A Study Evaluating KTE-C19 in Combination With Atezolizumab in Subjects With Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (ZUMA-6)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02926833
Recruitment Status : Recruiting
First Posted : October 6, 2016
Last Update Posted : April 10, 2018
Genentech, Inc.
Information provided by (Responsible Party):
Kite, A Gilead Company

Brief Summary:
This is a phase 1-2, open-label study in subjects with refractory DLBCL, evaluating the safety and efficacy of axicabtagene ciloleucel, an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy, in combination with atezolizumab, a humanized, monoclonal antibody that binds to PD-L1 and blocks interaction with the PD-1 and B7.1 receptors. The trial will be separated into two distinct phases designated as phase 1 and phase 2.

Condition or disease Intervention/treatment Phase
Refractory Diffuse Large B Cell Lymphoma Biological: axicabtagene ciloleucel Drug: atezolizumab (anti-PD-L1) Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 31 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1-2 Multi-Center Study Evaluating the Safety and Efficacy of KTE-C19 in Combination With Atezolizumab in Subjects With Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Study Start Date : September 2016
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : June 2023

Arm Intervention/treatment
Experimental: Single Arm
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously followed by a limited course of atezolizumab
Biological: axicabtagene ciloleucel
Drug: atezolizumab (anti-PD-L1)

Primary Outcome Measures :
  1. Phase 1: Safety (Incidence of adverse events defined as dose-limiting toxicities (DLT)) [ Time Frame: 30 Days ]
    Incidence of adverse events defined as dose-limiting toxicities (DLT)

  2. Phase 2: Complete Response Rate [ Time Frame: 12 Months ]
    Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma

Secondary Outcome Measures :
  1. Objective response rate (complete response [CR] + partial response [PR]) [ Time Frame: 12 Months ]
  2. Duration of Response [ Time Frame: 12 Months ]
  3. Progression Free Survival [ Time Frame: 12 Months ]
  4. Overall Survival [ Time Frame: 12 Months ]
  5. Safety (Incidence of adverse events and clinically significant changes in safety lab values.) [ Time Frame: 12 Months ]
    Incidence of adverse events and clinically significant changes in safety lab values.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Key Inclusion Criteria:

  1. Histologically confirmed:

    • Diffuse Large B Cell Lymphoma (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 SCT
  3. Subjects must have received adequate prior therapy including at a minimum:

    • 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 IWG Response Criteria
  5. Age 18 or older
  6. Eastern cooperative oncology group (ECOG) performance status of 0 or 1
  7. Adequate organ and bone marrow function
  8. All subjects or legally appointed representatives/caregivers, must personally sign and date the IRB/IEC approved consent form before initiating any study specific procedures or activities.

Key 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 HIV or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive)
  6. Subjects 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 CNS involvement
  8. History of autoimmune disease. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone and patients 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 CT scan at screening. History of radiation pneumonitis in the radiation field (fibrosis) is allowed.
  10. Prior treatment with PD-L1 inhibitor, PD-1 inhibitor, anti-CTLA4, anti-CD137, anti-OX40 or other immune checkpoint blockade or activator therapy with the exception of subjects who received atezolizumab in this study and are eligible for re-treatment
  11. Prior CD19 targeted therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02926833

Contact: Medical Information 844-454-KITE

United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Hormoz Mirshkarlo   
Stanford Cancer Center Recruiting
Stanford, California, United States, 94305
Contact: Juliana K Craig   
United States, Florida
H Lee Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Matthew Scott   
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Guadalupe De Maeyer   
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Sherry Adkins   
Sponsors and Collaborators
Kite, A Gilead Company
Genentech, Inc.
Study Director: Mauro Avanzi, M.D., Ph.D. Kite, A Gilead Company

Responsible Party: Kite, A Gilead Company Identifier: NCT02926833     History of Changes
Other Study ID Numbers: KTE-C19-106
First Posted: October 6, 2016    Key Record Dates
Last Update Posted: April 10, 2018
Last Verified: April 2018

Additional relevant MeSH terms:
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs