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: 13 December 2021
• Main ID: EUCTR2011-005738-20-FR
• Date of registration: 05/09/2012
• 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: 19/03/2013
• 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, Germany, 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 approved informed consent form in accordance with regulatory and institutional guidelines. Written informed consent must be obtained prior to performing any study-related procedure;
2) Males and female subjects = 18 years of age at the time of enrollment;
3) Confirmed diagnosis of ATL:
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
9) Adequate hepatic function:
a. bilirubin = 2 times the specific institutional ULN;
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 ( 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;
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, symptothermal, post-ovulation methods and withdrawal are not acceptable methods of contraception) during the study and for 3 months after the last dose.
WOCBP includes any female who has experienced menarche and who has not undergone successful surgical sterilization or is not postmenopausal (defined as amenorrhea = 12 consecutive months);
13) Male subjects and their female partners of child bearing potential must be willing to use an appropriate method of 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, symptothermal, post-ovulation methods and withdrawal are not acceptable methods of contraception) during the study and for 3 months after the last dose.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this
Exclusion criteria:
1) History of allogeneic transplant;
2) Autologous hematopoietic stem cell transplant within 90 days of study entry;
3) 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;
4) Has known or tests positive for hepatitis C;
5) Has known or tests positive for hepatitis B. Patients who are negative on qualitative HBV DNA assay may be enrolled;
6) 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;
7) Clinical evidence of 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;
8) Psychiatric illness, disability or social situation that would compromise the subject’s safety or ability to provide consent, or limit compliance with study requirements;
9) Significant uncontrolled intercurrent illness including, but not limited to:
a. uncontrolled infection requiring antibiotics;
b. clinically significant cardiac disease (class III or IV of the New York Heart Association [NYHA] classification);
c. unstable angina pectoris;
d. angioplasty, stenting, or myocardial infarction within 6 months;
e. uncontrolled hypertension (systolic blood pressure (BP) >160 mm Hg or diastolic BP >100 mmHg, found on two consecutive measurements separated by a 1-week period) despite two anti-hypertensive medications;
f. clinically significant cardiac arrhythmia; or
g. uncontrolled diabetes.
10) 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.
11) Experienced allergic reactions to monoclonal antibodies or other therapeutic proteins;
12) Known active autoimmune disease will be excluded. (For example; Grave’s disease; systemic lupus erythematosus; rheumatoid arthritis; Crohn’s disease).
13) Is pregnant (confirmed by beta human chorionic gonadotrophin [ß-HCG]) or lactating.
14) Prior treatment with KW-0761;
15) Initiation of treatment with systemic steroids 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 steroids 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 steroid should be tapered to discontinuation as rapidly as possible. All tests to document extent of disease must be performed after completion of steroid treatment and prior to first study treatment (subjects may receive inhalation steroids and replacement doses of systemic steroids as needed);
16) Initiation of treatment with topical steroids while on study is not permitted except to treat an acute rash. Assessment of skin disease must be documented after completion of steroid treatment and before study treatment is reinitiated;
17) Have had inter

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

Health Condition(s) or Problem(s) studied

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

Treatment of patients with relapsed or refractory ATL
MedDRA version: 15.0 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)

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

Pharmaceutical Form:
INN or Proposed INN: OXALIPLATIN
CAS Number: 61825-94-3

Pharmaceutical Form:
INN or Proposed INN: DEXAMETHASONE
CAS Number: 50-02-2

Pharmaceutical Form:
INN or Proposed INN: CYTARABINE
CAS Number: 147-94-4

Pharmaceutical Form:
INN or Proposed INN: CISPLATIN
CAS Number: 15663-27-1

Primary Outcome(s)

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.

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

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)

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.

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 ID(s)

2011-005738-20-BE

0761-009

Source(s) of Monetary Support

Kyowa Hakko Kirin Pharma, Inc.

Ethics review

Status: Approved
Approval date: 19/03/2013
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