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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene ( Celgene Corporation )
ClinicalTrials.gov Identifier:
NCT01724177
First received: November 7, 2012
Last updated: November 26, 2015
Last verified: November 2015
  Purpose
To evaluate the efficacy of lenalidomide in patients with Adult T-cell Leukemia-lymphoma (ATL) who have previously received chemotherapy for ATL.

Condition Intervention Phase
Adult T-Cell Leukemia-Lymphoma
Drug: Lenalidomide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Celgene:

Primary Outcome Measures:
  • Overall Response Rate (ORR) Based on the Adult T-cell Leukemia-lymphoma (ATLL) Response Criteria and Assessed by the Efficacy-Safety Evaluation Committee (ESEC) [ Time Frame: Up to the data cut-off of 20 November 2014; maximum time on study treatment was 79.7 weeks ] [ Designated as safety issue: No ]
    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:
  • Kaplan Meier Estimate of Progression Free Survival (PFS) Assessed by ESEC [ Time Frame: Up to the cut-off date of 20 November 2014; maximum time on study treatment was 79.7 weeks ] [ Designated as safety issue: No ]
    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: Up to data cut-off of 20 November 2014; maximum time on study treatment was 79.7 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to data cut-off of 20 Nov 2014; maximum time on study treatment was 79.7 weeks ] [ Designated as safety issue: No ]
    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 Had a Achieved a CR, CRu, PR or Stable Disease (SD) as Assessed by the ESEC [ Time Frame: Up to the data cut-off of 20 November 2014; maximum time on study treatment was 79.7 weeks ] [ Designated as safety issue: No ]
    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 responses.

  • Kaplan-Meier Estimate for Overall Survival [ Time Frame: Up to the data cut-off date of 20 November 2014; maximum time on study treatment was 79.7 weeks ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Adverse Events [ Time Frame: Up to data cutoff of 20 November 2014; maximum time on study treatment was 79.7 weeks ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 26
Study Start Date: November 2012
Estimated Study Completion Date: December 2017
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenalidomide
Lenalidomide 25mg by mouth (PO) daily until progressive disease or unacceptable toxicity
Drug: Lenalidomide
25 mg of Lenalidomide administered orally once daily
Other Name: Revlimid

  Eligibility

Ages Eligible for Study:   20 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01724177

Locations
Japan
Nagoya City University Hospital
Nagoya, Aichi, Japan, 467-8602
National Cancer Center Hospital East
Kashiwa, Chiba, Japan, 277-8577
Ehime University Hospital
Toon, Ehime, Japan, 791-0295
Iwate Medical University Hospital
Morioka, Iwate, Japan, 020-8505
Tohoku University Hospital
Sendai, Miyagi, Japan, 980-8574
Sasebo City General Hospital
Sasebo, Nagasaki, Japan, 857-8511
Heart Life Hospital
Nakagami, Okinawa, Japan, 901-2492
Shimane University Hospital
Izumo, Shimane, Japan, 693-8501
Kyushu University Hospital
Fukuoka, Japan, 812-8582
National Hospital Organization Kyushu Cancer Center
Fukuoka, Japan, 811-1395
Imamura Bunin Hospital
Kagoshima, Japan, 890-0064
Kagoshima University Medical and Dental Hospital
Kagoshima, Japan, 890-8520
National Hospital Organization Kagoshima Medical Center
Kagoshima, Japan, 892-0853
Kumamoto University Hospital
Kumamoto, Japan, 860-8556
The Japanese Red Cross Nagasaki Genbaku Hospital
Nagasaki, Japan, 852-8511
Nagasaki University Hospital
Nagasaki, Japan, 852-8501
Oita Prefectual Hospital
Oita, Japan, 870-8511
National Cancer Center Hospital
Tokyo, Japan, 104-0045
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Toru Sasaki Celgene K.K.
  More Information

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01724177     History of Changes
Other Study ID Numbers: CC-5013-ATLL-002 
Study First Received: November 7, 2012
Results First Received: September 4, 2015
Last Updated: November 26, 2015
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Celgene:
Lenalidomide
ATL
ATLL

Additional relevant MeSH terms:
Lymphoma
Leukemia
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Lymphoid
Lenalidomide
Thalidomide
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 28, 2016