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

Primary Purpose

Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Alefacept
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring 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

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • City of Hope Comprehensive Cancer Center
  • Holden Comprehensive Cancer Center at University of Iowa
  • Mayo Clinic Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

alefacept

Arm Description

Determine both the maximum tolerated dose level as well as the optimal immunologic dose and toxicity.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.

Full Information

First Posted
February 20, 2007
Last Updated
July 31, 2019
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00438802
Brief Title
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

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
March 2006 (Actual)
Primary Completion Date
August 24, 2010 (Actual)
Study Completion Date
July 25, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
alefacept
Arm Type
Experimental
Arm Description
Determine both the maximum tolerated dose level as well as the optimal immunologic dose and toxicity.
Intervention Type
Drug
Intervention Name(s)
Alefacept
Other Intervention Name(s)
Amevive
Intervention Description
Dose escalation theme. 0.075mg/kg by IV Weekly x 8 to 0.30mg/kg IV Weekly x 8
Primary Outcome Measure Information:
Title
Dose Limiting Toxicity (DLT)
Description
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.
Time Frame
8 weeks from registration
Title
Maximum Tolerated Dose (MTD)
Description
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.
Time Frame
8 weeks from registration
Secondary Outcome Measure Information:
Title
Clinical Response
Description
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.
Time Frame
up to 12 cycles (28 days per cycle) of treatment.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas E. Witzig, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Study Chair
Facility Information:
Facility Name
City of Hope Comprehensive Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010-3000
Country
United States
Facility Name
Holden Comprehensive Cancer Center at University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242-1002
Country
United States
Facility Name
Mayo Clinic Cancer Center
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

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

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