Lymphoma
Conditions
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
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.
Interventions
DRUGlenalidomide
10 mg daily orally administered on days 1 - 21 followed by 7 days rest of a 28-day cycle, increasing dose by 5 mg every cycle, up to a maximum of 25 mg.
Sponsors
National Cancer Institute (NCI)
Northwestern University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response to Treatment | After cycle 4 of treatment (1 cycle =28 days) | In general response to treatment is defined as either complete response (CR) or partial response (PR) assessed using Composite Assessment (CA) of index lesion disease severity and is defined as the following: CR =CA ratio=0/no evidence of new disease (abnormal or pathologically positive lymph nodes, cutaneous or other tumor manifestations, visceral disease) present over 4 weeks. Patients with Sézary Syndrome must have no evidence of circulating Sézary cells (\< 5% Sézary cells=not significant). Skin biopsy is required for documentation of CR. Confirmatory CT scans are required, if baseline CTs were abnormal. PR= CA ratio ≥0.5/no new clinically abnormal lymph nodes/no progression of existing clinically abnormal lymph nodes (\<25%)/no new cutaneous tumors/no new pathologically positive lymph nodes or visceral disease in an area previously documented as-ve for at least 4 weeks. In patients with circulating Sézary cells at least a 50% reduction of malignant lymphocytes is required. |
| Progression-free Survival (PFS) | From time of treatment initiation until progression or death from any cause (up to a possible maximum of approximately 6 years) | PFS is defined from the time of treatment initiation until documentation of progressive disease or death from any cause. Progressive disease is defined as (PD) ≥25% increase in CA ratio, ≥25% increase in no. or area of clinically abnormal lymph nodes/new tumors/new pathologically positive lymph nodes/visceral disease/an increase \>25% in no. of Sézary cells. |
| Duration of Response (DOR) | From time of initial response until progressive disease (up to approximately 1 year) | DOR is defined as time of initial documentation of response to the time of documentation of progression in patients who achieve either a complete response (CR) and partial response (PR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Experience Toxicity as Assessed by NCI CTCAE v3.0 | 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 | Toxicity is defined as the number of patients who patients who experienced an adverse event that was determined to be at least possibly related to study drug and determined to be a grade 3 or higher in severity as assessed by the Common Terminology Criteria for Adverse Events v3.0 (CTCAE) where generally: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE |
Other
| Measure | Time frame |
|---|---|
| Specific Immune Effector Cell Recruitment and Augmentation of Antitumor Response at Baseline and Day 15 of Course 1 (Northwestern University Only) | After all patients have completed thru day 15 of course 1. |
| Correlation of Antiangiogenetic and Costimulatory Effects With Clinical Activity at Baseline and After Course 1 | After all patients have completed 1 course |
Countries
United States
Participant flow
Recruitment details
The study opened February 24, 2004 to accrual with the first patient being treated on study April 19 2005. the study closed to further accrual February 7, 2011 after the last patient initiated study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Lenalidomide lenalidomide: 25 mg daily orally administered on days 1 - 21 followed by 7 days rest of a 28-day cycle, or starting dose of 10mg increasing dose by 5 mg every cycle, up to a maximum of 25 mg. | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Completed 4 Cycles/Reached 1st Response | Other | 1 |
| Completed 4 Cycles/Reached 1st Response | Progressive Disease | 2 |
| Completed 4 Cycles/Reached 1st Response | Withdrawal by Subject | 2 |
| First 3 Cycles of Treatment | Adverse Event | 2 |
| First 3 Cycles of Treatment | Withdrawal by Subject | 5 |
| Follow up for a Minimum of 1 Year | Death | 6 |
Baseline characteristics
| Characteristic | Lenalidomide |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 16 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Region of Enrollment United States | 33 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 18 / 33 |
| other Total, other adverse events | 33 / 33 |
| serious Total, serious adverse events | 10 / 33 |
Outcome results
Primary
Duration of Response (DOR)
DOR is defined as time of initial documentation of response to the time of documentation of progression in patients who achieve either a complete response (CR) and partial response (PR)
Time frame: From time of initial response until progressive disease (up to approximately 1 year)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide | Duration of Response (DOR) | 10 months |
Primary
Progression-free Survival (PFS)
PFS is defined from the time of treatment initiation until documentation of progressive disease or death from any cause. Progressive disease is defined as (PD) ≥25% increase in CA ratio, ≥25% increase in no. or area of clinically abnormal lymph nodes/new tumors/new pathologically positive lymph nodes/visceral disease/an increase \>25% in no. of Sézary cells.
Time frame: From time of treatment initiation until progression or death from any cause (up to a possible maximum of approximately 6 years)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide | Progression-free Survival (PFS) | 8 months |
Primary
Response to Treatment
In general response to treatment is defined as either complete response (CR) or partial response (PR) assessed using Composite Assessment (CA) of index lesion disease severity and is defined as the following: CR =CA ratio=0/no evidence of new disease (abnormal or pathologically positive lymph nodes, cutaneous or other tumor manifestations, visceral disease) present over 4 weeks. Patients with Sézary Syndrome must have no evidence of circulating Sézary cells (\< 5% Sézary cells=not significant). Skin biopsy is required for documentation of CR. Confirmatory CT scans are required, if baseline CTs were abnormal. PR= CA ratio ≥0.5/no new clinically abnormal lymph nodes/no progression of existing clinically abnormal lymph nodes (\<25%)/no new cutaneous tumors/no new pathologically positive lymph nodes or visceral disease in an area previously documented as-ve for at least 4 weeks. In patients with circulating Sézary cells at least a 50% reduction of malignant lymphocytes is required.
Time frame: After cycle 4 of treatment (1 cycle =28 days)
Population: Patients considered not evaluable if they did not complete 1 cycle or were not evaluated for response
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lenalidomide | Response to Treatment | PR | 9 participants |
| Lenalidomide | Response to Treatment | CR | 0 participants |
Secondary
Number of Patients Who Experience Toxicity as Assessed by NCI CTCAE v3.0
Toxicity is defined as the number of patients who patients who experienced an adverse event that was determined to be at least possibly related to study drug and determined to be a grade 3 or higher in severity as assessed by the Common Terminology Criteria for Adverse Events v3.0 (CTCAE) where generally: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE
Time frame: 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lenalidomide | Number of Patients Who Experience Toxicity as Assessed by NCI CTCAE v3.0 | Fatigue (grade 3) | 7 patients |
| Lenalidomide | Number of Patients Who Experience Toxicity as Assessed by NCI CTCAE v3.0 | Infection (grade 3) | 1 patients |
| Lenalidomide | Number of Patients Who Experience Toxicity as Assessed by NCI CTCAE v3.0 | Leukopenia (grade 3) | 1 patients |
Other Pre-specified
Correlation of Antiangiogenetic and Costimulatory Effects With Clinical Activity at Baseline and After Course 1
Time frame: After all patients have completed 1 course
Other Pre-specified
Specific Immune Effector Cell Recruitment and Augmentation of Antitumor Response at Baseline and Day 15 of Course 1 (Northwestern University Only)
Time frame: After all patients have completed thru day 15 of course 1.