A Phase 2 Multicenter Study Evaluating the Safety and the Efficacy of KTE-X19 in Adult Japanese Subjects with Relapsed/Refractory Mantle Cell Lymphoma or Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (JKART-1)
Study of KTE-X19 in Adult Japanese Subjects with Relapsed/Refractory Mantle Cell Lymphoma or Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (JKART-1)
Ikuta Mari
Gilead Sciences, K.K.
1-9-2, Marunouchi, Chiyoda-ku, Tokyo
+81-3-6837-0834
ClinicalTrialGSJ@gilead.com
Clinical Operations
Gilead Sciences, K.K.
1-9-2, Marunouchi, Chiyoda-ku, Tokyo
+81-3-5539-1935
JPClinicalOperations@gilead.com
Not Recruiting
Jan. 29, 2024
Mar. 18, 2024
21
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
<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
<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
<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
<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
