Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Biomarker/Laboratory analysis, Treatment	Active	18 and over	NCI	MAYO-LS058C MAYO-06-002246, NCT00438802

Special Category: SPORE trial

Objectives

Primary

1. 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

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

Entry 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

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

Patient Characteristics:

• ECOG performance status 0-2
• Absolute neutrophil count ≥ 1,000/mm³
• Platelet count ≥ 75,000/mm³
• 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

Expected Enrollment

A total of 24 patients will be accrued for this study.

Outcomes

Tolerability
Immunostimulation

Clinical response

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.

Trial Contact Information

Trial Lead Organizations

Mayo Clinic Cancer Center

Thomas Witzig, MD, Protocol chair		Ph: 507-538-7623 Email: cancerclinicaltrials@mayo.edu
Mark Pittelkow, MD, Protocol co-chair		Ph: 507-538-7623 Email: cancerclinicaltrials@mayo.edu
Brian Link, MD, Protocol co-chair		Ph: 319-353-8504 Email: brian-link@uiowa.edu
Yvette Kasamon, MD, Protocol co-chair		Ph: 410-955-8839 Email: ykasamo1@jhmi.edu
Jasmine Zain, MD, Protocol co-chair		Ph: 800-826-4673 Email: becomingapatient@coh.org

U.S.A.
California
	Duarte
	City of Hope Comprehensive Cancer Center
		Clinical Trials Office - City of Hope Comprehensive Cancer Center	Ph:  800-826-4673
			Email: becomingapatient@coh.org
Iowa
	Iowa City
	Holden Comprehensive Cancer Center at University of Iowa
		Cancer Information Service	Ph:  800-237-1225
Minnesota
	Rochester
	Mayo Clinic Cancer Center
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623

Registry Information
Official Title		A Phase I Study of Alefacept (AmeviveTM) in the Treatment of Cutaneous T-cell Lymphoma and Peripheral T-cell NHL
Trial Start Date		2006-03-13
Trial Completion Date		2009-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00438802
Date Submitted to PDQ		2007-01-04
Information Last Verified		2009-02-17
NCI Grant/Contract Number		CA097274, CA15083