A Phase 2 Study of Lenalidomide in Patients With Relapsed or Recurrent Adult T-cell Leukemia-lymphoma

Study Overview
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Brief Summary
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To evaluate the efficacy of lenalidomide in patients with Adult T-cell Leukemia-lymphoma (ATL) who have previously received chemotherapy for ATL.

Official Title
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A Phase 2, Multicenter, Single-arm, Open-label Study to Evaluate the Safety and Efficacy of Lenalidomide in Patients With Relapsed or Recurrent Adult T-cell Leukemia-lymphoma

Conditions
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Adult T-Cell Leukemia-Lymphoma

Intervention / Treatment
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* Drug: Lenalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must understand and voluntarily sign the informed consent Aged 20 years or older (at the time of signing the informed consent) Have a documented diagnosis of either: acute-, lymphoma-, or unfavorable chronic-type adult T-cell leukemia-lymphoma Have received ≥1 prior anti-adult T-cell leukemia-lymphoma therapy, have achieved stable disease or better on their immediately prior therapy and have relapsed or progressed at the time of obtaining signed informed consent Subjects for whom at least 1 measurable lesion (measurable lesion of computed tomography scan, peripheral blood or skin lesion) is confirmed in the lesion assessment before registration Have an Eastern Cooperative Oncology Group performance status of 0 to 2 at registration Must be able to adhere to the study visit schedule and other protocol requirements Must agree to comply to Lenalidomide Pregnancy Prevention Risk Management Plan Exclusion Criteria: Have a history of central nervous system involvement or present with central nervous system symptoms, and are diagnosed with central nervous system lymphoma by cerebrospinal fluid cytology examination, head computed tomography scan or brain magnetic resonance imaging during the screening Are pregnant or lactating Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study. Examples of such medical condition are, but are not limited to, as follows: Uncontrolled diabetes mellitus as defined by the investigator or sub-investigator Chronic congestive heart failure (New York Heart Association Class III or IV) Unstable angina pectoris, angioplasty, stenting, or myocardial infarction (within 6 months before starting the study drug) Clinically significant cardiac arrhythmia that is symptomatic or requires treatment, or asymptomatic sustained ventricular tachycardia (subjects with controlled atrial fibrillation that is asymptomatic are eligible for this study) Major surgery within 28 days of the start of study treatment Exhibit grade 4 neurological disorders Patients who are at a high risk for a thromboembolic event and are not willing to take venous thromboembolic prophylaxis. Develop active tuberculous disease, herpes simplex, systemic mycosis, or other active infections requiring systemic administration of antibiotics, antiviral agents, or antifungal drugs Known human immunodeficiency virus positivity Have hepatitis B surface antigen-positive, or hepatitis C virus anti-body positive. In case hepatitis B core antibody and/or hepatitis B surface antibody is positive even if hepatitis B surface antigen-negative, a hepatitis B virus deoxyribonucleic acid test should be performed and if positive the subject will be excluded Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study Have a history of allogenic stem cell transplantation Have received autologous stem cell transplantation within 12 weeks (84 days) of the start of study treatment Have previously used lenalidomide Have a history of desquamating (blistering) rash while taking thalidomide Have received any investigational drugs (unapproved drugs in Japan) within 4 weeks (28 days) of the start of study medication Have received any antibody agents within 12 weeks (84 days) of the start of study medication Have received chemotherapeutic agents or immunomodulatory drugs for the treatment of adult T-cell leukemia-lymphoma within 4 weeks (28 days) of the start of study treatment Have received radiotherapy within 4 weeks (28 days) of the start of study treatment Have a history or complication of another malignant tumor other than adult T-cell leukemia-lymphoma and the following malignant tumors, unless the patients have been free of the disease for 5 years or longer Basal cell carcinoma of the skin Squamous cell carcinoma of the skin Cervical carcinoma in situ Carcinoma in situ of the breast An incidental histological finding of prostate carcinoma (TNM stage T1a or T1b) Early-stage gastric cancer treated with endoscopic mucosal resection or endoscopic submucosal dissection Have had any of the following abnormal measurements at screening performed within 1 week (7 days) prior to the registration; Neutrophil count: < 1,200/µL Platelet count: < 75,000/µL Serum aspartate aminotransferase/glutamyl oxaloacetic transaminase or alanine aminotransferase/glutamyl pyruvic transaminase: > 3 times the upper limit of normal Bilirubin level: > 1.5 times the upper limit of normal Creatinine clearance: < 60 mL/min Any condition that confounds the ability to interpret data from the study.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lenalidomide<br>Lenalidomide 25mg by mouth (PO) daily until progressive disease or unacceptable toxicity | Drug: Lenalidomide<br>* 25 mg of Lenalidomide administered orally once daily<br>* Other names: Revlimid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved a Complete Response, Unconfirmed Complete Response, or Partial Response as Assessed by the Efficacy-Safety Evaluation Committee (ESEC) | ORR is a Complete Response (CR) + Complete Response unconfirmed (CRu) + Partial Response (PR). A CR requires that target lesions have regressed to normal; nodal non-target lesions have regressed to normal; extranodal non-target lesions have disappeared; hepatomegaly/splenomegaly has disappeared; skin findings are GR 0; peripheral blood is normal; Bone marrow (BM) infiltration is negative and no new lesions. A CRu requires the sum of the product diameters (SPD) of target lesions have decreased by at least 75% from baseline; nodal non-target lesions have regressed to normal size; extranodal non-target lesions have disappeared; hepatomegaly/splenomegaly has disappeared; skin findings are Grade 0; peripheral blood is normal; BM infiltration is negative and no new lesions. A PR requires the SPD of target lesions has decreased by at least 50% from baseline; all nodal non-target lesions have regressed to normal or show no increase in size; all extranodal non-target lesions have disappeared | From day 1 of study treatment to date of first documented CR, CRU or PR; Up to data cut-off date of 19 May 2017; maximum study duration was 134.1 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kaplan Meier Estimate of Progression Free Survival (PFS) as Assessed by the ESEC | PFS was defined as the time from the first dose of study treatment to progressive disease (PD) or death due to any cause on study or within 28 days after study discontinuation, whichever occurred earlier. | From day 1 of study treatment to the date of disease progression; up to data cut date of date of 19 May 2017; maximum study duration was 134.1 weeks | 
| Kaplan-Meier Estimate of Time to Progression (TTP) | Time to progression was calculated as the time from the first dosing of study treatment to the first documented PD and assessed by the ESEC | From day 1 of study treatment to the date of disease progression; up to data cut date of 19 May 2017; maximum study duration was 134.1 weeks | 
| Number of Participants With Treatment Emergent Adverse Events | Treatment Emergent Adverse Event (TEAE) was defined as any AE occurring on or after the start of study treatment and within 28 days after the last dose. Severity was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0): Grade 1= Mild Grade 2= Moderate Grade 3= Severe Grade 4= Life-threatening and Grade 5= Death related to AE. Serious AEs (SAEs) were those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above. | From the date of the first dose of study drug up to 28 days after the last dose of study drug; up to data cutoff date of 19 May 2017; maximum treatment duration was 130.1 weeks | 
| Kaplan-Meier Estimate of Duration of Response (DOR) for Responders as Assessed by the ESEC | The response duration in participants with an objective response was measured from the date of the first Complete Response or Complete Response unconfirmed or Partial Response to the first date of Relapsed Disease or Progressive Disease (PD). For participants who did not progress during the study, DOR was censored at the last adequate response assessment not showing evidence of PD. | From day 1 of study treatment to first documented response; up to data cut-off date of 19 May 2017; Maximum study duration was 134.1 Weeks | 
| Percentage of Participants Who Achieved a Complete Response, Unconfirmed Complete Response (CRu), Partial Response or Stable Disease (SD) as Assessed by the ESEC | The tumor control rate was measured for those with a response of Complete Remission, + CRu, + PR + Stable Disease (SD) in the EE population based on the best response. | From day 1 of study treatment to first documented response; up to data cut-off date of 19 May 2017; maximum study duration was 134.1 weeks | 
| Kaplan-Meier Estimate for Overall Survival | Overall Survival was defined as the time from the start of study treatment to the death due to any cause. For participants who were still alive at the time of the data cutoff, survival data were censored at the latest available date the participant was known to be alive. | From Day 1 of study treatment to disease progression or death; up to final data cut-off date of 19 May 2017; maximum surivival time was 197.9 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lenalidomide, ATL, ATLL