Clinical trial NCT01724177: A Phase 2 Study of Lenalidomide in Patients With Relapsed or Recurrent Adult T-cell Leukemia-lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adult T-Cell Leukemia-Lymphoma
Keywords: Lenalidomide
ATL
ATLL
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2012-11-09
Enrollment: 26
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Who Achieved a Complete Response, Unconfirmed Complete Response, or Partial Response as Assessed by the Efficacy-Safety Evaluation Committee (ESEC)
timeFrame: 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 outcomes:
measure: Kaplan Meier Estimate of Progression Free Survival (PFS) as Assessed by the ESEC
timeFrame: 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
measure: Kaplan-Meier Estimate of Time to Progression (TTP)
timeFrame: 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
measure: Number of Participants With Treatment Emergent Adverse Events
timeFrame: 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
measure: Kaplan-Meier Estimate of Duration of Response (DOR) for Responders as Assessed by the ESEC
timeFrame: 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
measure: Percentage of Participants Who Achieved a Complete Response, Unconfirmed Complete Response (CRu), Partial Response or Stable Disease (SD) as Assessed by the ESEC
timeFrame: 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
measure: Kaplan-Meier Estimate for Overall Survival
timeFrame: 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
Other outcomes:
measure: Time to Response
timeFrame: 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
Locations:
city: Nagoya
country: Japan
facility: Nagoya City University Hospital
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Toon
country: Japan
facility: Ehime University Hospital
state: Ehime
city: Morioka
country: Japan
facility: Iwate Medical University Hospital
state: Iwate
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Sasebo
country: Japan
facility: Sasebo City General Hospital
state: Nagasaki
city: Nakagami
country: Japan
facility: Heart Life Hospital
state: Okinawa
city: Izumo
country: Japan
facility: Shimane University Hospital
state: Shimane
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Kagoshima
country: Japan
facility: Imamura Bunin Hospital
city: Kagoshima
country: Japan
facility: Kagoshima University Medical and Dental Hospital
city: Kagoshima
country: Japan
facility: National Hospital Organization Kagoshima Medical Center
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Nagasaki
country: Japan
facility: Nagasaki University Hospital
city: Nagasaki
country: Japan
facility: The Japanese Red Cross Nagasaki Genbaku Hospital
city: Oita
country: Japan
facility: Oita Prefectual Hospital
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
Study officials:
affiliation: Celgene K.K.
name: Toru Sasaki
role: STUDY_DIRECTOR
References:
citation: Ishida T, Fujiwara H, Nosaka K, Taira N, Abe Y, Imaizumi Y, Moriuchi Y, Jo T, Ishizawa K, Tobinai K, Tsukasaki K, Ito S, Yoshimitsu M, Otsuka M, Ogura M, Midorikawa S, Ruiz W, Ohtsu T. Multicenter Phase II Study of Lenalidomide in Relapsed or Recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002. J Clin Oncol. 2016 Dec;34(34):4086-4093. doi: 10.1200/JCO.2016.67.7732. Epub 2016 Sep 30.