A Phase II, Multi-Center, Investigator-Initiated Study of Dasatinib against AITL and Other T Follicular Helper Cell Lymphoma

JRCT ID: jRCT2031190079

Registered date:20/08/2019

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Relapsed/refractory T Follicular Helper Cell Lymphoma
• Date of first enrollment: 20/11/2019
• Target sample size: 18
• Study type: Interventional

Intervention(s)

Dasatinib will be orally administered at a dose of 100 mg/day for 30 consecutive days, and for 90 consecutive days in total as long as the subject does not meet the criteria for discontinuation of the drugs for this study. After the end of oral administration, the study (study period) will be completed after a 30-day post-observation period.
A subject who has no safety problem when he/she completed receiving the drug until day 90 and show complete response (CR), partial response (PR) or stable disease (SD), and for whom the principal investigator judges it necessary to continue administration, is allowed to receive the drug continuously until 30 days before the end of study (until 30 days before the last visit, the last day of post observation of this study) as long as the subject does not meet the criteria for discontinuation.

Outcome(s)

• Primary Outcome: Overall response rate (ORR): best overall response according to central review

Secondary Outcome

(1) Overall response rate (ORR): best overall response according to study doctors
(2) ORR in a subject population associated with RHOA mutation
(3) ORR of the whole and by disease type
(4) Complete response rate (CRR)
(5) Complete response rate (CRR) based on PET-CT (PET-CRR)
(6) Partial response rate based on PET-CT (PET-PRR)
(7) Progression-free survival (PFS)
(8) Overall survival (OS)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both
• Include criteria: (1)Diagnosed as having angioimmunoblastic T-cell lymphoma (AITL), follicular T-cell lymphoma (FTCL), nodal T-cell lymphomas with T-follicular helper cell phenotype (nPTCL-TFH) or peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) by histopathological evaluation by biopsy at each investigational sites. (2)Correspond to one or more of the following. AITL in the preceding paragraph is not limited to this. A. Immunohistochemical test of biopsy samples (two or more of PD1, ICOS, CXCL13, BCL6, CXCR5 are positive for tumor cells.) B. Immunohistochemical test or flow cytometry of a biopsy sample confirmed positive for tumor cells CD10. C. The DNA of the biopsy sample has been confirmed to be positive for the G17V mutation of the RHOA gene. Relapse after at least 1 regimen of chemotherapy to target diseases before enrollment, or SD or PD with the latest regimen. (3)One or more lesions other than skin that can be measured in two directions orthogonal to each other in a CT tomographic image. The size of the lesion should be 1.5 cm or more for nodular lesions and 1.0 cm or more for extranodal lesions. (4)Relapse after at least 1 regimen of chemotherapy to target diseases before enrollment, or SD or PD with the latest regimen (5)Able to provide with tumor tissue samples (FFPE) at the initial or relapsed time (6)Males and females aged 20 years or older (at the time of obtaining consent) (7)Performance status (PS) of 0 to 2 according to the ECOG criteria (8)Organ functions maintained that meet the following criteria. A. WBC >= 2,000 /microliter B. Neutrophils >= 1,000 /microliter C. Platelets >= 75,000 /microliter D. Hemoglobin >= 8.0 g/dL E. SpO2 >= 95% (9)Having given the patient s written consent to participation in the study

Exclude criteria

(1)Patients with clinical findings of central nervous system (CNS) invasion attributable to lymphoma. Neurological evaluation and head CT/MRI and lumbar puncture should be performed for patients with suspected CNS invasion in order to exclude CNS lesions. (2)Patients with poor-controlled systemic fungal, bacterial, or viral infection (unresolved and persistent infection-related signs/symptoms despite appropriate antibiotics, antiviral therapies, and/or other therapies) (3)Patients infected with human immunodeficiency virus (HIV), Human T-lymphotropic virus type-1 (HTLV-1) or hepatitis C virus (HCV), or those who have findings of active hepatitis B virus (HBV) infection shown below (HBsAg-positive, HBsAg-negative, with anti-HBs antibody-positive and/or anti-HBc antibody-positive and viral DNA detectable) (4)Renal function disorder (creatinine clearance calculated by the Cockcroft-Gault formula, <30 mL/min) or hepatic function disorder [total serum bilirubin level, >2.0 mg/dL (34 micromol/L) (except the case of Gilbert symptoms or identified invasion of lymphoma into the liver or pancreas), serum transaminase (AST or ALT), >3 times of the upper limit of normal level (except the case associated with lymphoma)] (5)Patients with a medical history of malignant tumor other than diseases targeted in this study and/or a histry of radiation therapy. However, patients who underwent surgery for radical cure and have shown no signs of relapse for 5 years can be included. Patients with the following medical history/complications can be included. (basal or squamous cell carcinoma of the skin, intraepithelial carcinoma of uterine cervix, intraepithelial carcinoma of breast, Accidental histological findings of prostate cancer using tumor, nodes, and metastasis (TNM) clinical staging system (T1a or T1b), Early gastric cancer for which endoscopic mucosal resection or endoscopic submucosal dissection was performed)
(6)Patients who are using any other study drugs, whatever types they may be, at the start of administration of the drugs for this study, or have used other study drugs within 4 weeks. Patients who continuously have medically-critical adverse events because of the pretreatment, regardless of its duration. (7)Patients who received or will receive prior treatment corresponding to the following 1) to 3) by the start of administration of the drug for this study. 1) Blood transfusion, albumin preparation, G-CSF: within 1 week 2) Patients who are receiving any systemic steroids for antitumor effects (except continuous administration of low-dose steroids, for example, a dose of 10 mg/day in terms of prednisolone, to the primary disease since before obtaining consent) or chemotherapy (within 4 weeks) 3) Antibody therapy for anti-tumor effect: within 12 weeks (8)Patients who have or are suspected to have hypersensitivity to active ingredients or other ingredients of the study drug (9)Women who are pregnant, planning to be pregnant, or breastfeeding Women of childbearing potential are excluded if they do not agree to follow instructions on contraception during a period from the start of the study until the end of study drug administration plus 31 days, consisting of an ovulation cycle of 30 days and additional 25 hours (1 day) which is a period 5 times as long as the elimination half-life of the study drug (3 to 5 hours). Furthermore, men that have a female partner of childbearing potential are excluded if they do not agree to follow instructions on contraception for 91 days, consisting of a spermatogenic cycle (90 days) in addition to a period 5 times as long as the elimination half-life of the study drug (3 to 5 hours). Women of childbearing potential are all women who have experienced the first menstruation, have no history of reproductive sterilization (hysterectomy or bilateral oophorectomy), and have not reached menopause. Menopause is defined as amenorrhea not by any factors for at least 12 months in women aged > 45 years. (10)Serious active cardiac diseases as follows within past 6 months (congestive heart failure, class IV according to New York Heart Association (NYHA), unstable angina pectoris or angina pectoris requiring surgical or medical treatment, myocardial infarction, arrhythmia requiring treatment) (11)Patients who are restricted from freedom because of legal judgment or managerial decision (12)Patients who have a past history of pretreatment with dasatinib and/or other tyrosine kinase inhibitors (13)Patients who are judged to lack ability to consent (14)In addition to the above, patients who were judged by the principal investigator or a subinvestigator to be inappropriate to conduct the study safely

Related Information

• Primary Sponsor: Chiba Shigeru
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development