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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00438802
First Posted: February 22, 2007
Last Update Posted: October 2, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic
February 20, 2007
February 22, 2007
September 12, 2016
October 2, 2017
October 2, 2017
March 2006
July 2010   (Final data collection date for primary outcome measure)
  • Dose Limiting Toxicity (DLT) [ Time Frame: 8 weeks from registration ]

    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.

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    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.

  • Maximum Tolerated Dose (MTD) [ Time Frame: 8 weeks from registration ]
    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.
  • Tolerability
  • Immunostimulation
Complete list of historical versions of study NCT00438802 on ClinicalTrials.gov Archive Site
Clinical Response [ Time Frame: up to 12 cycles (28 days per cycle) of treatment. ]

Treatment response and evaluation will be performed using standardized lymphoma International Working Group recommendations.

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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.
Clinical Response
Not Provided
Not Provided
 
Alefacept in Treating Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma or Peripheral T-Cell Non-Hodgkin's Lymphoma
A Phase I Study of Alefacept (AmeviveTM) in the Treatment of Cutaneous T-cell Lymphoma and Peripheral T-cell NHL

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.

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.

Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Lymphoma
Drug: Alefacept
Dose escalation theme. 0.075mg/kg by IV Weekly x 8 to 0.30mg/kg IV Weekly x 8
Other Name: Amevive
Experimental: alefacept
Determine both the maximum tolerated dose level as well as the optimal immunologic dose and toxicity.
Intervention: Drug: Alefacept
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
23
March 2016
July 2010   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 120 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00438802
CDR0000530071
P50CA097274 ( U.S. NIH Grant/Contract )
P30CA015083 ( U.S. NIH Grant/Contract )
LS058C ( Other Identifier: Mayo Clinic Cancer Center )
06-002246 ( Other Identifier: Mayo Clinic IRB )
Yes
Not Provided
Not Provided
Mayo Clinic
Mayo Clinic
National Cancer Institute (NCI)
Study Chair: Thomas E. Witzig, MD Mayo Clinic
Mayo Clinic
March 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP