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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase I Study of Alefacept (AmeviveTM) in the Treatment of Cutaneous T-cell Lymphoma and Peripheral T-cell NHL

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: Alefacept


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: alefacept<br>Determine both the maximum tolerated dose level as well as the optimal immunologic dose and toxicity. | Drug: Alefacept<br>* Dose escalation theme. 0.075mg/kg by IV Weekly x 8 to 0.30mg/kg IV Weekly x 8<br>* Other names: Amevive;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicity (DLT) | The Maximum Tolerated Dose (MTD) will be defined as the highest safely-tolerated dose where at most one out of six patients experiences a Dose Limiting Toxicity (DLT) with the next higher dose level having at least 2 patients who have experienced DLT. The MTD determination will be based on toxicities encountered during the first 8 weeks of treatment.> > For this protocol, dose-limiting toxicity (DLT) will be defined as an adverse event attributed (definitely, probably, or possibly) to the study treatment and meeting the following criteria:> grade 4 toxicity for neutrophils (<0.5 x 109/L) or platelets (<25 x 109/L)> any grade 3 or higher solid organ toxicity not explainable by another obvious cause.> more than 10 x ULN AST toxicity for more than 14 days> any grade 4 infection.> The number of patients who reported a dose limiting toxicity is reported here. | 8 weeks from registration | 
| Maximum Tolerated Dose (MTD) | The Maximum Tolerated Dose (MTD) will be defined as the highest safely-tolerated dose where at most one out of six patients experiences a Dose Limiting Toxicity (DLT) with the next higher dose level having at least 2 patients who have experienced DLT. The MTD determination will be based on DLT toxicities encountered during the first 8 weeks of treatment reported in Primary Outcome Measure #1. | 8 weeks from registration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response | Treatment response and evaluation will be performed using standardized lymphoma International Working Group recommendations.> > A Complete Response (CR) requires:> Complete disappearance of all detectable clinical and radiographic evidence of> disease.> All lymph nodes and nodal masses must have regressed to normal size.> Partial Response (PR):> greater than 50% decrease in Sum of Product Dimensions of the six largest dominant nodes, nodal masses, or skin lesions.> No increase in size of other nodes> no new sites of disease. | up to 12 cycles (28 days per cycle) of treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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