Alemtuzumab Combined With Etoposide, Vincristine, Doxorubicin, Cyclophosphamide, and Prednisone in Treating Patients Who Have Not Received Chemotherapy For T-Cell or NK-Cell Lymphoma - Full Text View

Sponsor:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00072254

Purpose

RATIONALE: Drugs used in chemotherapy, such as etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone, use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as alemtuzumab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining monoclonal antibody therapy with chemotherapy may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of alemtuzumab when given together with combination chemotherapy in treating patients who have not previously received chemotherapy for T-cell or NK-Cell lymphoma.

Condition	Intervention	Phase
Lymphoma	Biological: alemtuzumab Biological: filgrastim Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Drug: prednisone Drug: vincristine sulfate	Phase I

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Pilot Trial of Alemtuzumab and Dose-Adjusted EPOCH in Chemotherapy-Naïve Aggressive T and NK-Cell Lymphomas

Resource links provided by NLM:

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

Primary Outcome Measures:

Toxicity during treatment [ Designated as safety issue: Yes ]
Maximum tolerated dose during treatment [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Anti-tumor activity at the end of treatment [ Designated as safety issue: No ]

Estimated Enrollment:	24
Study Start Date:	September 2003
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the toxicity of alemtuzumab and etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone (EPOCH) in patients with chemotherapy-naïve CD52-expressing aggressive T- or NK-cell lymphoma.
Determine the maximum tolerated dose of alemtuzumab when administered with EPOCH chemotherapy in these patients.

Secondary

Determine, preliminarily, the antitumor activity of this regimen in these patients.

OUTLINE: This is a pilot, dose-escalation study of alemtuzumab.

Patients receive alemtuzumab IV over 12 hours on day 1 and EPOCH chemotherapy comprising etoposide IV, doxorubicin IV, and vincristine IV continuously over 96 hours on days 1-4; cyclophosphamide IV over 15 minutes on day 5; and oral prednisone twice daily on days 0-5. Patients also receive filgrastim subcutaneously on day 6. Treatment repeats every 21 days for 6-8 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.

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A maximum of 24 patients will be accrued to this study within 2.5 years.

Eligibility

Ages Eligible for Study:	17 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of aggressive T- or NK-cell lymphoma, including, but not limited to any of the following:
- Peripheral T-cell lymphoma not otherwise specified
- Gamma-delta hepatosplenic T-cell lymphoma
- Subcutaneous panniculitis-like T-cell lymphoma
CD52-positive disease by pathology or flow cytometry
- T- and NK-cell malignancy without accessible tissue for flow cytometry analysis allowed
Chemotherapy-naïve disease
No anaplastic large cell lymphoma (ALCL) except alk-negative ALCL
No T-cell precursor disease

PATIENT CHARACTERISTICS:

Age

17 and over

Performance status

Not specified

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count at least 1,000/mm^3*
Platelet count at least 75,000/mm^3* NOTE: *Unless due to organ involvement by tumor

Hepatic

Bilirubin less than 2.0 mg/dL (unless due to Gilbert's syndrome)
AST and ALT no greater than 3 times upper limit of normal (ULN) (6 times ULN for patients on hyperalimentation)

Renal

Creatinine no greater than 1.5 mg/dL OR
Creatinine clearance at least 60 mL/min

Cardiovascular

No active symptomatic ischemic heart disease within the past year
No myocardial infarction within the past year
No congestive heart failure within the past year

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
HIV negative
No other concurrent medical condition or infection that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

Prior biologic therapy allowed
No other concurrent biologic therapy

Chemotherapy

See Disease Characteristics
No other concurrent chemotherapy

Endocrine therapy

Prior steroids allowed
No other concurrent endocrine therapy

Radiotherapy

No prior or concurrent radiotherapy

Surgery

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00072254

Locations

United States, Maryland
NCI - Center for Cancer Research
Bethesda, Maryland, United States, 20892
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Study Chair:

John E. Janik, MD

NCI - Metabolism Branch;MET

More Information

Additional Information:

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

Web site for additional information This link exits the ClinicalTrials.gov site

Publications:

Janik JE, Dunleavy K, Pittaluga S, et al.: A pilot trial of campath-1H and dose-adjusted EPOCH in CD52-expressing aggressive T-Cell malignancies. [Abstract] Blood 106 (11): A-3348, 2005.

Study ID Numbers:	CDR0000339370, NCI-03-C-0304
Study First Received:	November 4, 2003
Last Updated:	March 31, 2009
ClinicalTrials.gov Identifier:	NCT00072254 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage I cutaneous T-cell non-Hodgkin lymphoma
contiguous stage II adult diffuse large cell lymphoma
contiguous stage II adult diffuse mixed cell lymphoma
contiguous stage II adult diffuse small cleaved 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 small cleaved cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
angioimmunoblastic T-cell lymphoma
stage I adult T-cell leukemia/lymphoma
stage II adult T-cell leukemia/lymphoma

stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
stage III adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
stage I adult diffuse large cell lymphoma
stage I adult diffuse mixed cell lymphoma
stage I adult diffuse small cleaved cell lymphoma
anaplastic large cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult T-cell leukemia/lymphoma

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
Etoposide phosphate
Alemtuzumab
Therapeutic Uses
Etoposide
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 November 27, 2009