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

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ClinicalTrials.gov Identifier: NCT01724177
Recruitment Status : Completed
First Posted : November 9, 2012
Results First Posted : January 5, 2016
Last Update Posted : May 28, 2018
Sponsor:
Information provided by (Responsible Party):
Celgene

Tracking Information
First Submitted Date  ICMJE November 7, 2012
First Posted Date  ICMJE November 9, 2012
Results First Submitted Date  ICMJE September 4, 2015
Results First Posted Date  ICMJE January 5, 2016
Last Update Posted Date May 28, 2018
Actual Study Start Date  ICMJE November 12, 2012
Actual Primary Completion Date November 20, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 18, 2018)
Percentage of Participants Who Achieved a Complete Response, Unconfirmed Complete Response, or Partial Response as Assessed by the Efficacy-Safety Evaluation Committee (ESEC) [ Time Frame: 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
Original Primary Outcome Measures  ICMJE
 (submitted: November 7, 2012)
Overall Response Rate [ Time Frame: Up to 3 years ]
The primary endpoint is the overall response rate (Complete Response + Complete Response unconfirmed + Partial Response). The response to lenalidomide will be evaluated according to the criteria proposed at the International Consensus Meeting
Change History Complete list of historical versions of study NCT01724177 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2018)
  • Kaplan Meier Estimate of Progression Free Survival (PFS) as Assessed by the ESEC [ Time Frame: 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.
  • Kaplan-Meier Estimate of Time to Progression (TTP) [ Time Frame: 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
  • Number of Participants With Treatment Emergent Adverse Events [ Time Frame: 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.
  • Kaplan-Meier Estimate of Duration of Response (DOR) for Responders as Assessed by the ESEC [ Time Frame: 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.
  • Percentage of Participants Who Achieved a Complete Response, Unconfirmed Complete Response (CRu), Partial Response or Stable Disease (SD) as Assessed by the ESEC [ Time Frame: 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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 7, 2012)
  • Progression Free Survival [ Time Frame: Up to 3 years ]
    Time To Progression calculated as the time from the start of study treatment to the first documented progression.
  • Time to progression [ Time Frame: Up to 3 years ]
    Time To Progression calculated as the time from the start of study treatment to the first documented progression.
  • Adverse Events [ Time Frame: Up to 3 years ]
    Number of patients with adverse events
  • Duration of Response [ Time Frame: Up to 3 years ]
    The response duration in patients with objective responses will be 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.
  • Tumor Control Rate [ Time Frame: Up to 3 years ]
    The disease control ratio (Stable Disease or Partial Response or Complete Response unconfirmed or Complete Response)
  • Overall Survival [ Time Frame: Up to 3 years ]
    Overall Survival calculated as the time from the start of study treatment to the death due to any cause
Current Other Pre-specified Outcome Measures
 (submitted: March 18, 2018)
Time to Response [ Time Frame: 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 ]
Time to Response was defined as the time from the first dose of study treatment to the initial documented response (CR or CRu, or PR)
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 2 Study of Lenalidomide in Patients With Relapsed or Recurrent Adult T-cell Leukemia-lymphoma
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Adult T-Cell Leukemia-Lymphoma
Intervention  ICMJE Drug: Lenalidomide
25 mg of Lenalidomide administered orally once daily
Other Name: Revlimid
Study Arms  ICMJE Experimental: Lenalidomide
Lenalidomide 25mg by mouth (PO) daily until progressive disease or unacceptable toxicity
Intervention: Drug: Lenalidomide
Publications * 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. Epub 2016 Sep 30.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 26, 2015)
26
Original Estimated Enrollment  ICMJE
 (submitted: November 7, 2012)
25
Actual Study Completion Date  ICMJE March 21, 2017
Actual Primary Completion Date November 20, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01724177
Other Study ID Numbers  ICMJE CC-5013-ATLL-002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Celgene
Study Sponsor  ICMJE Celgene
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Toru Sasaki Celgene K.K.
PRS Account Celgene
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP