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

JRCT ID: jRCT2063230095

Registered date:30/01/2024

Basic Information

• Recruitment status: Recruiting
• 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
• 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

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
- 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 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
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

<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
- 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
- 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>
- 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
- 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

<ALL Cohort>
- 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
- Presence of CNS-3 disease defined as detectable cerebrospinal blast cells in a sample of CSF with >= 5 WBCs per mm3 with or without neurological changes, and
- Presence of CNS-2 disease defined as detectable cerebrospinal blast cells in a sample of CSF with <5 WBCs per mm3 with neurological changes
- History or presence of any CNS disorder such as a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, or cerebral edema within the last 2 years
- 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