Alefacept in Treating Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma or Peripheral T-Cell Non-Hodgkin's Lymphoma - Full Text View

Sponsor:	Mayo Clinic
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Mayo Clinic
ClinicalTrials.gov Identifier:	NCT00438802

Purpose

RATIONALE: Combinations of biological substances in alefacept may be able to carry cancer-killing substances directly to cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of alefacept in treating patients with relapsed or refractory cutaneous T-cell lymphoma or peripheral T-cell non-Hodgkin's lymphoma.

Condition	Intervention	Phase
Lymphoma	Drug: Alefacept	Phase I

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I Study of Alefacept (AmeviveTM) in the Treatment of Cutaneous T-cell Lymphoma and Peripheral T-cell NHL

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Alefacept

U.S. FDA Resources

Further study details as provided by Mayo Clinic:

Primary Outcome Measures:

Tolerability [ Time Frame: 9/21/2006 - 7/06/2010 ] [ Designated as safety issue: Yes ]
Immunostimulation [ Time Frame: 9/22/2006 - 6/08/2010 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Clinical response [ Time Frame: 1/05/2007 - 2/25/2011 ] [ Designated as safety issue: No ]

Estimated Enrollment:	24
Study Start Date:	March 2006
Estimated Study Completion Date:	May 2013
Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: alefacept Determine both the maximum tolerated dose level as well as the optimal immunologic dose and toxicity.	Drug: Alefacept Dose escalation theme. 0.075mg/kg by IV Weekly x 8 to 0.30mg/kg IV Weekly x 8 Other Name: Amevive

Detailed Description:

OBJECTIVES:

Primary

Determine the maximum tolerated dose or the optimal immunologic dose of alefacept in patients with relapsed or refractory cutaneous T-cell lymphoma or peripheral T-cell non-Hodgkin's lymphoma.

Secondary

Determine if antitumor activity of this drug exists in these patients.

OUTLINE: This is a multicenter, dose-escalation study.

Induction therapy: Patients receive alefacept IV over 2-5 minutes once weekly for up to 8 weeks in the absence of disease progression or unacceptable toxicity. Patients with stable disease or complete or partial response after induction therapy proceed to maintenance therapy.

Cohorts of 6 patients receive escalating doses of alefacept until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. The optimal immunologic dose is defined as the dose that does not exceed the MTD, has the highest alefacept level, and achieves saturation of CD2 receptors.

Maintenance therapy: Patients receive alefacept IV on day 1. Treatment repeats every 4 weeks for 10-12 courses in the absence of disease progression or unacceptable toxicity.

Patients who experience disease progression during maintenance therapy may receive reinduction therapy* comprising 4 weekly doses of alefacept. The patient then proceeds to a second maintenance phase in the absence of disease progression.

NOTE: *Only 1 reinduction allowed.

Patients undergo blood and tissue collection periodically for pharmacological studies. Blood serum is analyzed for alefacept concentration, cytokine concentration, CD16 polymorphisms, and CD2 saturation via flow cytometry.

After completion of study treatment, patients are followed every 3 months for up to 3 years and then periodically thereafter.

PROJECTED ACCRUAL: A total of 24 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 cutaneous T-cell lymphoma (CTCL) or peripheral T-cell non-Hodgkin's lymphoma
- Diagnostic biopsies must have been obtained within the past 6 months
Relapsed or refractory disease
- Patients with CTCL must have failed ≥ 2 skin-directed therapies
  - No limit on the number of prior therapies
Measurable disease, defined as at least 1 bidimensionally measurable lesion > 2 cm by CT scan, MRI, physical exam, or photograph with appended ruler
- At least 2 bidimensionally measurable target lesions required for patients with skin lesions only
No CNS lymphoma

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Absolute neutrophil count ≥ 1,000/mm^3
Platelet count ≥ 75,000/mm^3
Hemoglobin ≥ 9 g/dL
Total bilirubin ≤ 2 times upper limit of normal (ULN) OR direct bilirubin ≤ 1.5 times ULN
AST ≤ 3 times ULN (≤ 5 times ULN if liver involvement)
Creatinine ≤ 2 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Willing to provide all research blood samples as required by the protocol
Willing to undergo repeat biopsy of either an accessible skin lesion or lymph node, if there are no circulating sezary cells, for the purpose of research studies (patients without easily accessible lesions are not required to have a repeat biopsy solely for research purposes but must be willing to provide a portion of the on-study biopsy or a previous lymphoma biopsy, if available)
No known congenital or acquired immunodeficiency syndromes, including HIV
No known active viral hepatitis or tuberculosis infection
No uncontrolled infection
No other uncontrolled serious medical condition unrelated to lymphoma (e.g., cardiac arrhythmia or diabetes)
No other active malignancies
No history of serious allergic reaction to citrate or glycine

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
More than 3 weeks since prior cytotoxic chemotherapy
More than 3 weeks since prior denileukin diftitox
More than 3 weeks since prior radiotherapy (less than 3 weeks if the acute side effects of this therapy are resolved)
More than 2 weeks since prior oral corticosteroids (unless being used to treat adrenal insufficiency)
More than 2 weeks since prior phototherapy, including ultraviolet B and psoralen with ultraviolet A
More than 1 week since prior biologic therapy
No concurrent chemotherapy, other immunotherapy, or radiotherapy
No other concurrent investigational agents

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00438802

Locations

United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
United States, Iowa
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, United States, 52242-1002
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

Study Chair:

Thomas E. Witzig, MD

Mayo Clinic

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

Responsible Party:	Thomas E. Witzig, M.D., Mayo Clinic
ClinicalTrials.gov Identifier:	NCT00438802 History of Changes
Other Study ID Numbers:	CDR0000530071, P50CA097274, P30CA015083, LS058C, 06-002246
Study First Received:	February 20, 2007
Last Updated:	March 24, 2011
Health Authority:	United States: Federal Government

Keywords provided by Mayo Clinic:

recurrent cutaneous T-cell non-Hodgkin lymphoma
angioimmunoblastic T-cell lymphoma
anaplastic large cell lymphoma
adult nasal type extranodal NK/T-cell lymphoma
recurrent mycosis fungoides/Sezary syndrome

Additional relevant MeSH terms:

Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders

Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Alefacept
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 12, 2012