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 |
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Health condition(s) or Problem(s) studied | Relapsed/Refractory (r/r) Mantle Cell Lymphoma or r/r B-precursor Acute Lymphoblastic Leukemia |
Date of first enrollment | 29/01/2024 |
Target sample size | 21 |
Countries of recruitment | |
Study type | Interventional |
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 |
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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 |
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Age maximum | Not applicable |
Gender | Both |
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
Primary Sponsor | Asou Hiroya |
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Secondary Sponsor | |
Source(s) of Monetary Support | |
Secondary ID(s) |
Contact
Public contact | |
Name | Clinical Operations |
Address | 1-9-2, Marunouchi, Chiyoda-ku, Tokyo Tokyo Japan 100-6616 |
Telephone | +81-3-6629-6110 |
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 |
ClinicalTrialGSJ@gilead.com | |
Affiliation | Gilead Sciences, K.K. |