Study of KTE-X19 in Adult Japanese Participants With Relapsed/Refractory Mantle Cell Lymphoma or Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (JKART-1)

Gilead Sciences

Status and phase: Enrolling; Phase 2

Conditions: Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia; Relapsed/Refractory Mantle Cell Lymphoma

Treatments: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: KTE-X19

Study type: Interventional

Funder types: Industry

Identifiers

NCT06253663

KT-US-472-0149

Details and patient eligibility

About

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

Full 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.

Enrollment: 21 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

21 participants in 2 patient groups

MCL Cohort- KTE-X19

Experimental group

Description:

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.

Treatment:

Drug: Fludarabine

Drug: KTE-X19

Drug: Cyclophosphamide

ALL Cohort- KTE-X19

Experimental group

Description:

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.

Treatment:

Drug: Fludarabine

Drug: KTE-X19

Drug: Cyclophosphamide