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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04989803




Registration number
NCT04989803
Ethics application status
Date submitted
26/07/2021
Date registered
4/08/2021
Date last updated
27/12/2024

Titles & IDs
Public title
Study of KITE-363 or KITE-753 in Participants With Relapsed and/or Refractory B-cell Lymphoma
Scientific 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
Secondary ID [1] 0 0
2020-000562-41
Secondary ID [2] 0 0
KT-US-499-0150
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed and/or Refractory B-cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Fludarabine
Treatment: Other - KITE-363
Treatment: Other - KITE-753

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.

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.


Treatment: Drugs: Cyclophosphamide
Lymphodepleting chemotherapy administered intravenously

Treatment: Drugs: Fludarabine
Lymphodepleting chemotherapy administered intravenously

Treatment: Other: KITE-363
A single infusion of CAR-transduced autologous T cells administered intravenously

Treatment: Other: KITE-753
A single infusion of CAR-transduced autologous T cells administered intravenously
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1a: Percentage of Participants Experiencing Adverse Events Defined as Dose-limiting Toxicities (DLTs) After the Infusion of KITE-363 or KITE-753
Timepoint [1] 0 0
Up to 28 days
Primary outcome [2] 0 0
Phase 1b: Objective Response Rate (ORR) for KITE-363 or KITE-753
Timepoint [2] 0 0
Up to 15 years
Secondary outcome [1] 0 0
Percentage of Participants Experiencing Adverse Events (AEs) After the Infusion of KITE-363 or KITE-753
Timepoint [1] 0 0
Up to 15 years
Secondary outcome [2] 0 0
Percentage of Participants Experiencing Serious AEs (SAEs) After the Infusion of KITE-363 or KITE-753
Timepoint [2] 0 0
Up to 15 years
Secondary outcome [3] 0 0
Time To Next Treatment (TTNT) for KITE-363 or KITE-753
Timepoint [3] 0 0
Up to 15 years
Secondary outcome [4] 0 0
Complete Response (CR) Rate for KITE-363 or KITE-753
Timepoint [4] 0 0
Up to 15 years
Secondary outcome [5] 0 0
Duration of Response (DOR) for KITE-363 or KITE-753
Timepoint [5] 0 0
Up to 15 years
Secondary outcome [6] 0 0
Progression-Free Survival (PFS) for KITE-363 or KITE-753
Timepoint [6] 0 0
Up to 15 years
Secondary outcome [7] 0 0
Overall Survival (OS) for KITE-363 or KITE-753
Timepoint [7] 0 0
Up to 15 years
Secondary outcome [8] 0 0
Percentage of Participants who Develop Antibodies to KITE-363 or KITE-753 Chimeric Antigen Receptor (CAR) T Cells
Timepoint [8] 0 0
Enrollment; up to 12 months
Secondary outcome [9] 0 0
Levels of KITE-363 or KITE-753 CAR T Cells and Analytes (Including Cytokines) in the Blood
Timepoint [9] 0 0
Up to 15 years
Secondary outcome [10] 0 0
Peak Serum Levels of Key Analytes Homeostatic/Proliferative Cytokines: Interleukin (IL)-2, IL-7, and IL-15
Timepoint [10] 0 0
Up to 3 months
Secondary outcome [11] 0 0
Peak Serum Levels of Key Analytes Inflammatory/Immune Modulating Cytokines: IFN-?, IL-6, IL-10, IL-17, IL-1RA, Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF), and Tumor Necrosis Factor-Alpha (TNF-a)
Timepoint [11] 0 0
Up to 3 months
Secondary outcome [12] 0 0
Peak Serum Levels of Key Analytes Correlates of Acute Phase Response: C-Reactive Protein (CRP)
Timepoint [12] 0 0
Up to 3 months
Secondary outcome [13] 0 0
Peak Serum Levels of Key Analytes Correlates of Acute Phase Response: Ferritin
Timepoint [13] 0 0
Up to 3 months
Secondary outcome [14] 0 0
Peak Serum Levels of Key Analytes Correlates of Acute Phase Response: Soluble IL-2 Receptor Alpha (Sil-2Ra)
Timepoint [14] 0 0
Up to 3 months
Secondary outcome [15] 0 0
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)
Timepoint [15] 0 0
Up to 3 months
Secondary outcome [16] 0 0
Peak Serum Levels of Key Analytes Immune-Effector Molecules: Perforin, Granzyme A, and Granzyme B
Timepoint [16] 0 0
Up to 3 months

Eligibility
Key inclusion criteria
Key

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

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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 design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/10/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2026
Actual
Sample size
Target
114
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Virginia
Country [10] 0 0
Germany
State/province [10] 0 0
Wuerzburg
Country [11] 0 0
Netherlands
State/province [11] 0 0
Amsterdam
Country [12] 0 0
United Kingdom
State/province [12] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Kite, A Gilead Company
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04989803
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Kite Study Director
Address 0 0
Kite, A Gilead Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Medical Information
Address 0 0
Country 0 0
Phone 0 0
844-454-5483(1-844-454-KITE)
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04989803