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

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

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

Study Overview

• Status: Completed
• Conditions: Peripheral T-cell Lymphoma; Adult T-cell Leukemia-Lymphoma
• Intervention / Treatment: Drug: Lenalidomide

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 811-1395
    • National Kyusyu Cancer Center
  • Kagoshima, Japan, 890-0064
    • Imamura Bun-in Hospital
  • Kumamoto, Japan, 860-8556
    • Kumamoto University Hospital
  • Nagasaki, Japan, 852-8501
    • Nagasaki University Hospital
  • Nagoya, Japan, 466-8650
    • Nagoya Daini Red Cross Hospital
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lenalidomide; 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)	Drug: Lenalidomide; 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Up to 2.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Up to 2.5 years
PK-Time to Maximum Plasma Concentration (Tmax)	PK-Time to Maximum Plasma Concentration (Tmax)	Day 8 of Cycle 1
PK-Apparent Total Body Clearance (CL/F)	PK-Apparent Total Body Clearance (CL/F)	Day 8 of Cycle 1
PK-Apparent Volume of Distribution (Vz/F)	PK-Apparent Volume of Distribution (Vz/F)	Day 8 of Cycle 1
PK-Terminal half-life (T1/2)	PK-Terminal half-life (T1/2)	Day 8 of Cycle 1
PK-Area under the Plasma concentration time curve (AUC)	PK-Area under the Plasma concentration time curve (AUC)	Day 8 of Cycle 1
Accumulation ratio (Cmax)	Accumulation ratio (Cmax)	Day 8 of Cycle 1
Accumulation ratio (AUCτ)	Accumulation ratio (AUCτ)	Day 8 of Cycle 1
PK-Maximum Concentration in Plasma (Cmax)	PK-Maximum Concentration in Plasma (Cmax)	Day 8 of cycle 1

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Hiroya Asou, MD, Celgene KK

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2010
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 20, 2013

Study Registration Dates

• First Submitted: July 22, 2010
• First Submitted That Met QC Criteria: July 23, 2010
• First Posted (Estimate): July 26, 2010

Study Record Updates

• Last Update Posted (Actual): November 8, 2019
• Last Update Submitted That Met QC Criteria: November 6, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: PTCL; Peripheral T-cell Lymphoma; HTLV-1; Adult T-cell Leukemia-Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Leukemia, Lymphoid; Lymphoma; Leukemia; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Leukemia, T-Cell; Leukemia-Lymphoma, Adult T-Cell; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide
• Other Study ID Numbers: CC-5013-ATLL-001