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

Phase 2

Completed

Conditions: Adult T-Cell Leukemia-Lymphoma

Interventions: Drug: Lenalidomide

Registration Number: NCT01724177

Lead Sponsor: Celgene

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 26

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Lenalidomide	Lenalidomide	Lenalidomide 25mg by mouth (PO) daily until progressive disease or unacceptable toxicity

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved a Complete Response, Unconfirmed Complete Response, or Partial Response as Assessed by the Efficacy-Safety Evaluation Committee (ESEC)	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	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

Secondary Outcome Measures

Name	Time	Method
Kaplan Meier Estimate of Progression Free Survival (PFS) as Assessed by the ESEC	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	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.
Number of Participants With Treatment Emergent Adverse Events	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	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.
Percentage of Participants Who Achieved a Complete Response, Unconfirmed Complete Response (CRu), Partial Response or Stable Disease (SD) as Assessed by the ESEC	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	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.
Kaplan-Meier Estimate for Overall Survival	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	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.
Kaplan-Meier Estimate of Time to Progression (TTP)	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	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
Kaplan-Meier Estimate of Duration of Response (DOR) for Responders as Assessed by the ESEC	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	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.

Trial Locations

Locations (18): National Cancer Center Hospital East
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Kashiwa, Chiba, Japan
Kumamoto University Hospital
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Kumamoto, Japan
Kagoshima University Medical and Dental Hospital
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Kagoshima, Japan
Sasebo City General Hospital
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Sasebo, Nagasaki, Japan
Ehime University Hospital
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Toon, Ehime, Japan
Heart Life Hospital
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Nakagami, Okinawa, Japan
Shimane University Hospital
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Izumo, Shimane, Japan
Imamura Bunin Hospital
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Kagoshima, Japan
National Hospital Organization Kagoshima Medical Center
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Kagoshima, Japan
Nagasaki University Hospital
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Nagasaki, Japan
Oita Prefectual Hospital
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Oita, Japan
National Cancer Center Hospital
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Tokyo, Japan
The Japanese Red Cross Nagasaki Genbaku Hospital
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Nagasaki, Japan
Iwate Medical University Hospital
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Morioka, Iwate, Japan
National Hospital Organization Kyushu Cancer Center
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Fukuoka, Japan
Nagoya City University Hospital
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Nagoya, Aichi, Japan
Kyushu University Hospital
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Fukuoka, Japan
Tohoku University Hospital
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Sendai, Miyagi, Japan