Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia, Relapsed/Refractory Mantle Cell Lymphoma
Conditions
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.
Interventions
DRUGKTE-X19
A single infusion of chimeric antigen receptor (CAR) T cells
DRUGCyclophosphamide
Administered intravenously
DRUGFludarabine
Administered intravenously
Sponsors
Kite, A Gilead Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participant will be enrolled into the appropriate cohort depending on the type of disease in the two cohorts: r/r Mantle Cell Lymphoma (MCL) or r/r B-precursor Acute Lymphoblastic Leukemia(B-ALL)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 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
Exclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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: 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. |
| 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. |
| 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 Cohort: Levels of Anti-Cluster of Differentiation 19 (Anti-CD19) CAR T Cells in Blood | Up to 24 months | — |
| 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: Overall Survival (OS) | Up to 24 months | OS is defined as the time from enrollment or KTE-X19 infusion to death from any cause. |
| MCL and ALL Cohorts: Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values | First infusion date up to 24 months | — |
Countries
Japan
Contacts
STUDY_DIRECTORKite Study Director
Kite, A Gilead Company
Outcome results
None listed