Clinical trial NCT06253663: Study of KTE-X19 in Adult Japanese Participants With Relapsed/Refractory Mantle Cell Lymphoma or Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Relapsed/Refractory Mantle Cell Lymphoma
Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2024-02-12
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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)
Primary purpose: TREATMENT

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.

Eligibility 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/Exclusion criteria may apply.

Primary outcomes:
measure: MCL Cohort: Objective Response Rate (ORR) Per Investigator Assessment
timeFrame: Up to 24 months
measure: ALL Cohort: Overall Complete Remission (OCR) Rate
timeFrame: Up to 24 months
Secondary outcomes:
measure: MCL Cohort: Duration of Response (DOR)
timeFrame: Up to 24 months
measure: MCL Cohort: Best Objective Response (BOR)
timeFrame: Up to 24 months
measure: MCL Cohort: Progression-Free Survival (PFS)
timeFrame: Up to 24 months
measure: MCL Cohort: Levels of Cytokines in Serum
timeFrame: Up to Day 28
measure: ALL Cohort: Minimal Residual Disease (MRD) Negativity Rate
timeFrame: Up to 24 months
measure: ALL Cohort: Allogeneic Stem Cell Transplant (alloSCT) rate
timeFrame: Up to 24 months
measure: ALL Cohort: Relapse-Free Survival (RFS)
timeFrame: Up to 24 months
measure: ALL Cohorts: DOR
timeFrame: Up to 24 months
measure: MCL and ALL Cohort: Levels of Anti-Cluster of Differentiation 19 (Anti-CD19) CAR T Cells in Blood
timeFrame: Up to 24 months
measure: MCL and ALL Cohorts: Percentages of Participants Experiencing Treatment-emergent Adverse Event (TEAEs), Serious Adverse Event (SAEs) and Deaths
timeFrame: First infusion date up to 24 months
measure: MCL and ALL Cohorts: Overall Survival (OS)
timeFrame: Up to 24 months
measure: MCL and ALL Cohorts: Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values
timeFrame: First infusion date up to 24 months
Other outcomes:
Locations:
city: Chiba
country: Japan
facility: Chiba University Hospital
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Hokkaido
country: Japan
facility: Hokkaido University Hospital
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Miyagi
country: Japan
facility: Tohoku University Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: Juntendo University Hospital
city: Tokyo
country: Japan
facility: Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital
Study officials:
affiliation: Kite, A Gilead Company
name: Kite Study Director
role: STUDY_DIRECTOR
References: