Study of KTE-X19 in Adult Japanese Participants With Relapsed/Refractory Mantle Cell Lymphoma or Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia
- Conditions
- Relapsed/Refractory B-precursor Acute Lymphoblastic LeukemiaRelapsed/Refractory Mantle Cell Lymphoma
- Interventions
- Registration Number
- NCT06253663
- Lead Sponsor
- Kite, A Gilead Company
- Brief Summary
The goal of this clinical study is to learn more about KTE-X19, and how safe and effective it is in adult Japanese participants with relapsed/refractory (r/r) Mantle Cell Lymphoma (MCL) or r/r B-precursor Acute Lymphoblastic Leukemia (B-ALL).
The primary objectives of this study are to evaluate the efficacy of KTE-X19, as measured by:
* Objective response rate (ORR) per investigator assessment, in adult Japanese participants with r/r MCL
* Overall complete remission (OCR) defined as complete remission (CR) and complete remission with incomplete hematologic recovery (CRi) per investigator assessment, in adult Japanese participants with r/r ALL
- Detailed Description
After completing at least 24 months in the study, all participants who received an infusion of KTE-X19 will be transitioned to a separate long-term follow-up (LTFU) study (KT-US-982-5968) to complete the remainder of the 15-year follow-up assessments.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 21
MCL Cohort:
-
Pathologically confirmed MCL, with documentation of 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 remission (CR) to the last regimen
-
At least 1 measurable lesion. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy
- If the only measurable disease is lymph node disease, at least 1 lymph node should be ≥ 2 cm
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 allogeneic transplant provided individuals 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)
-
Individuals with Philadelphia-positive (Ph+) disease are eligible if they are intolerant to tyrosine kinase inhibitor (TKI) therapy, or if they have relapsed/refractory disease despite treatment with at least 2 different TKIs
Key
MCL Cohort:
- History of malignancy other than nonmelanomatous skin cancer or carcinoma in situ (eg, cervix, bladder, breast) unless disease-free for at least 3 years
- Autologous SCT (autoSCT) within 6 weeks of planned KTE-X19 infusion
- History of alloSCT with the exception of individuals 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
- History of hypersensitivity to any of the ingredients of KTE-X19 or to any of the animal-derived ingredients (bovine and rodent) used in the manufacturing process of KTE-X19
ALL Cohort:
- Diagnosis of Burkitt's leukemia/lymphoma according to World Health Organization (WHO) classification or chronic myelogenous leukemia lymphoid blast crisis
- History of malignancy other than non-melanoma skin cancer or carcinoma in situ (eg, cervix, bladder, breast) unless disease free for at least 3 years
- History of hypersensitivity to any of the ingredients of KTE-X19 or to any of the animal-derived ingredients (bovine and rodent) used in the manufacturing process of KTE-X19
Note: Other protocols defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ALL Cohort- KTE-X19 KTE-X19 Participants will receive cyclophosphamide 900 mg/m\^2/day intravenously (IV) for 1 day and fludarabine 25 mg/m\^2/day IV lymphodepletion chemotherapy for 3 days followed by KTE-X19 administered intravenously at a target dose of 1 x 10\^6 19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of 1 x 10\^8 anti-CD19 CAR T cells will be administered. MCL Cohort- KTE-X19 KTE-X19 Participants will receive cyclophosphamide 500 mg/m\^2/day intravenously (IV) and fludarabine 30 mg/m\^2/day IV lymphodepletion chemotherapy for 3 days followed by KTE-X19 administered intravenously at a target dose of 2 x 10\^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of 2 x 10\^8 anti-CD19 CAR T cells will be administered. MCL Cohort- KTE-X19 Fludarabine Participants will receive cyclophosphamide 500 mg/m\^2/day intravenously (IV) and fludarabine 30 mg/m\^2/day IV lymphodepletion chemotherapy for 3 days followed by KTE-X19 administered intravenously at a target dose of 2 x 10\^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of 2 x 10\^8 anti-CD19 CAR T cells will be administered. ALL Cohort- KTE-X19 Cyclophosphamide Participants will receive cyclophosphamide 900 mg/m\^2/day intravenously (IV) for 1 day and fludarabine 25 mg/m\^2/day IV lymphodepletion chemotherapy for 3 days followed by KTE-X19 administered intravenously at a target dose of 1 x 10\^6 19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of 1 x 10\^8 anti-CD19 CAR T cells will be administered. MCL Cohort- KTE-X19 Cyclophosphamide Participants will receive cyclophosphamide 500 mg/m\^2/day intravenously (IV) and fludarabine 30 mg/m\^2/day IV lymphodepletion chemotherapy for 3 days followed by KTE-X19 administered intravenously at a target dose of 2 x 10\^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of 2 x 10\^8 anti-CD19 CAR T cells will be administered. ALL Cohort- KTE-X19 Fludarabine Participants will receive cyclophosphamide 900 mg/m\^2/day intravenously (IV) for 1 day and fludarabine 25 mg/m\^2/day IV lymphodepletion chemotherapy for 3 days followed by KTE-X19 administered intravenously at a target dose of 1 x 10\^6 19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of 1 x 10\^8 anti-CD19 CAR T cells will be administered.
- Primary Outcome Measures
Name Time Method MCL Cohort: Objective Response Rate (ORR) Per Investigator Assessment Up to 24 months ORR is defined as the incidence of a complete remission (CR) or a partial remission (PR) per the Lugano Classification.
ALL Cohort: Overall Complete Remission (OCR) Rate Up to 24 months OCR rate is defined as the percentage of participants achieving CR/complete remission with incomplete hematologic recovery (CRi) per investigator assessment.
- Secondary Outcome Measures
Name Time Method ALL Cohort: Allogeneic Stem Cell Transplant (alloSCT) rate Up to 24 months The percentage of participants receiving alloSCT as the 1st next therapy after KTE-X19 infusion.
MCL and ALL Cohort: Levels of Anti-Cluster of Differentiation 19 (Anti-CD19) CAR T Cells in Blood Up to 24 months MCL Cohort: Duration of Response (DOR) Up to 24 months DOR is defined as time from first objective response to disease progression per indication specific response criteria or death from any cause.
MCL Cohort: Best Objective Response (BOR) Up to 24 months BOR is defined as the incidence of CR, PR, Stable disease (SD) or progressive disease (PD) or unevaluable as best response to treatment.
MCL Cohort: Progression-Free Survival (PFS) Up to 24 months PFS is defined as time from enrollment or KTE-X19 infusion to disease progression per indication specific response criteria or death from any cause.
MCL Cohort: Levels of Cytokines in Serum Up to Day 28 ALL Cohort: Minimal Residual Disease (MRD) Negativity Rate Up to 24 months The incidence of a minimal residual disease response (MRD-). MRD- is defined as MRD \< 10\^-6 per the standard assessment.
ALL Cohort: Relapse-Free Survival (RFS) Up to 24 months RFS is defined as the time from enrollment or KTE-X19 infusion date to the date of disease relapse or death from any cause.
MCL and ALL Cohorts: Overall Survival (OS) Up to 24 months OS is defined as the time from enrollment or KTE-X19 infusion to death from any cause.
ALL Cohorts: DOR Up to 24 months DOR is defined as the time between their first complete remission (CR or CRi) to relapse or any death in the absence of documented relapse.
MCL and ALL Cohorts: Percentages of Participants Experiencing Treatment-emergent Adverse Event (TEAEs), Serious Adverse Event (SAEs) and Deaths First infusion date up to 24 months MCL and ALL Cohorts: Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values First infusion date up to 24 months
Trial Locations
- Locations (9)
Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital
🇯🇵Tokyo, Japan
Chiba University Hospital
🇯🇵Chiba, Japan
Kyushu University Hospital
🇯🇵Fukuoka, Japan
Hokkaido University Hospital
🇯🇵Hokkaido, Japan
Kyoto University Hospital
🇯🇵Kyoto, Japan
Tohoku University Hospital
🇯🇵Miyagi, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
National Cancer Center Hospital
🇯🇵Tokyo, Japan
Juntendo University Hospital
🇯🇵Tokyo, Japan