemtuzumab
Doxorubicin
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on September 18, 2014