search
Back to results

A Phase I, Multicenter, Open-label, Dose-escalation Study to Assess the Safety of Lenalidomide in Patients With Advanced Adult T-cell Leukemia-lymphoma and Peripheral T-cell Lymphomaperipheral T-cell Lymphoma

Primary Purpose

Adult T-cell Leukemia-Lymphoma, Peripheral T-cell Lymphoma

Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
Lenalidomide
Sponsored by
Celgene
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult T-cell Leukemia-Lymphoma focused on measuring Adult T-cell Leukemia-Lymphoma, Peripheral T-cell Lymphoma, PTCL, HTLV-1

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Subject must understand and voluntarily sign the written informed consent;
  2. Aged 20 years or older;
  3. Subject have a documented diagnosis of either:

    • Acute-, lymphoma-, or unfavorable chronic-type ATL or
    • Peripheral T-cell Lymphomaperipheral (PTCL)
  4. Subject have received ≥1 prior anti-cancer therapy, have achieved stable disease (SD) or better on their immediately prior therapy and have relapsed or progressed at the time of obtaining signed informed consent;
  5. Subject have an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2 at enrollment;

Exclusion Criteria:

  1. Natural Killer cell lymphoma (NK-cell lymphoma);
  2. T-cell leukemia;
  3. Cutaneous T-cell lymphoma (CTCL) including;

    • Mycosis fungoides
    • Sezary syndrome
    • CD30-positive lympho-proliferative disorders
    • Cutaneous gamma/delta T-cell lymphoma
  4. Subject have a history of central nervous system (CNS) involvement or present with CNS symptoms, and are diagnosed with CNS lymphoma by cerebrospinal fluid (CSF) cytology examination, head CT scan or brain MRI during the screening;
  5. Are pregnant or lactating;
  6. Subject have uncontrolled inter-current illness including:

    • Uncontrolled diabetes mellitus
    • Chronic congestive heart failure (NYHA 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
    • Other uncontrolled diseases
  7. Exhibit grade 4 neurological disorders;
  8. Subject have a history or complication of deep vein thrombosis or pulmonary embolism within 6 months before the start of study treatment;
  9. Develop active tuberculous disease, herpes simplex, systemic mycosis, or other active infections requiring systemic administration of antibiotics, antiviral agents, or antifungal drugs;
  10. Are tested positive for HBs antigen, anti-HCV antibody, or anti-HIV antibody;
  11. Subjects have a history or complication for which the investigator or subinvestigator deems them inappropriate for this study, or have serious diseases or mental illness that is likely to be aggravated by participation in this study;
  12. Subjects have a history of allogeneic stem cell transplantation;
  13. Subjects have received autologous stem cell transplantation within 12 weeks (84 days) of the start of study treatment;
  14. Have previously used lenalidomide;
  15. Have a history of desquamating (bullous) rash while taking thalidomide;
  16. Have received any investigational drugs (unapproved drugs in Japan) within 4 weeks (28 days) of the start of study medication;
  17. Have received chemotherapeutic agents or immunomodulators for the treatment of ATL or PTCL within 4 weeks (28 days) of the start of study treatment;
  18. Have received radiotherapy within 4 weeks (28 days) of the start of study treatment;
  19. Have a history or complication of another malignant tumor than ATL or PTCL (excluding malignant tumors below), unless the patients have been free of the disease for 5 years or longer;

    • Cutaneous basal cell carcinoma or squamous cell carcinoma
    • Cervical carcinoma in situ
    • An incidental histological finding of prostate carcinoma (TNM stage T1a or T1b)
  20. Have had any of the following abnormal measurements at screening performed within 1 week (7 days) prior to the enrollment;

    • Neutrophil count: < 1,200/µL (1.2 x 109/L)
    • Platelet count: < 75,000/µL (75 x 109/L)
    • Serum aspartate aminotransferase/ Serum glutamic oxaloacetic transaminase (AST/SGOT) or Alanine transaminase/Serum Glutamic Pyruvate Transaminase (ALT/SGPT): > 3 times the Upper Limit of Normal (ULN)
    • Bilirubin level: > 1.5 times of the ULN
    • Creatinine clearance: < 60 mL/min

Sites / Locations

  • National Kyusyu Cancer Center
  • Imamura Bun-in Hospital
  • Kumamoto University Hospital
  • Nagasaki University Hospital
  • Nagoya Daini Red Cross Hospital
  • National Cancer Center Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lenalidomide

Arm Description

Lenalidomide: 25mg daily on day1-21 of each 28days cycle (1st cohort), 25 mg daily of each 28 days (2nd cohort) or 35 mg daily of each 28 days (3rd cohort)

Outcomes

Primary Outcome Measures

The safety of lenalidomide evaluated based on the severity of adverse events and their causality
The safety of lenalidomide evaluated based on the severity of adverse events and their causality

Secondary Outcome Measures

Response
The response of ATL patient to lenalidomide will be evaluated according to the criteria proposed by the International Consensus Meeting. The response of PTCL will be assessed by the Japan Clinical Oncology Group (JCOG) response criteria that have been established by the Lymphoma Study Group of the JCOG based on criteria of Cheson et al.in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas
PK-Time to Maximum Plasma Concentration (Tmax)
PK-Time to Maximum Plasma Concentration (Tmax)
PK-Apparent Total Body Clearance (CL/F)
PK-Apparent Total Body Clearance (CL/F)
PK-Apparent Volume of Distribution (Vz/F)
PK-Apparent Volume of Distribution (Vz/F)
PK-Terminal half-life (T1/2)
PK-Terminal half-life (T1/2)
PK-Area under the Plasma concentration time curve (AUC)
PK-Area under the Plasma concentration time curve (AUC)
Accumulation ratio (Cmax)
Accumulation ratio (Cmax)
Accumulation ratio (AUCτ)
Accumulation ratio (AUCτ)
PK-Maximum Concentration in Plasma (Cmax)
PK-Maximum Concentration in Plasma (Cmax)

Full Information

First Posted
July 22, 2010
Last Updated
November 6, 2019
Sponsor
Celgene
search

1. Study Identification

Unique Protocol Identification Number
NCT01169298
Brief Title
A Phase I, Multicenter, Open-label, Dose-escalation Study to Assess the Safety of Lenalidomide in Patients With Advanced Adult T-cell Leukemia-lymphoma and Peripheral T-cell Lymphomaperipheral T-cell Lymphoma
Official Title
A Phase I, Multicenter, Open-label, Dose-escalation Study to Assess the Safety of Lenalidomide in Patients With Advanced Adult T-cell Leukemia-lymphoma and Peripheral T-cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
July 1, 2010 (Actual)
Primary Completion Date
December 1, 2013 (Actual)
Study Completion Date
December 20, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
To determine the maximum tolerated dose of lenalidomide in patients with adult T-cell leukemia-lymphoma (ATL) and peripheral T-cell lymphoma (PTCL) who have previously received therapy for ATL and PTCL

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult T-cell Leukemia-Lymphoma, Peripheral T-cell Lymphoma
Keywords
Adult T-cell Leukemia-Lymphoma, Peripheral T-cell Lymphoma, PTCL, HTLV-1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lenalidomide
Arm Type
Experimental
Arm Description
Lenalidomide: 25mg daily on day1-21 of each 28days cycle (1st cohort), 25 mg daily of each 28 days (2nd cohort) or 35 mg daily of each 28 days (3rd cohort)
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Intervention Description
Lenalidomide: 25mg daily on day 1-21 of each 28days cycle (1st cohort), 25 mg daily of each 28 days (2nd cohort, or 35 mg daily of each 28 days (3rd cohort)
Primary Outcome Measure Information:
Title
The safety of lenalidomide evaluated based on the severity of adverse events and their causality
Description
The safety of lenalidomide evaluated based on the severity of adverse events and their causality
Time Frame
Up to 2.5 years
Secondary Outcome Measure Information:
Title
Response
Description
The response of ATL patient to lenalidomide will be evaluated according to the criteria proposed by the International Consensus Meeting. The response of PTCL will be assessed by the Japan Clinical Oncology Group (JCOG) response criteria that have been established by the Lymphoma Study Group of the JCOG based on criteria of Cheson et al.in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas
Time Frame
Up to 2.5 years
Title
PK-Time to Maximum Plasma Concentration (Tmax)
Description
PK-Time to Maximum Plasma Concentration (Tmax)
Time Frame
Day 8 of Cycle 1
Title
PK-Apparent Total Body Clearance (CL/F)
Description
PK-Apparent Total Body Clearance (CL/F)
Time Frame
Day 8 of Cycle 1
Title
PK-Apparent Volume of Distribution (Vz/F)
Description
PK-Apparent Volume of Distribution (Vz/F)
Time Frame
Day 8 of Cycle 1
Title
PK-Terminal half-life (T1/2)
Description
PK-Terminal half-life (T1/2)
Time Frame
Day 8 of Cycle 1
Title
PK-Area under the Plasma concentration time curve (AUC)
Description
PK-Area under the Plasma concentration time curve (AUC)
Time Frame
Day 8 of Cycle 1
Title
Accumulation ratio (Cmax)
Description
Accumulation ratio (Cmax)
Time Frame
Day 8 of Cycle 1
Title
Accumulation ratio (AUCτ)
Description
Accumulation ratio (AUCτ)
Time Frame
Day 8 of Cycle 1
Title
PK-Maximum Concentration in Plasma (Cmax)
Description
PK-Maximum Concentration in Plasma (Cmax)
Time Frame
Day 8 of cycle 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subject must understand and voluntarily sign the written informed consent; Aged 20 years or older; Subject have a documented diagnosis of either: Acute-, lymphoma-, or unfavorable chronic-type ATL or Peripheral T-cell Lymphomaperipheral (PTCL) Subject have received ≥1 prior anti-cancer therapy, have achieved stable disease (SD) or better on their immediately prior therapy and have relapsed or progressed at the time of obtaining signed informed consent; Subject have an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2 at enrollment; Exclusion Criteria: Natural Killer cell lymphoma (NK-cell lymphoma); T-cell leukemia; Cutaneous T-cell lymphoma (CTCL) including; Mycosis fungoides Sezary syndrome CD30-positive lympho-proliferative disorders Cutaneous gamma/delta T-cell lymphoma Subject have a history of central nervous system (CNS) involvement or present with CNS symptoms, and are diagnosed with CNS lymphoma by cerebrospinal fluid (CSF) cytology examination, head CT scan or brain MRI during the screening; Are pregnant or lactating; Subject have uncontrolled inter-current illness including: Uncontrolled diabetes mellitus Chronic congestive heart failure (NYHA 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 Other uncontrolled diseases Exhibit grade 4 neurological disorders; Subject have a history or complication of deep vein thrombosis or pulmonary embolism within 6 months before the start of study treatment; Develop active tuberculous disease, herpes simplex, systemic mycosis, or other active infections requiring systemic administration of antibiotics, antiviral agents, or antifungal drugs; Are tested positive for HBs antigen, anti-HCV antibody, or anti-HIV antibody; Subjects have a history or complication for which the investigator or subinvestigator deems them inappropriate for this study, or have serious diseases or mental illness that is likely to be aggravated by participation in this study; Subjects have a history of allogeneic stem cell transplantation; Subjects 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 (bullous) 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 chemotherapeutic agents or immunomodulators for the treatment of ATL or PTCL 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 than ATL or PTCL (excluding malignant tumors below), unless the patients have been free of the disease for 5 years or longer; Cutaneous basal cell carcinoma or squamous cell carcinoma Cervical carcinoma in situ An incidental histological finding of prostate carcinoma (TNM stage T1a or T1b) Have had any of the following abnormal measurements at screening performed within 1 week (7 days) prior to the enrollment; Neutrophil count: < 1,200/µL (1.2 x 109/L) Platelet count: < 75,000/µL (75 x 109/L) Serum aspartate aminotransferase/ Serum glutamic oxaloacetic transaminase (AST/SGOT) or Alanine transaminase/Serum Glutamic Pyruvate Transaminase (ALT/SGPT): > 3 times the Upper Limit of Normal (ULN) Bilirubin level: > 1.5 times of the ULN Creatinine clearance: < 60 mL/min
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hiroya Asou, MD
Organizational Affiliation
Celgene KK
Official's Role
Study Director
Facility Information:
Facility Name
National Kyusyu Cancer Center
City
Fukuoka
ZIP/Postal Code
811-1395
Country
Japan
Facility Name
Imamura Bun-in Hospital
City
Kagoshima
ZIP/Postal Code
890-0064
Country
Japan
Facility Name
Kumamoto University Hospital
City
Kumamoto
ZIP/Postal Code
860-8556
Country
Japan
Facility Name
Nagasaki University Hospital
City
Nagasaki
ZIP/Postal Code
852-8501
Country
Japan
Facility Name
Nagoya Daini Red Cross Hospital
City
Nagoya
ZIP/Postal Code
466-8650
Country
Japan
Facility Name
National Cancer Center Hospital
City
Tokyo
ZIP/Postal Code
104-0045
Country
Japan

12. IPD Sharing Statement

Citations:
PubMed Identifier
26947199
Citation
Ogura M, Imaizumi Y, Uike N, Asou N, Utsunomiya A, Uchida T, Aoki T, Tsukasaki K, Taguchi J, Choi I, Maruyama D, Nosaka K, Chen N, Midorikawa S, Ohtsu T, Tobinai K. Lenalidomide in relapsed adult T-cell leukaemia-lymphoma or peripheral T-cell lymphoma (ATLL-001): a phase 1, multicentre, dose-escalation study. Lancet Haematol. 2016 Mar;3(3):e107-18. doi: 10.1016/S2352-3026(15)00284-7. Epub 2016 Feb 12.
Results Reference
background

Learn more about this trial

A Phase I, Multicenter, Open-label, Dose-escalation Study to Assess the Safety of Lenalidomide in Patients With Advanced Adult T-cell Leukemia-lymphoma and Peripheral T-cell Lymphomaperipheral T-cell Lymphoma

We'll reach out to this number within 24 hrs