Back to resultsStudy of KITE-363 or KITE-753 in Participants With Relapsed and/or Refractory B-cell Lymphoma
Primary Purpose
Relapsed and/or Refractory B-cell Lymphoma
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Cyclophosphamide
Fludarabine
KITE-363
KITE-753
Sponsored by
About this trial
This is an interventional treatment trial for Relapsed and/or Refractory B-cell Lymphoma
Eligibility Criteria
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 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 (hepatitis B surface antigen 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.
Sites / Locations
- Banner MD Anderson Cancer CenterRecruiting
- Stanford Cancer InstituteRecruiting
- University of MD, Greenebaum Comprehensive Cancer CenterRecruiting
- Columbia University Irving Medical CenterRecruiting
- University of Rochester Medical CenterRecruiting
- The University of Texas, MD Anderson Cancer CenterRecruiting
- Academisch Medisch Centrum
- King's College HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
KITE-363
KITE-753
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Percentage of Participants Experiencing Adverse Events (AEs) After the Infusion of KITE-363 or KITE-753
Percentage of Participants Experiencing Serious AEs (SAEs) After the Infusion of KITE-363 or KITE-753
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.
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.
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.
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.
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.
Percentage of Participants who Develop Antibodies to KITE-363 or KITE-753 Chimeric Antigen Receptor (CAR) T Cells
Levels of KITE-363 or KITE-753 CAR T Cells and Analytes (Including Cytokines) in the Blood
Peak Serum Levels of Key Analytes Homeostatic/Proliferative Cytokines: Interleukin (IL)-2, IL-7, and IL-15
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
Peak Serum Levels of Key Analytes Correlates of Acute Phase Response: C-Reactive Protein (CRP)
Peak Serum Levels of Key Analytes Correlates of Acute Phase Response: Ferritin
Peak Serum Levels of Key Analytes Correlates of Acute Phase Response: Soluble IL-2 Receptor Alpha (Sil-2Rα)
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)
Peak Serum Levels of Key Analytes Immune-Effector Molecules: Perforin, Granzyme A, and Granzyme B
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04989803
Brief Title
Study of KITE-363 or KITE-753 in Participants With Relapsed and/or Refractory B-cell Lymphoma
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 27, 2021 (Actual)
Primary Completion Date
April 2024 (Anticipated)
Study Completion Date
January 2041 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kite, A Gilead Company
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed and/or Refractory B-cell Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
114 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
KITE-363
Arm Type
Experimental
Arm Description
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.
Arm Title
KITE-753
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Lymphodepleting chemotherapy administered intravenously
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Lymphodepleting chemotherapy administered intravenously
Intervention Type
Biological
Intervention Name(s)
KITE-363
Intervention Description
A single infusion of CAR-transduced autologous T cells administered intravenously
Intervention Type
Biological
Intervention Name(s)
KITE-753
Intervention Description
A single infusion of CAR-transduced autologous T cells administered intravenously
Primary Outcome Measure Information:
Title
Phase 1a: Percentage of Participants Experiencing Adverse Events Defined as Dose-limiting Toxicities (DLTs) After the Infusion of KITE-363 or KITE-753
Description
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.
Time Frame
Up to 28 days
Title
Phase 1b: Objective Response Rate (ORR) for KITE-363 or KITE-753
Description
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.
Time Frame
Up to 15 years
Secondary Outcome Measure Information:
Title
Percentage of Participants Experiencing Adverse Events (AEs) After the Infusion of KITE-363 or KITE-753
Time Frame
Up to 15 years
Title
Percentage of Participants Experiencing Serious AEs (SAEs) After the Infusion of KITE-363 or KITE-753
Time Frame
Up to 15 years
Title
Time To Next Treatment (TTNT) for KITE-363 or KITE-753
Description
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.
Time Frame
Up to 15 years
Title
Complete Response (CR) Rate for KITE-363 or KITE-753
Description
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.
Time Frame
Up to 15 years
Title
Duration of Response (DOR) for KITE-363 or KITE-753
Description
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.
Time Frame
Up to 15 years
Title
Progression-Free Survival (PFS) for KITE-363 or KITE-753
Description
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.
Time Frame
Up to 15 years
Title
Overall Survival (OS) for KITE-363 or KITE-753
Description
OS is defined as the time from KITE-363 or KITE-753 infusion to death from any cause.
Time Frame
Up to 15 years
Title
Percentage of Participants who Develop Antibodies to KITE-363 or KITE-753 Chimeric Antigen Receptor (CAR) T Cells
Time Frame
Enrollment; up to 12 months
Title
Levels of KITE-363 or KITE-753 CAR T Cells and Analytes (Including Cytokines) in the Blood
Time Frame
Up to 15 years
Title
Peak Serum Levels of Key Analytes Homeostatic/Proliferative Cytokines: Interleukin (IL)-2, IL-7, and IL-15
Time Frame
Up to 3 months
Title
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)
Description
IFN-γ=Interferon-Gamma, IL-1 Receptor Antagonist=IL-1RA
Time Frame
Up to 3 months
Title
Peak Serum Levels of Key Analytes Correlates of Acute Phase Response: C-Reactive Protein (CRP)
Time Frame
Up to 3 months
Title
Peak Serum Levels of Key Analytes Correlates of Acute Phase Response: Ferritin
Time Frame
Up to 3 months
Title
Peak Serum Levels of Key Analytes Correlates of Acute Phase Response: Soluble IL-2 Receptor Alpha (Sil-2Rα)
Time Frame
Up to 3 months
Title
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)
Time Frame
Up to 3 months
Title
Peak Serum Levels of Key Analytes Immune-Effector Molecules: Perforin, Granzyme A, and Granzyme B
Time Frame
Up to 3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Medical Information
Phone
844-454-5483(1-844-454-KITE)
Email
medinfo@kitepharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kite Study Director
Organizational Affiliation
Kite, A Gilead Company
Official's Role
Study Director
Facility Information:
Facility Name
Banner MD Anderson Cancer Center
City
Gilbert
State/Province
Arizona
ZIP/Postal Code
85234
Country
United States
Individual Site Status
Recruiting
Facility Name
Stanford Cancer Institute
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Recruiting
Facility Name
University of MD, Greenebaum Comprehensive Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Recruiting
Facility Name
Columbia University Irving Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Individual Site Status
Recruiting
Facility Name
The University of Texas, MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
Academisch Medisch Centrum
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Name
King's College Hospital
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://www.gileadclinicaltrials.com/study/?id=KT-US-499-0150
Description
Gilead Clinical Trials Website
Learn more about this trial
Study of KITE-363 or KITE-753 in Participants With Relapsed and/or Refractory B-cell Lymphoma
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