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

Mayo Clinic

Status and phase

Completed

Phase 1

Conditions

Lymphoma

Treatments

Drug: Alefacept

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00438802

06-002246 (Other Identifier)

P30CA015083 (U.S. NIH Grant/Contract)

CDR0000530071

LS058C (Other Identifier)

P50CA097274 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment

23 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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