Alefacept in Treating Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma or Peripheral T-Cell Non-Hodgkin's Lymphoma
|ClinicalTrials.gov Identifier: NCT00438802|
Recruitment Status : Completed
First Posted : February 22, 2007
Results First Posted : October 2, 2017
Last Update Posted : October 2, 2017
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 or disease||Intervention/treatment||Phase|
|Lymphoma||Drug: Alefacept||Phase 1|
- 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.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||23 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Alefacept (AmeviveTM) in the Treatment of Cutaneous T-cell Lymphoma and Peripheral T-cell NHL|
|Study Start Date :||March 2006|
|Primary Completion Date :||July 2010|
|Study Completion Date :||March 2016|
Determine both the maximum tolerated dose level as well as the optimal immunologic dose and toxicity.
Dose escalation theme. 0.075mg/kg by IV Weekly x 8 to 0.30mg/kg IV Weekly x 8
Other Name: Amevive
- 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.
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.
- 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.
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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00438802
|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|
|Study Chair:||Thomas E. Witzig, MD||Mayo Clinic|