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

Sponsored by:	Edmond Odette Cancer Centre at Sunnybrook
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00363090

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 I Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
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:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma

Drug Information available for: Cyclophosphamide Prednisone Vincristine Doxorubicin Doxorubicin hydrochloride Myocet Campath Alemtuzumab Vincristine sulfate

U.S. FDA Resources

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

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
Edmond Odette Cancer Centre at Sunnybrook	Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Rena Buckstein, MD 416-480-5847 rena.buckstein@sunnybrook.ca
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
Margaret and Charles Juravinski Cancer Centre	Recruiting
Hamilton, Ontario, Canada, N6A 4L6
Contact: Graeme Fraser, MD, FRCPC 905-575-7820
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

Edmond Odette Cancer Centre at Sunnybrook

Investigators

Study Chair:

Rena Buckstein, MD

Edmond Odette Cancer Centre at Sunnybrook

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000491451, TSRCC-164-2006
Study First Received:	August 10, 2006
Last Updated:	July 1, 2009
ClinicalTrials.gov Identifier:	NCT00363090 History of Changes
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

Study placed in the following topic categories:

Anti-Inflammatory Agents
Prednisone
Immunologic Factors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Cyclophosphamide
Hormones
Lymphoma, T-Cell, Peripheral
Lymphoma, Small Cleaved-cell, Diffuse
Anti-Bacterial Agents
Leukemia
Lymphoma, T-Cell
Alemtuzumab
Lymphoma, Large-Cell, Anaplastic
Aggression

Lymphoma, Large-cell
Alkylating Agents
Lymphoma
Lymphoma, Large B-Cell, Diffuse
Peripheral T-cell Lymphoma
Immunoproliferative Disorders
Antineoplastic Agents, Hormonal
Leukemia-Lymphoma, Adult T-Cell
Immunoblastic Lymphadenopathy
Vincristine
Antimitotic Agents
Glucocorticoids
Immunosuppressive Agents
Doxorubicin
Lymphatic Diseases

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Prednisone
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Cyclophosphamide
Antibiotics, Antineoplastic
Hormones
Lymphoma, T-Cell, Peripheral
Alemtuzumab
Lymphoma, T-Cell
Therapeutic Uses
Lymphoma

Alkylating Agents
Immunoproliferative Disorders
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Mitosis Modulators
Vincristine
Antimitotic Agents
Glucocorticoids
Immunosuppressive Agents
Doxorubicin
Pharmacologic Actions
Lymphatic Diseases
Neoplasms
Tubulin Modulators

ClinicalTrials.gov processed this record on September 02, 2009