A clinical trial to test if KW-0761 (an antibody) or a choice of chemotherapy will work in patients with recurrent or unsuccessfully treated Adult T-Cell Lymphoma (ATL).

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2011-005738-20-GB
• Date of registration: 20/06/2012
• Prospective Registration: Yes
• Primary sponsor: Kyowa Hakko Kirin Pharma, Inc.
• Public title: A clinical trial to test if KW-0761 (an antibody) or a choice of chemotherapy will work in patients with recurrent or unsuccessfully treated Adult T-Cell Lymphoma (ATL).
• Scientific 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)
• Date of first enrolment: 18/09/2012
• Target sample size: 70
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-005738-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: yes; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Brazil, France, Martinique, Peru, United Kingdom, United States

Contacts

• Name: Clinical Trial Information
• Affiliation: Kyowa Hakko Kirin Pharma, Inc.

• Name: Clinical Trial Information
• Affiliation: Kyowa Hakko Kirin Pharma, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1) Voluntarily signed and dated IRB/EC informed consent form. Written informed consent must be obtained prior to performing any study-related procedure;
2) Males and female subjects = 18 years of age ;
3) Confirmed diagnosis of ATL, excluding smoldering
subtype:
a. Subjects must have been determined to be positive for HTLV-1 virus
b. Subjects must have hematologically or pathohistologically diagnosed peripheral lymphoid tissue which surface antigen analysis has identified to be of T-cell origin
4) Subjects must currently have evidence of disease in at least one of the following:
a. Lymph nodes
b. Extranodal masses
c. Spleen or liver
d. Skin
e. Peripheral blood
f. Bone marrow
5) Relapsed or refractory after at least one prior systemic therapy regimen for ATL;
6) Eastern Cooperative Oncology Group (ECOG) performance status score of = 2 at study entry;
7) The subject has 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) excluding the specifications required in 8, 9 and 10 below;
8) Adequate hematological function:
a. absolute neutrophil count (ANC) = 1,000/mm3;
b. platelets = 50,000 / mm3;
c. If ANC and/or platelet count is less than the level specified above in the setting of documented bone marrow involvement, investigator may discuss individual case with the Medical Monitor, who will determine if subject may be enrolled
Note: Retesting for values out of criteria will be permitted. Subjects being recruited to this study will not necessarily meet the inclusion/exclusion criteria for baseline organ function, for investigator's choice regimens due to the leukemic nature of their illness and bone marrow involvement by the neoplastic process; this should be taken into account by the
investigator and if necessary discussed with the medical monitor.
9) Adequate hepatic function:
a. bilirubin = 2 times the specific institutional ULN; except for subjects with Gilbert’s Syndrome;
b. aspartate transaminase (AST) and alanine transaminase (ALT) each = 2.5 x ULN or = 5.0 x ULN in the presence of known hepatic ATL involvement.
Note: Retesting for values out of criteria will be permitted
10) Adequate renal function:
a. serum creatinine < 2 x ULN
or
b. calculated creatinine clearance > 60 mL/min using the Cockroft-Gault formula (or >30 mL/min with documented renal infiltration);
Note: Retesting for values out of criteria will be permitted
11) Women of childbearing potential (WOCBP) must have a negative pregnancy test within 7 days of receiving study medication and prior to each treatment cycle;
12) WOCBP must agree to use effective contraception, defined as oral contraceptives, double barrier method (condom plus spermicide or diaphragm plus spermicide) or practice true abstinence from sexual intercourse* (periodic abstinence ,e.g., calendar, ovulation, s
Exclusion criteria:
1) Smoldering subtype of ATL;
2) 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;
3) History of allogeneic transplant;
4) Autologous hematopoietic stem cell transplant within 90 days of study entry;
5) Untreated human immunodeficiency virus (HIV). Patients on HIV therapy with undetectable viral loads as measured by HIV RNA quantitative real time PCR may be enrolled;
6) Has known hepatitis C. Patients who are hepatitis C antibody positive but are hepatitis C quantitative PCR negative may be enrolled;
7) 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;
8) Have had a malignancy in the past two years. However, subjects with non-melanoma skin cancers, melanoma in situ, localized cancer of the prostate with current PSA of < 0.1 µg/mL, treated thyroid cancer or cervical carcinoma in situ or ductal/lobular carcinoma in situ of the breast with in the past two years may enroll as long as there is no current evidence of disease;
9) Clinical evidence of CNS involvement or metastasis.
10) Psychiatric illness, disability or social situation that would compromise the subject’s safety or ability to provide consent, or limit compliance with study requirements;
11) Significant uncontrolled intercurrent illness (as per protocol).
12) Subjects with a history of moderate or severe psoriasis or with psoriasis associated with systemic symptoms e.g., arthropathy, or with a 1st degree relative with history of psoriasis that required systemic medical intervention.
13) Experienced allergic reactions to monoclonal antibodies or other therapeutic proteins;
14) Subjects randomized to the investigator’s choice treatment group may not receive a treatment they
have had previously or any contra-indication to any of the investigator's choice
regimens according to local SmPCs/Prescribing
Information ;
15) Known active autoimmune disease will be excluded. (For example; Grave’s disease; systemic lupus erythematosus; rheumatoid arthritis; Crohn’s disease).
16) Is pregnant or lactating.
17) Prior treatment with KW-0761;
18) 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. However, once the calcium returns to normal and the subject is on protocol treatment, the corticosteroid should be tapered to discontinuation as rapidly as possible. All tests to docu

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Treatment of patients with relapsed or refractory ATL
MedDRA version: 17.0 Level: PT Classification code 10001416 Term: Adult T-cell lymphoma/leukaemia recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Body processes [G] - Immune system processes [G12]

Intervention(s)

Product Name: KW-0761 (Mogamulizumab)
Product Code: KW-0761
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: mogamulizumab
CAS Number: 1159266-37-1
Current Sponsor code: KW-0761
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 4-

Pharmaceutical Form:
INN or Proposed INN: GEMCITABINE
CAS Number: 95058-81-4
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 1000-

Pharmaceutical Form:
INN or Proposed INN: OXALIPLATIN
CAS Number: 61825-94-3
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 100-

Pharmaceutical Form:
INN or Proposed INN: DEXAMETHASONE
CAS Number: 50-02-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Pharmaceutical Form:
INN or Proposed INN: CYTARABINE
CAS Number: 147-94-4
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 2000-

Pharmaceutical Form:
INN or Proposed INN: CISPLATIN
CAS Number: 15663-27-1
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Main Objective: To estimate overall response rate of KW-0761 for subjects with relapsed or refractory ATL.

Primary end point(s): To estimate overall response rate of KW-0761 for subjects with relapsed or refractory ATL.

Secondary Objective: 1. To estimate the median progression free survival and overall survival rates of the KW-0761 and investigator’s choice arms of the study;
2. To compare the overall response rates between the KW-0761 and investigator’s choice arms of the study;
3. To compare the median progression free survival and overall survival rates between the KW-0761 and investigator’s choice arms of the study;
4. To estimate the median duration of response of KW-0761 and investigator’s choice within both arms for those subjects with relapsed or refractory ATL responding to treatment;
5. To determine if subjects who relapse on investigator’s choice can achieve response upon cross over to treatment with KW-0761;
6. To evaluate quality of life for subjects receiving KW-0761 and investigator’s choice;
7. To further assess the safety of KW-0761;
8. To describe the immunogenicity of KW-0761;
9. To conduct exploratory evaluation of KW-0761 exposure-response relationships.

Timepoint(s) of evaluation of this end point: Response will be evaluated at Day 26-28 of the first treatment cycle and then every 8 weeks thereafter.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Response will be evaluated at Day 26-28 of the first treatment cycle and then every 8 weeks thereafter.

Secondary end point(s): 1. To estimate the median progression free survival and overall survival rates of the KW-0761 and investigator’s choice arms of the study;
2. To compare the overall response rates between the KW-0761 and investigator’s choice arms of the study;
3. To compare the median progression free survival and overall survival rates between the KW-0761 and investigator’s choice arms of the study;
4. To estimate the median duration of response of KW-0761 and investigator’s choice within both arms for those subjects with relapsed or refractory ATL responding to treatment ;
5. To determine if subjects who relapse on investigator’s choice can achieve response upon cross over to treatment with KW-0761;
6. To evaluate quality of life for subjects receiving KW-0761 and investigator’s choice;
7. To further assess the safety of KW-0761;
8. To describe the immunogenicity of KW-0761;
9. To conduct exploratory evaluation of KW-0761 exposure-response relationships.

Secondary ID(s)

2011-005738-20-BE

0761-009

Source(s) of Monetary Support

Kyowa Hakko Kirin Pharma, Inc.

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 25/02/2018
• Date Completed: 10/02/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-005738-20/results