A Phase I Study of Alefacept (AmeviveTM) in the Treatment of Cutaneous T-cell Lymphoma and Peripheral T-cell NHL
18 Years
N/A
Both
Lymphoma
Trial Information
A Phase I Study of Alefacept (AmeviveTM) in the Treatment of Cutaneous T-cell Lymphoma and Peripheral T-cell NHL
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.
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
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Tolerability
Outcome Time Frame:
9/21/2006 - 7/06/2010
Safety Issue:
Yes
Principal Investigator
Thomas E. Witzig, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Federal Government
Study ID:
CDR0000530071
NCT ID:
NCT00438802
Start Date:
March 2006
Completion Date:
May 2013
Related Keywords:
- Lymphoma
- 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
- Lymphoma
- Lymphoma, Non-Hodgkin
- Lymphoma, T-Cell
- Lymphoma, T-Cell, Cutaneous
Name | Location |
|---|---|
| Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
| Holden Comprehensive Cancer Center at University of Iowa | Iowa City, Iowa 52242-1002 |
| City of Hope Comprehensive Cancer Center | Duarte, California 91010 |
