Clinical trial NCT00466921: Lenalidomide in Treating Patients With Relapsed Mycosis Fungoides/Sezary Syndrome
Official title: Phase II Trial of CC-5013 (Lenalidomide, Revlimid®) in Patients With Cutaneous T-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: recurrent mycosis fungoides/Sezary syndrome
stage I mycosis fungoides/Sezary syndrome
stage II mycosis fungoides/Sezary syndrome
stage III mycosis fungoides/Sezary syndrome
stage IV mycosis fungoides/Sezary syndrome
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-04-27
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Lenalidomide may stop the growth of mycosis fungoides/Sezary syndrome by blocking blood flow to the cancer.

PURPOSE: This phase II trial is studying how well lenalidomide works in treating patients with relapsed mycosis fungoides/Sezary syndrome.

Detailed description: OBJECTIVES:

Primary

* Determine the response rate and duration of response in patients with relapsed mycosis fungoides/Sézary syndrome treated with lenalidomide.
* Determine the progression-free survival of patients treated with this drug.

Secondary

* Determine the toxicity of this drug in these patients.
* Correlate the antiangiogenetic and costimulatory effects of this drug with clinical activity in skin biopsies from these patients.
* Assess the specific immune effector cell recruitment and augmentation of antitumor response in these patients. (Northwestern University only)

OUTLINE: This is a multicenter study.

Patients receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 2 courses. Patients with progressive disease are removed from study. Patients achieving complete response receive 2 additional courses of treatment beyond complete response. Patients achieving partial response or stable disease may continue to receive lenalidomide as above for up to 2 years. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients undergo tissue biopsies at baseline and on day 1 of course 2. Tissue specimens are analyzed for vessel density, presence of adhesion molecules, and immunophenotyping of dermal infiltrate.\*

NOTE: \*At Northwestern University only, blood and tissue samples from 5-10 patients are collected. Peripheral blood samples are analyzed for immune cell repertoire (CD4+, CD8+ T cells, NK cells, NKT cells, CD4+, CD25+ T-regulatory cells, monocytes, and dendritic cell subsets), cell surface molecules, and for TH1/TH2-associated cytokines, such as interleukin (IL)-2, IL-4, IL-10, IL-12, interferon gamma, and tumor necrosis factor alpha, by flow cytometry at baseline, day 15 of course 1, and at the end of course 1. Immunological activation is assessed by analyzing surface expression of CD45RO and CTLA-4 on CD4+ and CD8+ T cells in blood and skin samples. Skin specimens are stored for future research studies on predictive markers of lenalidomide activity.

After completion of study treatment, patients are followed every 3 months for 1 year.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed mycosis fungoides/Sézary syndrome

  * Stage IA-IVB disease
* Must have failed ≥ 1 prior topical treatment, including any of the following:

  * Steroids
  * Nitrogen mustard
  * Retinoids
  * Phototherapy
  * Photochemotherapy
  * Radiotherapy
  * Total skin electron beam
* Measurable disease with ≥ 1 indicator lesion designated prior to study entry

  * Erythrodermic patients are eligible

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* WBC ≥ 3,000/mm³
* ANC ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Creatinine ≤ 2.0 mg/dL
* Bilirubin ≤ 2.2 mg/dL
* AST and ALT ≤ 2 times upper limit of normal
* Not pregnant or nursing
* Negative pregnancy test
* Fertile women must use effective double-method contraception for ≥ 4 weeks before, during, and for ≥ 4 weeks after completion of study therapy
* Fertile men must use effective contraception during and for ≥ 4 weeks after completion of study therapy
* No other malignancy within the past 5 years except treated squamous cell and basal cell carcinoma of the skin, carcinoma in situ of the cervix, or surgically removed melanoma in situ of the skin (stage 0), with histologically confirmed free margins of excision and no current evidence of disease
* No acute infection requiring systemic treatment
* No known allergic reaction or hypersensitivity to thalidomide

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* More than 4 weeks since prior topical therapy, systemic chemotherapy, or biological therapy
* No prior stem cell transplantation
* No other concurrent systemic antipsoriatic or anticancer therapies, including radiotherapy, thalidomide, or other investigational agents
* No other concurrent topical agents except emollients

Primary outcomes:
measure: Response to Treatment
timeFrame: After cycle 4 of treatment (1 cycle =28 days)
measure: Progression-free Survival (PFS)
timeFrame: From time of treatment initiation until progression or death from any cause (up to a possible maximum of approximately 6 years)
measure: Duration of Response (DOR)
timeFrame: From time of initial response until progressive disease (up to approximately 1 year)
Secondary outcomes:
measure: Number of Patients Who Experience Toxicity as Assessed by NCI CTCAE v3.0
timeFrame: From treatment initiation until up to 30 days post treatment with possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of treatment permitted if meeting response criteria
Other outcomes:
measure: Specific Immune Effector Cell Recruitment and Augmentation of Antitumor Response at Baseline and Day 15 of Course 1 (Northwestern University Only)
timeFrame: After all patients have completed thru day 15 of course 1.
measure: Correlation of Antiangiogenetic and Costimulatory Effects With Clinical Activity at Baseline and After Course 1
timeFrame: After all patients have completed 1 course
Locations:
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
Study officials:
affiliation: Robert H. Lurie Cancer Center
name: Timothy M. Kuzel, MD
role: STUDY_CHAIR
References:
citation: Querfeld C, Rosen ST, Guitart J, Duvic M, Kim YH, Dusza SW, Kuzel TM. Results of an open-label multicenter phase 2 trial of lenalidomide monotherapy in refractory mycosis fungoides and Sezary syndrome. Blood. 2014 Feb 20;123(8):1159-66. doi: 10.1182/blood-2013-09-525915. Epub 2013 Dec 11.