Lenalidomide in Treating Patients With Relapsed Mycosis Fungoides/Sezary Syndrome

• Sponsor: Northwestern University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00466921
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 33
• Locations: 3
• Arm: 1
• Actual Duration (Months): 96.9
• Patients Per Site: 11
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: lenalidomide	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of CC-5013 (Lenalidomide, Revlimid®) in Patients With Cutaneous T-Cell Lymphoma
• Actual Study Start Date: Apr 19, 2005
• Actual Primary Completion Date: Apr 5, 2010
• Actual Study Completion Date: May 17, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lenalidomide	Drug: lenalidomide; 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.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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 Outcome Measures

1. 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 Outcome Measures

1. 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.]

2. Correlation of Antiangiogenetic and Costimulatory Effects With Clinical Activity at Baseline and After Course 1 [After all patients have completed 1 course]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Cancer Center	Stanford	California	United States	94305-5824
2	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
3	M. D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009

Sponsors and Collaborators

• Northwestern University
• National Cancer Institute (NCI)

Investigators

• Study Chair: Timothy M. Kuzel, MD, Robert H. Lurie Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Northwestern University
• ClinicalTrials.gov Identifier: NCT00466921
• Other Study ID Numbers: NU 04H5; P30CA060553; NU-04H5
• First Posted: Apr 27, 2007
• Last Update Posted: Dec 1, 2020
• Last Verified: Oct 1, 2020

• Keywords provided by Northwestern University: 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
• Additional relevant MeSH terms: Mycoses; Lymphoma; Mycosis Fungoides; Sezary Syndrome; Lenalidomide

Study Results

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.

Arm/Group Title	Lenalidomide
Arm/Group Description	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.
Period Title: First 3 Cycles of Treatment
STARTED	33
Completed 1 Cycle	32
Started Cycle 2	31
Completed 3 Cycles	26
COMPLETED	26
NOT COMPLETED	7
Period Title: First 3 Cycles of Treatment
STARTED	26
Completed 4 Cycles/1st Response	21
COMPLETED	21
NOT COMPLETED	5
Period Title: First 3 Cycles of Treatment
STARTED	21
COMPLETED	21
NOT COMPLETED	0
Period Title: First 3 Cycles of Treatment
STARTED	33
COMPLETED	27
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Lenalidomide
Arm/Group Description	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.
Overall Participants	33
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	17 51.5%
>=65 years	16 48.5%
Sex: Female, Male (Count of Participants)
Female	18 54.5%
Male	15 45.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3%
Not Hispanic or Latino	31 93.9%
Unknown or Not Reported	1 3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	6 18.2%
White	27 81.8%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	33 100%

Outcome Measures

1. Primary Outcome

Title	Response to Treatment
Description	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)

Outcome Measure Data

Analysis Population Description

Patients considered not evaluable if they did not complete 1 cycle or were not evaluated for response

Arm/Group Title	Lenalidomide
Arm/Group Description	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.
Measure Participants	29
CR	0 0%
PR	9 27.3%

2. Primary Outcome

Title	Progression-free Survival (PFS)
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide
Arm/Group Description	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.
Measure Participants	32
Median (95% Confidence Interval) [months]	8

3. Primary Outcome

Title	Duration of Response (DOR)
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide
Arm/Group Description	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.
Measure Participants	9
Median (95% Confidence Interval) [months]	10

4. Secondary Outcome

Title	Number of Patients Who Experience Toxicity as Assessed by NCI CTCAE v3.0
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide
Arm/Group Description	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.
Measure Participants	33
Fatigue (grade 3)	7
Infection (grade 3)	1
Leukopenia (grade 3)	1

5. Other Pre-specified Outcome

Title	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Other Pre-specified Outcome

Title	Correlation of Antiangiogenetic and Costimulatory Effects With Clinical Activity at Baseline and After Course 1
Time Frame	After all patients have completed 1 course

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Arm/Group Title	Lenalidomide
Arm/Group Description	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.
All Cause Mortality
	Lenalidomide
	Affected / at Risk (%)	# Events
Total	18/33 (54.5%)
Serious Adverse Events
	Lenalidomide
	Affected / at Risk (%)	# Events
Total	10/33 (30.3%)
Blood and lymphatic system disorders
Edema	1/33 (3%)
Infections and infestations
Pneumonia	1/33 (3%)
Infection	2/33 (6.1%)
Leg infection (cellulitis)	1/33 (3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pogression of disease	1/33 (3%)
Death more than 30 days from last dose of study drug	3/33 (9.1%)
Nervous system disorders
Death dues to acute disseminated encephalomielitis	1/33 (3%)
Mental Status Changes (PVD)	1/33 (3%)
Other (Not Including Serious) Adverse Events
	Lenalidomide
	Affected / at Risk (%)	# Events
Total	33/33 (100%)
Blood and lymphatic system disorders
Hemoglobin (anemia)	14/33 (42.4%)
Neutrophils (neutropenia)	4/33 (12.1%)
Leukocytes (total WBC)	9/33 (27.3%)
Increased white blood cells	1/33 (3%)
Platelets (thrombocytopenia)	5/33 (15.2%)
Edema	5/33 (15.2%)
Edema extremities	13/33 (39.4%)
Cardiac disorders
Hypotension	2/33 (6.1%)
Endocrine disorders
Hot flashes/flushes	1/33 (3%)
Thyroid function, high (hyperthyroidism)	1/33 (3%)
hypothyroid	1/33 (3%)
Eye disorders
Visual	1/33 (3%)
Gastrointestinal disorders
Anorexia	4/33 (12.1%)
Constipation	7/33 (21.2%)
Diarrhea	9/33 (27.3%)
Heartburn/dyspepsia	2/33 (6.1%)
Nausea	4/33 (12.1%)
dry mouth	1/33 (3%)
Taste alteration(dysgeusia)	2/33 (6.1%)
Vomiting	1/33 (3%)
Dysphagia (difficulty swallowing)	1/33 (3%)
Inflammatory bowel disease	1/33 (3%)
Abdominal bloating	1/33 (3%)
General disorders
Allergic rhinitis (including sneezing,nasal stuffiness,postnasal drip)	1/33 (3%)
Fatigue	23/33 (69.7%)
Fever	1/33 (3%)
Chills	6/33 (18.2%)
Sweating	2/33 (6.1%)
Weight loss	2/33 (6.1%)
Insomnia	1/33 (3%)
Cold intolerance	1/33 (3%)
Weight gain	2/33 (6.1%)
GENERAL- Pain	12/33 (36.4%)
Infections and infestations
Lung (pneumonia)	2/33 (6.1%)
Infection (NOS)	8/33 (24.2%)
Injury, poisoning and procedural complications
fratured coccyx	1/33 (3%)
Metabolism and nutrition disorders
Alkaline phosphatase	2/33 (6.1%)
Transaminase	5/33 (15.2%)
Albumin, serum-low (hypoalbuminemia)	10/33 (30.3%)
Bilirubin (hyperbilirubinemia)	2/33 (6.1%)
Creatinine Increased	3/33 (9.1%)
Calcium, serum-low (hypocalcemia)	1/33 (3%)
Glucose, serum-high (hyperglycemia)	4/33 (12.1%)
Potassium, serum-low(hypokalemia)	1/33 (3%)
Musculoskeletal and connective tissue disorders
Muscle aches	1/33 (3%)
Muscle cramps	3/33 (9.1%)
Joint Stiffness	2/33 (6.1%)
Joint aches	1/33 (3%)
muscle weakness	1/33 (3%)
Back pain	1/33 (3%)
Pain in hands	1/33 (3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor flare - skin lesions	2/33 (6.1%)
Nervous system disorders
Neurosensory	5/33 (15.2%)
Neuromotor	1/33 (3%)
Slurred speech	1/33 (3%)
Speech impairment	1/33 (3%)
Tremor	1/33 (3%)
Ataxia	1/33 (3%)
Confusion	1/33 (3%)
Headache	1/33 (3%)
Psychiatric disorders
Dizziness	2/33 (6.1%)
Mood alteration - Depression	4/33 (12.1%)
Renal and urinary disorders
Renal insufficiency	1/33 (3%)
Respiratory, thoracic and mediastinal disorders
Cough	2/33 (6.1%)
Dyspnea (shortness of breath)	3/33 (9.1%)
Dyspnea on exertion	1/33 (3%)
Skin and subcutaneous tissue disorders
Injection site reaction/extravasation changes	1/33 (3%)
Pruritus/itching	19/33 (57.6%)
erythoderma	3/33 (9.1%)
Rash	4/33 (12.1%)
Burning	3/33 (9.1%)
Skin peeling	3/33 (9.1%)
Dry skin	1/33 (3%)
Scaling	1/33 (3%)
Alopecia	2/33 (6.1%)
Skin ulcer	1/33 (3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.