Study of Safety and Efficacy of KTE-C19 in Combination With Atezolizumab in Adults With Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

NCT ID: NCT02926833

Last Updated: 2024-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-29
• Study Completion Date: 2023-01-12

Brief Summary

The primary objective of phase 1 is to evaluate the safety of KTE-C19 and atezolizumab combination regimens.

The primary objective of phase 2 is to evaluate the efficacy of KTE-C19 and atezolizumab, as measured by complete response rate in participants with refractory diffuse large B-cell lymphoma (DLBCL).

Participants who received an infusion of KTE-C19 will complete the remainder of the 15 year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968 (NCT05041309).

Conditions

Refractory Diffuse Large B Cell Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1 Cohort 1: KTE-C19 + ATZ (After 21 Days of KTE-C19)

Participants received conditioning chemotherapy consisting of 30 mg/m\^2 fludarabine and 500 mg/m\^2 cyclophosphamide intravenous (IV) infusion per day for 3 days followed by KTE-C19 IV infusion at a target dose of 2 x 10\^6 anti-CD19 chimeric antigen receptor (CAR) T cells/kg followed by 4 doses of atezolizumab (ATZ) (1200 mg/dose) IV infusion every 21 days, beginning 21 days following KTE-C19.

Group Type: EXPERIMENTAL

KTE-C19

Intervention Type: BIOLOGICAL

A single infusion of KTE-C19 CAR-T cells administered intravenously

Atezolizumab

Intervention Type: BIOLOGICAL

Administered intravenously

Cyclophosphamide

Intervention Type: DRUG

Administered intravenously

Fludarabine

Intervention Type: DRUG

Administered intravenously

Phase 1 Cohort 2: KTE-C19 + ATZ (After 14 Days of KTE-C19)

Participants received conditioning chemotherapy consisting of 30 mg/m\^2 fludarabine and 500 mg/m\^2 cyclophosphamide IV infusion per day for 3 days followed by KTE-C19 IV infusion at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg followed by 4 doses of ATZ (1200 mg/dose) IV infusion every 21 days, beginning 14 days following KTE-C19.

Group Type: EXPERIMENTAL

KTE-C19

Intervention Type: BIOLOGICAL

A single infusion of KTE-C19 CAR-T cells administered intravenously

Atezolizumab

Intervention Type: BIOLOGICAL

Administered intravenously

Cyclophosphamide

Intervention Type: DRUG

Administered intravenously

Fludarabine

Intervention Type: DRUG

Administered intravenously

Phase 1 Cohort 3: KTE-C19 + ATZ (After 1 Day of KTE-C19)

Participants received conditioning chemotherapy consisting of 30 mg/m\^2 fludarabine and 500 mg/m\^2 cyclophosphamide IV infusion per day for 3 days followed by KTE-C19 IV infusion at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg followed by 4 doses of ATZ (1200 mg/dose) IV infusion every 21 days, beginning 1 day following KTE-C19.

Group Type: EXPERIMENTAL

KTE-C19

Intervention Type: BIOLOGICAL

A single infusion of KTE-C19 CAR-T cells administered intravenously

Atezolizumab

Intervention Type: BIOLOGICAL

Administered intravenously

Cyclophosphamide

Intervention Type: DRUG

Administered intravenously

Fludarabine

Intervention Type: DRUG

Administered intravenously

Phase 2: KTE-C19 + ATZ (After 1 Day of KTE-C19)

Participants received conditioning chemotherapy consisting of 30 mg/m\^2 fludarabine and 500 mg/m\^2 cyclophosphamide IV infusion per day for 3 days followed by KTE-C19 IV infusion at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg followed by 4 doses of ATZ (1200 mg/dose) IV infusion every 21 days, beginning 1 day following KTE-C19.

Group Type: EXPERIMENTAL

KTE-C19

Intervention Type: BIOLOGICAL

A single infusion of KTE-C19 CAR-T cells administered intravenously

Atezolizumab

Intervention Type: BIOLOGICAL

Administered intravenously

Cyclophosphamide

Intervention Type: DRUG

Administered intravenously

Fludarabine

Intervention Type: DRUG

Administered intravenously

Interventions

KTE-C19

A single infusion of KTE-C19 CAR-T cells administered intravenously

Intervention Type: BIOLOGICAL

Atezolizumab

Administered intravenously

Intervention Type: BIOLOGICAL

Cyclophosphamide

Administered intravenously

Intervention Type: DRUG

Fludarabine

Administered intravenously

Intervention Type: DRUG

Other Intervention Names

Axicabtagene ciloleucel; Yescarta®

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed DLBCL

2. Chemotherapy-refractory disease, defined as one or more of the following:

• Stable disease (duration of stable disease must be less than or equal to 6 months) or progressive disease as best response to most recent chemotherapy containing regimen
• Disease progression or recurrence less than or equal to 12 months of prior autologous stem cell transplantation (SCT)

3. Individuals must have received adequate prior therapy including at a minimum:

• Anti-cluster of differentiate 20 (anti-CD20) monoclonal antibody unless investigator determines that tumor is CD20-negative; and
• an anthracycline containing chemotherapy regimen

4. At least one measurable lesion per revised International Working Group (IWG) Response Criteria

5. Age 18 years or older

6. Eastern cooperative oncology group (ECOG) performance status of 0 or 1

7. Adequate organ and bone marrow function

8. All individuals or legally appointed representatives/caregivers, must personally sign and date the institutional review board (IRB)/independent ethics committee (IEC) approved consent form before initiating any study specific procedures or activities.

Exclusion Criteria

1. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast) or follicular lymphoma unless disease free for at least 3 years

2. History of allogeneic stem cell transplantation

3. Prior CAR therapy or other genetically modified T cell therapy

4. Clinically significant active infection

5. Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive)

6. Individuals with detectable cerebrospinal fluid malignant cells or brain metastases or with a history of cerebrospinal fluid malignant cells or brain metastases

7. History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with central nervous system (CNS) involvement

8. History of autoimmune disease. Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone and participants with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible for this study.

9. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis per chest computed tomography (CT) scan at screening. History of radiation pneumonitis in the radiation field (fibrosis) is allowed.

10. Prior treatment with Programmed Cell Death Ligand 1 (PD-L1) inhibitor, PD-1 inhibitor, anti-CTLA4, anti-CD137, anti-OX40 or other immune checkpoint blockade or activator therapy with the exception of Individuals who received atezolizumab in this study and are eligible for re-treatment

11. Prior CD19 targeted therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Kite, A Gilead Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kite Study Director

Role: STUDY_DIRECTOR

Kite, A Gilead Company

Locations

City of Hope

Duarte, California, United States

Stanford Cancer Center

Palo Alto, California, United States

H Lee Moffitt Cancer Center

Tampa, Florida, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

Jacobson CA, Locke FL, Miklos DB, Herrera AF, Westin JR, Lee J, et al. End of Phase 1 results for ZUMA-6: Axicabtagene ciloleucel (axi-cel) in combination with atezolizumab for the treatment of patients with refractory diffuse large B cell lymphoma. Presented at ASH, 2018.

Reference Type: BACKGROUND

Locke FL, Westin JR, Miklos DB, Herrera AF, Jacobson CA, Lee J, et al. Phase 1 results from ZUMA-6: Axicabtagene ciloleucel (axi-cel; KTE-C19) in combination with atezolizumab for the treatment of patients with refractory diffuse large B cell lymphoma. Presented at ASH, 2018, presentation #2628.

Reference Type: BACKGROUND

Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

Reference Type: DERIVED

PMID: 34515338 (View on PubMed)

Provided Documents

Document Type: Study Protocol: Amendment 1

View Document

Document Type: Study Protocol: Amendment 2

View Document

Document Type: Statistical Analysis Plan: Statistical Analysis Plan: Original

View Document

Document Type: Statistical Analysis Plan: Supplemental Statistical Analysis Plan

View Document

Related Links

https://www.gileadclinicaltrials.com/study/?id=KTE-C19-106

Gilead Clinical Trials Website

Other Identifiers

KTE-C19-106

Identifier Type: -

Identifier Source: org_study_id