Relapsed and/or Refractory B-cell Lymphoma
Conditions
Brief summary
The goal of this clinical study is to learn more about the safety and effectiveness 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.
Interventions
DRUGCyclophosphamide
Lymphodepleting chemotherapy administered intravenously
DRUGFludarabine
Lymphodepleting chemotherapy administered intravenously
BIOLOGICALKITE-363
A single infusion of CAR-transduced autologous T cells administered intravenously
BIOLOGICALKITE-753
A single infusion of CAR-transduced autologous T cells administered intravenously
Sponsors
Kite, A Gilead Company
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: for Phase 1a/b and Phase 2 * 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
for Phase 1a/b and Phase 2 \- History of chimeric antigen receptor (CAR) therapy or other genetically modified T cell therapy. * 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 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. History of a hepatitis B or C infection is permitted if the viral load is undetectable per quantitative polymerase chain reaction (qPCR) or nucleic acid testing. * Individuals with suspicion and/or evidence of primary or secondary CNS lymphoma. * 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 90 days. * Individuals with full thickness lymphoma involvement of the gastric or intestinal lining and/or transmural gastrointestinal (GI) tract involvement, or with concern for gastric or intestinal perforation or known contained gastric or intestinal perforation. * 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a: Percentage of Participants Experiencing Adverse Events Defined as Dose-limiting Toxicities (DLTs) After the Infusion of KITE-363 or KITE-753 | Up to 28 days | 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 and KITE-753 as per investigator's assessment. | 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. |
| Phase 2: ORR as per central assessment for KITE-753 | Up to 15 years | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a/b: Percentage of Participants Experiencing Adverse Events (AEs) After the Infusion of KITE-363 and KITE-753 | Up to 15 years | — |
| Phase 1a/b: Percentage of Participants Experiencing Serious AEs (SAEs) After the Infusion of KITE-363 and KITE-753 | Up to 15 years | — |
| Phase 1a/b: Time To Next Treatment (TTNT) for KITE-363 and KITE-753 | Up to 15 years | 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. |
| Phase 1a/b: Complete Response (CR) Rate for KITE-363 and KITE-753 | 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. |
| Phase 1a/b: Duration of Response (DOR) for KITE-363 and KITE-753 | 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. |
| Phase 1a/b: Progression-Free Survival (PFS) for KITE-363 and KITE-753 | Up to 15 years | 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. |
| Phase 1a/b: Overall Survival (OS) for KITE-363 and KITE-753 | Up to 15 years | OS is defined as the time from KITE-363 or KITE-753 infusion to death from any cause. |
| Phase 1a/b: Percentage of Participants who Develop Antibodies to KITE-363 and KITE-753 Chimeric Antigen Receptor (CAR) T Cells | Enrollment; up to 12 months | — |
| Phase 1a/b: Levels of KITE-363 and KITE-753 CAR T Cells | Up to 15 years | — |
| Phase 1a/b: Peak Serum Levels of Key Analytes Homeostatic/Proliferative Cytokines: Interleukin (IL)-2, IL-7, and IL-15 | Up to 3 months | — |
| Phase 1a/b: 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 |
| Phase 1a/b: Peak Serum Levels of Key Analytes Correlates of Acute Phase Response: C-Reactive Protein (CRP) | Up to 3 months | — |
| Phase 1a/b: Peak Serum Levels of Key Analytes Correlates of Acute Phase Response: Ferritin | Up to 3 months | — |
| Phase 1a/b: Peak Serum Levels of Key Analytes Correlates of Acute Phase Response: Soluble IL-2 Receptor Alpha (Sil-2Rα) | Up to 3 months | — |
| Phase 1a/b: 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 | — |
| Phase 1a/b: Peak Serum Levels of Key Analytes Immune-Effector Molecules: Perforin, Granzyme A, and Granzyme B | Up to 3 months | — |
| Phase 2: CR rate for KITE-753 | Up to 15 years | — |
| Phase 2: DOR for KITE-753 | Up to 15 years | — |
| Phase 2: PFS for KITE-753 | Up to 15 years | — |
| Phase 2: OS for KITE-753 | Up to 15 years | — |
| Phase 2: Percentage of Participants Experiencing Adverse Events (AEs) After the Infusion of KITE-753 | Up to 15 years | — |
| Phase 2: Percentage of Participants Experiencing Serious AEs (SAEs) After the Infusion of KITE-753 | Up to 15 years | — |
Countries
Australia, Canada, Germany, Netherlands, United Kingdom, United States
Contacts
CONTACTMedical Information
STUDY_DIRECTORKite Study Director
Kite, A Gilead Company
Outcome results
None listed