Treatment of patients with relapsed or refractory ATL MedDRA version: 17.1 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)
Conditions
Sponsors
Kyowa Hakko Kirin Pharma, Inc.
Eligibility
Sex/Gender
All
Inclusion 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, 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 the 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 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, symptothermal, post-ovulation methods and withdrawal are not acceptable methods of contraception) during the study and for 6 months after the last dose of study drug. 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 without an alternative medical cause). * In Belgium, abstinence is not accept
Exclusion criteria
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. 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 comparators according to local SmPCs/Prescribing Information would preclude treatment with that option; 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 document extent of disease must be performed after completion of corticosteroid treatment and prior to first study treatment (subjects may receive intra-articular corticosteroid injections, intraocular corticosteroid drops, inhalation or nasal corticosteroids and replacement doses of systemic corticosteroids as needed); 19) Subjects on a stable dose of medi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Primary end point(s): 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
| Measure | Time frame |
|---|---|
| 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. | — |
Countries
Belgium, Brazil, France, Martinique, Peru, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Kyowa Hakko Kirin Pharma, Inc.
Outcome results
None listed