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

NCT ID: NCT00438802

Last Updated: 2019-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-03-31
• Study Completion Date: 2019-07-25

Brief Summary

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.

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.

Conditions

Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

alefacept

Determine both the maximum tolerated dose level as well as the optimal immunologic dose and toxicity.

Group Type: EXPERIMENTAL

Alefacept

Intervention Type: DRUG

Dose escalation theme. 0.075mg/kg by IV Weekly x 8 to 0.30mg/kg IV Weekly x 8

Interventions

Alefacept

Dose escalation theme. 0.075mg/kg by IV Weekly x 8 to 0.30mg/kg IV Weekly x 8

Intervention Type: DRUG

Other Intervention Names

Amevive

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas E. Witzig, MD

Role: STUDY_CHAIR

Mayo Clinic

Locations

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

P50CA097274

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

View Link

LS058C

Identifier Type: OTHER

Identifier Source: secondary_id

06-002246

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000530071

Identifier Type: -

Identifier Source: org_study_id