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JAPANESE
国立保健医療科学院
JRCT ID: jRCT2063230095

Registered date:30/01/2024

Study of KTE-X19 in Adult Japanese Subjects with Relapsed/Refractory Mantle Cell Lymphoma or Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia

Basic Information

Recruitment status Recruiting
Health condition(s) or Problem(s) studiedRelapsed/Refractory (r/r) Mantle Cell Lymphoma or r/r B-precursor Acute Lymphoblastic Leukemia
Date of first enrollment29/01/2024
Target sample size21
Countries of recruitment
Study typeInterventional
Intervention(s)Subjects will receive 1 infusion of KTE-X19.

Outcome(s)

Primary Outcome<MCL Cohort> Objective response rate (ORR) (CR + PR) per the Lugano Classification {Cheson 2014} per investigator assessment <ALL Cohort> Overall complete remission (OCR) rate (CR + complete remission with incomplete hematological recovery [CRi]) per investigator assessment
Secondary Outcome<MCL Cohort> - Duration of response (DOR) - Best Objective response (BOR) - Progression free survival (PFS) - Overall survival (OS) - Incidence of AEs and clinically significant changes in safety laboratory values - Levels of anti-CD19 CAR T cells in blood - Levels of cytokines in serum <ALL Cohort> - DOR - Minimal residual disease (MRD) negativity rate - alloSCT rate (Can proceed to alloSCT upon confirmation of response to CAR-T cell therapy) - OS - Relapse-free survival (RFS) - Incidence of AEs and clinically significant changes in safety laboratory values - Level of anti-CD19 CAR T cells in blood

Key inclusion & exclusion criteria

Age minimum>= 18age old
Age maximumNot applicable
GenderBoth
Include criteria<MCL Cohort> - Pathologically confirmed MCL with documentation or either overexpression of cyclin D1 or presence of t(11;14) - Up to 5 prior regimens for MCL. Prior therapy must have included: - Anthracycline-, bendamustine-, or high-dose cytarabine- containing chemotherapy, and - Anti-CD20 monoclonal antibody therapy, and - Bruton's tyrosine kinase inhibitor (BTKi) - Relapsed or refractory disease, defined by the following: - Disease progression after last regimen, or - Refractory disease is defined failure to achieve partial response (PR) or complete response (CR) to the last regimen - At lease 1 measurable lesion - Toxicities due to prior therapy must be stable and recovered to <= Grade 1 - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Adequate bone marrow function as indicated by: - Absolute neutrophil count (ANC) >= 1,000/microL - Platelet count >= 75,000/microL. For subjects with bone marrow involvement, platelet count >= 50,000/microL is acceptable. - Absolute lymphocyte count >= 100/microL - Adequate renal, hepatic, pulmonary, and cardiac function defined as: - Creatinine clearance (CrCl) or eCrCl by Cockcroft Gault >= 60 cc/min - Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) <= 2.5 upper limit of normal (ULN) - Total bilirubin <=1.5 mg/dl, except in subjects with Gilbert's syndrome - Cardiac ejection fraction >= 50%, no evidence of significant pericardial effusion, and no clinically significant electrocardiogram (ECG) findings. - No clinically significant pleural effusion - Baseline oxygen saturation > 92% on room air <ALL Cohort> - Relapsed or refractory B-ALL defined as one of the following: - Relapsed or refractory disease after one line of systemic therapy: - Primary refractory, or - First relapse if first remission <=12 months - Relapsed or refractory disease after two or more lines of systemic therapy - Relapsed or refractory disease after allogenic transplant provided subject is at least 100 days from SCT at the time of enrollment and off of immunosuppressive medications for at least 4 weeks prior to enrollment - Morphological disease in the bone marrow (> 5% blasts) - Subjects with Ph+ disease are eligible if they are intoleratnt to tyrosine kinase inhibitor (TKI) therapy, or if they have relapsed/ refractory disease despite treatment with at least 2 different TKIs - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Adequate bone marrow function as indicated by: - Absolute neutrophil count (ANC) >= 500/microL - Platelet count >= 50,000/microL unless in the opinion of the investigator cytopenia is due to underlying leukemia and is potentially reversible with leukemia therapy. - Absolute lymphocyte count >= 100/microL - Adequate renal, hepatic, pulmonary, and cardiac function defined as: - CrCl or eCrCl by Cockcroft Gault >= 60 cc/min - Serum ALT, AST <= 2.5 x ULN - Total bilirubin <= 1.5 mg/dl, except in subjects with Gilbert's syndrome - Left ventricular ejection fraction >= 50%, no evidence of significant pericardial effusion, no NYHA class III/IV functional classification, and no clinically significant arrhythmias. - No clinically significant pleural effusion - Baseline oxygen saturation > 92% on room air - In subjects previously treated with blinatumab, CD19 tumor expression on blasts obtained from bone marrow or peripheral blood is documented after completion of the most recent prior line of therapy
Exclude criteria<MCL Cohort> - History of malignancy other than non-melanomatous skin cancer or carcinoma in situ unless disease-free for at least 3 years - Autologous stem cell transplant (autoSCT) within 6 weeks of planned KTE-X19 infusion - History of allogenic stem cell transplant (alloSCT) with the exception of subjects with no donor cells detected on chimerism > 100 days after alloSCT - Prior CD19 targeted therapy - Prior CAR therapy or other genetically modified T-cell therapy - Infection with immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) - Subjects with detectable cerebraospinal fluid (CSF) malignant cells or brain metastases or with a history of Central Nervous System (CNS) lymphoma, CSF malignant cells, or brain metastases - Subjects with atrial or cardiac ventricular lymphoma involvement <ALL Cohort> - History of malignancy other than non-melanoma skin cancer or carcinoma in situ (unless disease free for at least 3 years) - CNS abnormalities - Presence of CNS-2 or CNS-3 disease (those with CNS-1 or CNS-2 without clinically evident neurological changes are eligible to participate in the study) - History or presence of any CNS disorder such as a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, any autoimmune disease with CNS involvement, posterior reversible encephalopathy syndrome, or cerebral edema within the last 2 years - Infection with HIV, HBV, or HCV - Those with the below prior medications: - Salvage systemic therapy (including chemotherapy, TKIs for Ph+ ALL, and blinatumomab) within 1 week or 5 half-lives (whichever is shorter) prior to enrollment - Prior CD19 directed therapy other than blinatumomab - History of Grade 4 neurologic event or Grade 4 CRS {Lee 2019} with prior CD19-directed therapy - Any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy within 3 half-lives prior to enrollment - Acute graft versus host disease (GVHD) Grade II-IV by Glucksberg criteria or severity B-D by IBMTR index; acute or chronic GVHD requiring systemic treatment within 4 weeks prior to enrollment

Related Information

Contact

Public contact
Name Clinical Operations
Address 1-9-2, Marunouchi, Chiyoda-ku, Tokyo Tokyo Japan 100-6616
Telephone +81-3-6629-6110
E-mail JPClinicalOperations@gilead.com
Affiliation Gilead Sciences, K.K.
Scientific contact
Name Hiroya Asou
Address 1-9-2, Marunouchi, Chiyoda-ku, Tokyo Tokyo Japan 100-6616
Telephone +81-3-6629-6110
E-mail ClinicalTrialGSJ@gilead.com
Affiliation Gilead Sciences, K.K.