Multicenter, Randomized, Open-label, Parallel-group Study to Compare mLSG15 + KW-0761 to mLSG15

Multicenter, Randomized, Open-label, Parallel-group Study to Compare mLSG15 + KW-0761 to mLSG15 in Subjects With CCR4-positive Adult T-cell Leukemia-lymphoma (Untreated Primary Disease)

This is a multicenter, randomized, open-label, parallel-group study to compare mLSG15 + KW-0761 to mLSG15 in subjects with CCR4-positive adult T-cell leukemia-lymphoma (untreated primary disease). The primary variable is an efficacy of KW-0761 used as an add-on therapy to mLSG15 as measured in terms of complete response rate (CR/CRu) in the best overall response assessment for antitumor effect. The secondary variables include response rate (CR/CRu/PR) in the best overall response assessment for antitumor effect, complete or response rates by lesion site in the best overall response assessment for antitumor effect, progression-free survival and overall survival. The safety and pharmacokinetic profiles of KW-0761 will be also determined.

Study Overview

• Status: Completed
• Conditions: Adult T-cell Leukemia-Lymphoma
• Intervention / Treatment: Drug: VCAP/AMP/VECP(mLSG15); Biological: KW-0761

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan
    • Fukuoka University Hospital
  • Fukuoka, Japan
    • Kyushu University Hospital
  • Fukuoka, Japan
    • National Kyushu Cancer Center
  • Kagoshima, Japan
    • Kagoshima University Hospital
  • Kagoshima, Japan
    • Imamura Bun-in Hospital
  • Kitakyushu, Japan
    • Kokura Memorial Hospital
  • Kumamoto, Japan
    • Kumamoto University Hospital
  • Kumamoto, Japan
    • National Hospital Organization Kumamoto Medical Center
  • Kumamoto, Japan
    • NTT West Japan Kyushu Hospital
  • Nagasaki, Japan
    • Nagasaki University Hospital
  • Nagasaki, Japan
    • The Japanese Red Cross Nagasaki Genbaku Hospital
  • Nagoya, Japan
    • Aichi Cancer Center Hospital
  • Nagoya, Japan
    • Nagoya City University Hospital
  • Oita, Japan
    • Oita Prefectural Hospital
  • Okinawa, Japan
    • Heartlife Hospital
  • Omura, Japan
    • National Hospital Organization Nagasaki Medical Center
  • Sasebo, Japan
    • Sasebo City General Hospital
  • Tokyo, Japan
    • National Cancer Center Hospital
  • Toon, Japan
    • Ehime University 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:

• Subjects who have been positive for serum anti-human T-cell lymphotropic virus type I antibody
• Subjects with hematologically or pathohistologically confirmed as peripheral lymphoid tumor which surface antigen analysis has identified to be of T-cell origin
• Subjects who have been classified into acute subtype, the lymphoma subtype or chronic subtype with poor prognostic factors
• Subjects who have been positive for CCR4 by CCR4 expression analysis
• Subjects who have never been treated for adult T-cell leukemia-lymphoma
• Subjects who have presented enlarged lymph nodes, tumor nodules in extranodal organs, abnormal lymphocytes in peripheral blood or cutaneous lesions
• Subjects with a performance status of 0 to 2
• Subjects who have been negative for HBs antigen and anti-HCV antibody
• Subjects who have given written voluntary informed consent to participate in the study

Exclusion Criteria:

• Subjects who are scheduled for transplant therapy such as hematopoietic stem-cell transplantation
• Subjects who had myocardial infarction within 12 months before study enrollment or who have cardiac disease that may worsen during treatment with doxorubicin
• Subjects who have been positive for anti-HIV antibody
• Subjects with active multiple cancer
• Subjects with a history of allergic reactions to therapeutic antibodies
• Subjects who require emergency radiotherapy for treating the symptoms caused by bulky masses or who may require such radiotherapy after the start of the study
• Subjects who are pregnant, lactating or of childbearing potential, or who are planning to have children

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: mLSG15	Drug: VCAP/AMP/VECP(mLSG15); VCAP(Vincristine Sulfate, Cyclophosphamide Hydrate, Doxorubicin Hydrochloride, Prednisolone); AMP(Doxorubicin Hydrochloride, Ranimustine, Prednisolone); VECP(Vindesine Sulfate, Etoposide, Carboplatin, Prednisolone)
Experimental: mLSG15 + KW-0761	Biological: KW-0761; VCAP/AMP/VECP(mLSG15) + KW-0761

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Complete response rate in the best overall response assessment for antitumor effect	After cycle 2 and cycle 4

Secondary Outcome Measures

Outcome Measure	Time Frame
Response rate in the best overall response assessment for antitumor effect, complete or response rates by lesion site in the best overall response assessment for antitumor effect	After cycle 2 and cycle 4.
Progression-free survival and Overall survival	During the study period at least once every two months in the first year and once every three months in the second and subsequent years.
Adverse events	During the study period
anti-KW-0761 antibody	Before 1st and 5th dosing, 14 days after 8th or last dosing and at the start of post-treatment.
Plasma KW-0761 concentrations and pharmacokinetic parameters	Before and after 1st, 2nd, 3rd, 4th, 5th, 6th, 7th and 8th dosing, 14 days after 8th or last dosing, and at the start of post-treatment.

Collaborators and Investigators

• Sponsor: Kyowa Kirin Co., Ltd.

Publications and helpful links

General Publications

• Ishida T, Jo T, Takemoto S, Suzushima H, Uozumi K, Yamamoto K, Uike N, Saburi Y, Nosaka K, Utsunomiya A, Tobinai K, Fujiwara H, Ishitsuka K, Yoshida S, Taira N, Moriuchi Y, Imada K, Miyamoto T, Akinaga S, Tomonaga M, Ueda R. Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: a randomized phase II study. Br J Haematol. 2015 Jun;169(5):672-82. doi: 10.1111/bjh.13338. Epub 2015 Mar 2.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: July 30, 2010
• First Submitted That Met QC Criteria: July 30, 2010
• First Posted (Estimate): August 2, 2010

Study Record Updates

• Last Update Posted (Actual): March 30, 2017
• Last Update Submitted That Met QC Criteria: March 29, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, Lymphoid; Lymphoma; Leukemia; Leukemia, T-Cell; Leukemia-Lymphoma, Adult T-Cell; Antineoplastic Agents; Mogamulizumab
• Other Study ID Numbers: 0761-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No