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

Relapsed/Refractory Mantle Cell Lymphoma Clinical Trial

— JKART-1  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06253663
• Other study ID #: KT-US-472-0149
• Status: Recruiting
• Phase: Phase 2
• Start date: March 18, 2024
• Est. completion date: May 2027

Study information

• Verified date: June 2024
• Source: Gilead Sciences
• Contact: Medical Information
• Phone: 844-454-5483(1-844-454-KITE)
• Email: medinfo[@]kitepharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Recruiting
• Enrollment: 21
• Est. completion date: May 2027
• Est. primary completion date: May 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, Mantle-Cell
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia
• Relapsed/Refractory Mantle Cell Lymphoma

Intervention

Drug:
• KTE-X19
A single infusion of chimeric antigen receptor (CAR) T cells
• Cyclophosphamide
Administered intravenously
• Fludarabine
Administered intravenously

Locations

Country	Name	City	State
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	Juntendo University Hospital	Tokyo
Japan	National Cancer Center Hospital	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Kite, A Gilead Company

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MCL Cohort: Objective Response Rate (ORR) Per Investigator Assessment	ORR is defined as the incidence of a complete remission (CR) or a partial remission (PR) per the Lugano Classification.	Up to 24 months
Primary	ALL Cohort: Overall Complete Remission (OCR) Rate	OCR rate is defined as the percentage of participants achieving CR/complete remission with incomplete hematologic recovery (CRi) per investigator assessment.	Up to 24 months
Secondary	MCL Cohort: Duration of Response (DOR)	DOR is defined as time from first objective response to disease progression per indication specific response criteria or death from any cause.	Up to 24 months
Secondary	MCL Cohort: Best Objective Response (BOR)	BOR is defined as the incidence of CR, PR, Stable disease (SD) or progressive disease (PD) or unevaluable as best response to treatment.	Up to 24 months
Secondary	MCL Cohort: Progression-Free Survival (PFS)	PFS is defined as time from enrollment or KTE-X19 infusion to disease progression per indication specific response criteria or death from any cause.	Up to 24 months
Secondary	MCL Cohort: Levels of Cytokines in Serum		Up to Day 28
Secondary	ALL Cohort: Minimal Residual Disease (MRD) Negativity Rate	The incidence of a minimal residual disease response (MRD-). MRD- is defined as MRD < 10^-6 per the standard assessment.	Up to 24 months
Secondary	ALL Cohort: Allogeneic Stem Cell Transplant (alloSCT) rate	The percentage of participants receiving alloSCT as the 1st next therapy after KTE-X19 infusion.	Up to 24 months
Secondary	ALL Cohort: Relapse-Free Survival (RFS)	RFS is defined as the time from enrollment or KTE-X19 infusion date to the date of disease relapse or death from any cause.	Up to 24 months
Secondary	ALL Cohorts: DOR	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.	Up to 24 months
Secondary	MCL and ALL Cohort: Levels of Anti-Cluster of Differentiation 19 (Anti-CD19) CAR T Cells in Blood		Up to 24 months
Secondary	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
Secondary	MCL and ALL Cohorts: Overall Survival (OS)	OS is defined as the time from enrollment or KTE-X19 infusion to death from any cause.	Up to 24 months
Secondary	MCL and ALL Cohorts: Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values		First infusion date up to 24 months

External Links

•   Gilead Clinical Trials Website