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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
  Purpose

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.


Condition Intervention Phase
Lymphoma Drug: Alefacept Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of Alefacept (AmeviveTM) in the Treatment of Cutaneous T-cell Lymphoma and Peripheral T-cell NHL

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 23
Study Start Date: March 2006
Study Completion Date: March 2016
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: alefacept
Determine both the maximum tolerated dose level as well as the optimal immunologic dose and toxicity.
Drug: Alefacept
Dose escalation theme. 0.075mg/kg by IV Weekly x 8 to 0.30mg/kg IV Weekly x 8
Other Name: Amevive

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00438802


Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
United States, Iowa
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, United States, 52242-1002
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
Study Chair: Thomas E. Witzig, MD Mayo Clinic
  More Information

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT00438802     History of Changes
Other Study ID Numbers: 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 )
First Submitted: February 20, 2007
First Posted: February 22, 2007
Results First Submitted: September 12, 2016
Results First Posted: October 2, 2017
Last Update Posted: October 2, 2017
Last Verified: March 2016

Keywords provided by Mayo Clinic:
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

Additional relevant MeSH terms:
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Alefacept
Dermatologic Agents