Study Evaluating the Safety and Efficacy of KITE-363 in Participants With Relapsed and/or Refractory B-cell Lymphoma
Study Details
Study Description
Brief Summary
The primary objective of Phase 1a of the study is to evaluate the safety of KITE-363 in participants with relapsed and/or refractory (r/r) B-cell lymphoma and to determine the dose level(s) for Phase 1b dose expansion.
The primary objective of Phase 1b of the study is to evaluate the efficacy of KITE-363 in participants with r/r B-cell lymphoma as measured by the objective response rate (ORR) defined as complete response (CR) plus partial response (PR) rates.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- Phase 1a: Percentage of Participants Experiencing Adverse Events Defined as Dose-Limiting Toxicities (DLTs) [Up to 28 days]
DLTs are defined as the KITE-363-related events with onset within the first 28 days after the infusion of KITE-363.
- Phase 1b: Objective Response Rate (ORR) [Up to 15 years]
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) [Up to 15 years]
- Percentage of Participants Experiencing Serious AEs (SAEs) [Up to 15 years]
- Time To Next Treatment (TTNT) [Up to 15 years]
TTNT is defined as the time from KITE-363 infusion to the next anticancer treatment (including stem cell transplantation [SCT]) or death from any cause, whichever occurs first.
- Complete Response (CR) Rate [Up to 15 years]
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) [Up to 15 years]
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) [Up to 15 years]
PFS is defined as the time of KITE-363 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) [Up to 15 years]
OS is defined as the time from KITE-363 infusion to death from any cause.
- Percentage of Participants who Develop Antibodies to KITE-363 CAR [Enrollment; up to 12 months]
- Levels of KITE-363 Chimeric Antigen Receptor (CAR) T Cells in the Blood [Up to 15 years]
- 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) [Up to 3 months]
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) [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]
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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Relapsed and/or refractory B-cell lymphoma (R/R BCL).
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At least 1 measurable lesion.
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Adequate organ and bone marrow (BM) function.
Key Exclusion Criteria:
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History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg, cervix, bladder, or breast) unless the individual has been disease free for at least 3 years.
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History of Richter's transformation of chronic leukemic lymphoma, small lymphocytic lymphoma, or lymphoplasmacytic lymphoma.
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History of allogeneic stem cell transplant (allo-SCT).
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Auto-SCT within 6 weeks before the planned KITE-363 infusion.
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Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requires intravenous (IV) antimicrobials for management.
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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.
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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.
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History or presence of a CNS disorder.
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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.
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Primary immunodeficiency.
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History of autoimmune disease resulting in or requiring systemic immunosuppression and/or systemic disease-modifying agents within the last 2 years.
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History of non-line associated, clinically significant deep-vein thrombosis or pulmonary embolism requiring therapeutic anticoagulation within the 6 months before enrollment.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Stanford Cancer Institute | Stanford | California | United States | 94305 |
| 2 | University of MD, Greenebaum Comprehensive Cancer Center | Baltimore | Maryland | United States | 21201 |
| 3 | The University of Texas, MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Kite, A Gilead Company
Investigators
- Study Director: Kite Study Director, Kite, A Gilead Company
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- KT-US-499-0150
- 2020-000562-41