KW-0761 or Investigator's Choice in Subjects With Previously Treated Adult T-cell Leukemia-Lymphoma (ATL)
Primary Purpose
Adult T-cell Leukemia-Lymphoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
KW-0761
Pralatrexate
gemcitabine plus oxaliplatin
DHAP
Sponsored by
About this trial
This is an interventional treatment trial for Adult T-cell Leukemia-Lymphoma focused on measuring Adult T cell Leukemia-Lymphoma (ATL)
Eligibility Criteria
Inclusion Criteria:
- Males and female subjects ≥ 18 years of age
- Confirmed diagnosis of ATL (excluding smoldering subtype)
Subjects must currently have evidence of disease in at least one of the following:
- Lymph nodes
- Extranodal masses
- Spleen or liver
- Skin
- Peripheral blood
- Bone marrow
- Relapsed or refractory after at least one prior systemic therapy regimen for ATL;
- Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2 at study entry
- Resolution of all clinically significant toxic effects of prior cancer therapy to grade ≤1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI-CTCAE, v.4.0)
- Adequate hematological, hepatic and renal function
Exclusion Criteria:
- Smoldering subtype of ATL;
- Lymphomatous or acute subtype subject with > 2 prior systemic therapy regimens and who has not achieved a response (CR or PR) or maintained stable disease for at least 12 weeks on last immediate prior therapy;
- History of allogeneic transplant;
- Autologous hematopoietic stem cell transplant within 90 days of study entry;
- Untreated human immunodeficiency virus (HIV)
- Has known hepatitis C. Patients who are hepatitis C antibody positive but are hepatitis C quantitative PCR negative may be enrolled;
- Has hepatitis B based on PCR testing for hepatitis B virus DNA. Patients who are hepatitis B core antibody positive but PCR negative may be enrolled if placed on appropriate anti-hepatitis B virus prophylaxis prior to commencing treatment with KW-0761. Patients who are hepatitis B core antibody positive based on prior vaccination need not receive prophylaxis;
- Have had a malignancy in the past two years except non-melanoma skin cancers, melanoma in situ, localized cancer of the prostate with current PSA < 0.1 µg/mL, treated thyroid cancer or cervical carcinoma in situ or ductal/lobular carcinoma in situ of the breast who is currently without evidence of disease;
- Clinical evidence of central nervous system (CNS) involvement or metastasis. In subjects suspected of having CNS disease, an MRI of the brain and/or lumbar puncture should be done to confirm;
- Psychiatric illness, disability or social situation that would compromise the subject's safety or ability to provide consent, or limit compliance with study requirements;
- Significant uncontrolled intercurrent illness
- Experienced allergic reactions to monoclonal antibodies or other therapeutic proteins;
- Known active autoimmune diseases will be excluded (For example; Grave's disease; systemic lupus erythematosus; rheumatoid arthritis; Crohn's disease);
- Is pregnant (confirmed by beta human chorionic gonadotrophin [β-HCG]) or lactating.
- Prior treatment with KW-0761;
- Initiation of treatment with systemic corticosteroids while on study is only permitted for acute and brief complications of underlying disease (e.g., hypercalcemia) or for treatment related side effects (e.g., including pre-medication for infusion reaction, nausea and vomiting). Subjects on systemic corticosteroids prior to enrollment must be off for 7 days before initiation of study treatment, unless specifically indicated for the treatment of hypercalcemia. (subjects may receive inhalation corticosteroids and replacement doses of systemic corticosteroids as needed);
- Initiation of treatment with topical corticosteroids while on study is not permitted except to treat an acute rash. Subjects on a stable dose of medium or low potency topical corticosteroids for at least 4 weeks prior to Pre-treatment Visit may continue use at the same dose, although the investigator should attempt to taper the use to lowest dose tolerable;
- Have had interferon-α and/or zidovudine within 1 week, or anti-neoplastic chemotherapy, radiation, immunotherapy, or investigational medications within 2 weeks of first study treatment;
- Subjects on any immunomodulatory drug. Subjects on any immunomodulatory drug within 4 weeks of their first dose of KW-0761 are also excluded.
Sites / Locations
- Cedars-Sinai Medical Center
- University of Miami / Sylvester Comprehensive Cancer Center
- Northwestern University
- National Cancer Institute
- Washington University School of Medicine
- Hackensack University Medical Center
- Montefiore Medical Center
- Memorial Sloan Kettering
- Columbia Presbyterian
- Weill Cornell Medical College
- Cliniques Universitaires Saint-Luc
- Hospital Universitario Professor Edgard Santos- UFBA
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
- CHU de Fort de France
- Hospital Necker
- Hospital Nacional Edgardo Rebagliati Martins
- Instituto Oncologico Miraflores
- Guy's Hospital
- Imperial College
- Sandwell General Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
KW-0761
investigator's choice
Arm Description
anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab)
Comparator is investigator's choice of pralatrexate or gemcitabine plus oxaliplatin or DHAP
Outcomes
Primary Outcome Measures
Overall Response Rate
Overall Response Rate was determined based on the response in all compartments (lymph nodes, extranodal masses, spleen/liver, skin, peripheral blood, and bone marrow), referencing Tsukasaki, 2009 as follows: Complete Response (CR) = All compartments involved with disease must be CR; Uncertified Complete Response (CRu) = > 75% decrease in lymph nodes and/or extranodal disease with all other compartments involved with disease CR; Partial Response (PR) = If any compartment is CR/PR and all other compartments involved with disease are at least SD; Stable Disease (SD) = All compartments involved with disease are SD; Progressive Disease (PD) = PD in any compartment.
Lymph node and extranodal masses response ≥50% decrease by CT, skin response ≥50% decrease in mSWAT score; blood response ≥50% decrease in malignant cells by flow cytometry; normal bone marrow if abnormal at baseline. PD equals New or ≥50% increase in any compartment.
Secondary Outcome Measures
Progression Free Survival
Progression-free survival was defined as the time from the first date of treatment until the date that PD or death was first reported. Disease progression included PD in any compartment per ATL response criteria, clinical progression at the end of the randomized treatment, or disease progression reported during the follow-up period. The date of PD was the earliest date at which disease progression could be declared.
Overall Survival
The estimates and summary statistics for OS were calculated based on Kaplan-Meier method, and the median OS was 4.9 months for subjects randomized to the mogamulizumab group versus 6.87 months for subjects randomized to the Investigator's Choice group.
Change in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score
The FACT-Lym consists of a 27-item general core questionnaire (i.e., Functional Assessment of Cancer Therapy - General [FACT-G]) and a 15-item disease-specific questionnaire (Lymphoma Subscale). The FACT-G includes 4 domains: physical well-being, social/family well-being, emotional well-being, and functional well-being. The total FACT-Lym score (0-168) was obtained by summing individual subscale scores. Higher scores for the scales indicate better quality of life. Change was calculated as the value at the last observation minus the value at baseline.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01626664
Brief Title
KW-0761 or Investigator's Choice in Subjects With Previously Treated Adult T-cell Leukemia-Lymphoma (ATL)
Official Title
Multi-Center, Open-Label, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 or Investigator's Choice in Subjects With Previously Treated Adult T-cell Leukemia-Lymphoma (ATL)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
June 2012 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
February 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kyowa Kirin, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to estimate the overall response rate of subjects with relapsed or refractory Adult T-cell Leukemia-Lymphoma (ATL).
Detailed Description
CCR4 expression in ATL patients has been demonstrated to be very high and has been associated with shorter survival compared with CCR4-negative patients. KW-0761, a monoclonal antibody targeted to CCR4, has been shown to be safe and tolerable in several clinical trials in subjects with a variety of T-cell malignancies, including ATL, mycosis fungoides and Sézary syndrome. The objective of this study is to estimate the overall response rate of KW-0761 for subjects with relapsed or refractory ATL.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult T-cell Leukemia-Lymphoma
Keywords
Adult T cell Leukemia-Lymphoma (ATL)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
71 (Actual)
8. Arms, Groups, and Interventions
Arm Title
KW-0761
Arm Type
Experimental
Arm Description
anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab)
Arm Title
investigator's choice
Arm Type
Active Comparator
Arm Description
Comparator is investigator's choice of pralatrexate or gemcitabine plus oxaliplatin or DHAP
Intervention Type
Biological
Intervention Name(s)
KW-0761
Other Intervention Name(s)
mogamulizumab, POTELIGEO®
Intervention Description
1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression
Intervention Type
Drug
Intervention Name(s)
Pralatrexate
Other Intervention Name(s)
Folotyn
Intervention Description
30 mg/m2 weekly for 3 weeks followed by 1 week of no therapy until progression
Intervention Type
Drug
Intervention Name(s)
gemcitabine plus oxaliplatin
Other Intervention Name(s)
Gemzar, Eloxatin, GemOx
Intervention Description
gemcitabine 1000 mg/m2, followed by oxaliplatin 100 mg/m2 every 2 weeks until progression
Intervention Type
Drug
Intervention Name(s)
DHAP
Other Intervention Name(s)
Decadron, Dexasone, Baycadron, Platinol, Depocyt, Ara-C
Intervention Description
dexamethasone 40 mg on Day 1-4, cisplatin 100 mg/m2 on Day 1 followed by 2 doses of cytarabine 2000 mg/m2 every 4 weeks until progression
Primary Outcome Measure Information:
Title
Overall Response Rate
Description
Overall Response Rate was determined based on the response in all compartments (lymph nodes, extranodal masses, spleen/liver, skin, peripheral blood, and bone marrow), referencing Tsukasaki, 2009 as follows: Complete Response (CR) = All compartments involved with disease must be CR; Uncertified Complete Response (CRu) = > 75% decrease in lymph nodes and/or extranodal disease with all other compartments involved with disease CR; Partial Response (PR) = If any compartment is CR/PR and all other compartments involved with disease are at least SD; Stable Disease (SD) = All compartments involved with disease are SD; Progressive Disease (PD) = PD in any compartment.
Lymph node and extranodal masses response ≥50% decrease by CT, skin response ≥50% decrease in mSWAT score; blood response ≥50% decrease in malignant cells by flow cytometry; normal bone marrow if abnormal at baseline. PD equals New or ≥50% increase in any compartment.
Time Frame
every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first
Secondary Outcome Measure Information:
Title
Progression Free Survival
Description
Progression-free survival was defined as the time from the first date of treatment until the date that PD or death was first reported. Disease progression included PD in any compartment per ATL response criteria, clinical progression at the end of the randomized treatment, or disease progression reported during the follow-up period. The date of PD was the earliest date at which disease progression could be declared.
Time Frame
From date of randomization until the date of first documented progression, start of alternative therapy, or date of death from any cause, whichever came first, up to 36 months
Title
Overall Survival
Description
The estimates and summary statistics for OS were calculated based on Kaplan-Meier method, and the median OS was 4.9 months for subjects randomized to the mogamulizumab group versus 6.87 months for subjects randomized to the Investigator's Choice group.
Time Frame
up to 36 months
Title
Change in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score
Description
The FACT-Lym consists of a 27-item general core questionnaire (i.e., Functional Assessment of Cancer Therapy - General [FACT-G]) and a 15-item disease-specific questionnaire (Lymphoma Subscale). The FACT-G includes 4 domains: physical well-being, social/family well-being, emotional well-being, and functional well-being. The total FACT-Lym score (0-168) was obtained by summing individual subscale scores. Higher scores for the scales indicate better quality of life. Change was calculated as the value at the last observation minus the value at baseline.
Time Frame
From date of randomization until the date of first documented progression, up to 36 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males and female subjects ≥ 18 years of age
Confirmed diagnosis of ATL (excluding smoldering subtype)
Subjects must currently have evidence of disease in at least one of the following:
Lymph nodes
Extranodal masses
Spleen or liver
Skin
Peripheral blood
Bone marrow
Relapsed or refractory after at least one prior systemic therapy regimen for ATL;
Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2 at study entry
Resolution of all clinically significant toxic effects of prior cancer therapy to grade ≤1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI-CTCAE, v.4.0)
Adequate hematological, hepatic and renal function
Exclusion Criteria:
Smoldering subtype of ATL;
Lymphomatous or acute subtype subject with > 2 prior systemic therapy regimens and who has not achieved a response (CR or PR) or maintained stable disease for at least 12 weeks on last immediate prior therapy;
History of allogeneic transplant;
Autologous hematopoietic stem cell transplant within 90 days of study entry;
Untreated human immunodeficiency virus (HIV)
Has known hepatitis C. Patients who are hepatitis C antibody positive but are hepatitis C quantitative PCR negative may be enrolled;
Has hepatitis B based on PCR testing for hepatitis B virus DNA. Patients who are hepatitis B core antibody positive but PCR negative may be enrolled if placed on appropriate anti-hepatitis B virus prophylaxis prior to commencing treatment with KW-0761. Patients who are hepatitis B core antibody positive based on prior vaccination need not receive prophylaxis;
Have had a malignancy in the past two years except non-melanoma skin cancers, melanoma in situ, localized cancer of the prostate with current PSA < 0.1 µg/mL, treated thyroid cancer or cervical carcinoma in situ or ductal/lobular carcinoma in situ of the breast who is currently without evidence of disease;
Clinical evidence of central nervous system (CNS) involvement or metastasis. In subjects suspected of having CNS disease, an MRI of the brain and/or lumbar puncture should be done to confirm;
Psychiatric illness, disability or social situation that would compromise the subject's safety or ability to provide consent, or limit compliance with study requirements;
Significant uncontrolled intercurrent illness
Experienced allergic reactions to monoclonal antibodies or other therapeutic proteins;
Known active autoimmune diseases will be excluded (For example; Grave's disease; systemic lupus erythematosus; rheumatoid arthritis; Crohn's disease);
Is pregnant (confirmed by beta human chorionic gonadotrophin [β-HCG]) or lactating.
Prior treatment with KW-0761;
Initiation of treatment with systemic corticosteroids while on study is only permitted for acute and brief complications of underlying disease (e.g., hypercalcemia) or for treatment related side effects (e.g., including pre-medication for infusion reaction, nausea and vomiting). Subjects on systemic corticosteroids prior to enrollment must be off for 7 days before initiation of study treatment, unless specifically indicated for the treatment of hypercalcemia. (subjects may receive inhalation corticosteroids and replacement doses of systemic corticosteroids as needed);
Initiation of treatment with topical corticosteroids while on study is not permitted except to treat an acute rash. Subjects on a stable dose of medium or low potency topical corticosteroids for at least 4 weeks prior to Pre-treatment Visit may continue use at the same dose, although the investigator should attempt to taper the use to lowest dose tolerable;
Have had interferon-α and/or zidovudine within 1 week, or anti-neoplastic chemotherapy, radiation, immunotherapy, or investigational medications within 2 weeks of first study treatment;
Subjects on any immunomodulatory drug. Subjects on any immunomodulatory drug within 4 weeks of their first dose of KW-0761 are also excluded.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Kurman, MD
Organizational Affiliation
Kyowa Hakko Kirin Pharma, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
University of Miami / Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
National Cancer Institute
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Memorial Sloan Kettering
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Columbia Presbyterian
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Cliniques Universitaires Saint-Luc
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Hospital Universitario Professor Edgard Santos- UFBA
City
Salvador, Bahia
ZIP/Postal Code
40110-060
Country
Brazil
Facility Name
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
City
Sao Paulo- SP
ZIP/Postal Code
CEP 05403-000
Country
Brazil
Facility Name
CHU de Fort de France
City
Fort De France Cedex
ZIP/Postal Code
BP 632 97261
Country
France
Facility Name
Hospital Necker
City
Paris
ZIP/Postal Code
75743
Country
France
Facility Name
Hospital Nacional Edgardo Rebagliati Martins
City
Lima
ZIP/Postal Code
Lima11
Country
Peru
Facility Name
Instituto Oncologico Miraflores
City
Lima
ZIP/Postal Code
Lima18
Country
Peru
Facility Name
Guy's Hospital
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Name
Imperial College
City
London
ZIP/Postal Code
W2 1PG
Country
United Kingdom
Facility Name
Sandwell General Hospital
City
West Midlands
ZIP/Postal Code
B71 4HJ
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
KW-0761 or Investigator's Choice in Subjects With Previously Treated Adult T-cell Leukemia-Lymphoma (ATL)
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