Study of KITE-363 or KITE-753 in Participants With Relapsed and/or Refractory B-cell Lymphoma

A Phase 1 Open-label, Multicenter Study Evaluating the Safety and Efficacy of KITE-363 or KITE-753, Autologous Anti-CD19/CD20 CAR T-cell Therapies, in Subjects With Relapsed and/or Refractory B-cell Lymphoma

The goal of this clinical study is to learn more about the safety and dosing of the study drugs, KITE-363 and KITE-753, in participants with relapsed and/or refractory B-cell lymphoma.

Study Overview

• Status: Recruiting
• Conditions: Relapsed and/or Refractory B-cell Lymphoma
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: KITE-363; Biological: KITE-753

Detailed Description

Eligible study participants who have received IP administration with either KITE-363 or KITE-753 will transition to a separate Long-term Follow-up study (Study KT-US-982-5968) to complete the remainder of the 15-year follow-up assessments.

• Study Type: Interventional
• Enrollment (Estimated): 114
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Medical Information; Phone Number: 844-454-5483(1-844-454-KITE); Email: medinfo@kitepharma.com

Study Locations

• Germany
  • Wuerzburg, Germany, 97080
    • Recruiting
    • Universitätsklinikum Würzburg
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Recruiting
    • Academisch Medisch Centrum
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • Recruiting
    • King's College Hospital
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Recruiting
      • Banner MD Anderson Cancer Center
  • California
    • Stanford, California, United States, 94305
      • Recruiting
      • Stanford Cancer Institute
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of MD, Greenebaum Comprehensive Cancer Center
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center
    • Rochester, New York, United States, 14642
      • Recruiting
      • University of Rochester Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas, MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Relapsed and/or refractory B-cell lymphoma (R/R BCL).
• At least 1 measurable lesion.
• Adequate organ and bone marrow (BM) function.

Key Exclusion Criteria:

• History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg, cervix, bladder, or breast) unless disease free and without anticancer therapy (with the exception of hormonal therapy in the case of breast cancer) for at least 3 years.
• History of Richter's transformation of chronic leukemic lymphoma, small lymphocytic lymphoma, or lymphoplasmacytic lymphoma.
• History of allogeneic stem cell transplant (allo-SCT).
• Auto-SCT within 6 weeks before the planned KITE-363 or KITE-753 infusion.
• Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requires intravenous (IV) antimicrobials for management.
• Known history of human immunodeficiency virus (HIV) infection, hepatitis B virus (HBV) hepatitis B surface (HBs) antigen (HBsAg) positive infection, or hepatitis C (anti-hepatitis C virus [HCV] positive) infection.
• Individuals with detectable cerebrospinal fluid (CSF) malignant cells or brain metastases or a history of central nervous system (CNS) lymphoma, primary CNS lymphoma, or spinal epidural involvement.
• History or presence of a CNS disorder.
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, active arrhythmia, New York Heart Association Class II or greater congestive heart failure or other clinically significant cardiac disease within the 6 months before enrollment.
• Primary immunodeficiency.
• History of autoimmune disease resulting in or requiring systemic immunosuppression and/or systemic disease-modifying agents within the last 2 years.
• History of non-line associated, clinically significant deep-vein thrombosis or pulmonary embolism requiring therapeutic anticoagulation within the 6 months before enrollment.
• Females of childbearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Females who have undergone surgical sterilization or have been postmenopausal for at least 2 years are not considered to be of childbearing potential.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KITE-363; Phase 1a (Dose Escalation): Participants with r/r large B-cell lymphoma will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single target starting dose of KITE-363 chimeric antigen receptor (CAR) transduced autologous T cells. Based on dose limiting toxicities (DLTs) observed in the first cohort, additional participants will be enrolled and administered escalating dose of KITE-363. Phase 1b (Dose Expansion): After completion of dose escalation, additional participants with r/r B-cell lymphoma across different disease indications will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single dose of KITE-363 at 1 or more dose-level deemed to be tolerable.	Drug: Cyclophosphamide; Lymphodepleting chemotherapy administered intravenously; Drug: Fludarabine; Lymphodepleting chemotherapy administered intravenously; Biological: KITE-363; A single infusion of CAR-transduced autologous T cells administered intravenously
Experimental: KITE-753; Phase 1a (Dose Escalation): Participants with r/r large B-cell lymphoma will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single target starting dose of KITE-753 chimeric antigen receptor (CAR) transduced autologous T cells. Based on dose limiting toxicities (DLTs) observed in the first cohort, additional participants will be enrolled and administered escalating dose of KITE-753. Phase 1b (Dose Expansion): After completion of dose escalation, additional participants with r/r B-cell lymphoma across different disease indications will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single dose of KITE-753 at 1 or more dose-level deemed to be tolerable.	Drug: Cyclophosphamide; Lymphodepleting chemotherapy administered intravenously; Drug: Fludarabine; Lymphodepleting chemotherapy administered intravenously; Biological: KITE-753; A single infusion of CAR-transduced autologous T cells administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1a: Percentage of Participants Experiencing Adverse Events Defined as Dose-limiting Toxicities (DLTs) After the Infusion of KITE-363 or KITE-753	DLTs are defined as the KITE-363-related or KITE-753-related events with onset within the first 28 days after the infusion of KITE-363 or KITE-753 respectively.	Up to 28 days
Phase 1b: Objective Response Rate (ORR) for KITE-363 or KITE-753	ORR is defined as the percentage of participants with a complete response (CR) or a partial response (PR) by the International Working Group (IWG) Lugano Response Criteria for Malignant Lymphoma (Cheson 2014) as determined by investigator assessment.	Up to 15 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Serum Levels of Key Analytes Homeostatic/Proliferative Cytokines: Interleukin (IL)-2, IL-7, and IL-15		Up to 3 months
Peak Serum Levels of Key Analytes Inflammatory/Immune Modulating Cytokines: IFN-γ, IL-6, IL-10, IL-17, IL-1RA, Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF), and Tumor Necrosis Factor-Alpha (TNF-α)	IFN-γ=Interferon-Gamma, IL-1 Receptor Antagonist=IL-1RA	Up to 3 months
Peak Serum Levels of Key Analytes Correlates of Acute Phase Response: C-Reactive Protein (CRP)		Up to 3 months
Peak Serum Levels of Key Analytes Correlates of Acute Phase Response: Ferritin		Up to 3 months
Peak Serum Levels of Key Analytes Correlates of Acute Phase Response: Soluble IL-2 Receptor Alpha (Sil-2Rα)		Up to 3 months
Peak Serum Levels of Key Analytes Chemokines: IL-8, C-X-C Motif Chemokine Ligand-10 (CXCL-10), and Monocyte Chemotactic Protein-1 (MCP-1)		Up to 3 months
Peak Serum Levels of Key Analytes Immune-Effector Molecules: Perforin, Granzyme A, and Granzyme B		Up to 3 months
Percentage of Participants Experiencing Adverse Events (AEs) After the Infusion of KITE-363 or KITE-753		Up to 15 years
Percentage of Participants Experiencing Serious AEs (SAEs) After the Infusion of KITE-363 or KITE-753		Up to 15 years
Time To Next Treatment (TTNT) for KITE-363 or KITE-753	TTNT is defined as the time from KITE-363 or KITE-753 infusion to the next anticancer treatment (including stem cell transplantation [SCT]) or death from any cause, whichever occurs first.	Up to 15 years
Complete Response (CR) Rate for KITE-363 or KITE-753	CR rate is defined as the incidence of a CR by the IWG Lugano Response Criteria for Malignant Lymphoma (Cheson 2014) as determined by investigator assessment.	Up to 15 years
Duration of Response (DOR) for KITE-363 or KITE-753	DOR is defined only for participants who experience an objective response and is the time from the first objective response to disease progression per the IWG Lugano Classification or death due to any cause, whichever occurs first.	Up to 15 years
Progression-Free Survival (PFS) for KITE-363 or KITE-753	PFS is defined as the time of KITE-363 or KITE-753 infusion to disease progression per IWG Lugano Response Criteria for Malignant Lymphoma (Cheson 2014) or death from any cause, whichever occurs first.	Up to 15 years
Overall Survival (OS) for KITE-363 or KITE-753	OS is defined as the time from KITE-363 or KITE-753 infusion to death from any cause.	Up to 15 years
Percentage of Participants who Develop Antibodies to KITE-363 or KITE-753 Chimeric Antigen Receptor (CAR) T Cells		Enrollment; up to 12 months
Levels of KITE-363 or KITE-753 CAR T Cells and Analytes (Including Cytokines) in the Blood		Up to 15 years

Collaborators and Investigators

• Sponsor: Kite, A Gilead Company
• Investigators: Study Director: Kite Study Director, Kite, A Gilead Company

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2021
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: July 26, 2021
• First Submitted That Met QC Criteria: July 26, 2021
• First Posted (Actual): August 4, 2021

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: KT-US-499-0150; 2020-000562-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes