Clinical trial NCT00438802: Alefacept in Treating Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma or Peripheral T-Cell Non-Hodgkin's Lymphoma
Official title: A Phase I Study of Alefacept (AmeviveTM) in the Treatment of Cutaneous T-cell Lymphoma and Peripheral T-cell NHL
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma
Keywords: 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
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-02-22
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Dose Limiting Toxicity (DLT)
timeFrame: 8 weeks from registration
measure: Maximum Tolerated Dose (MTD)
timeFrame: 8 weeks from registration
Secondary outcomes:
measure: Clinical Response
timeFrame: up to 12 cycles (28 days per cycle) of treatment.
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Thomas E. Witzig, MD
role: STUDY_CHAIR
References: