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Safety and Efficacy of KTE-C19 in Combination With Atezolizumab in Adults With Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (ZUMA-6)

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ClinicalTrials.gov Identifier: NCT02926833
Recruitment Status : Active, not recruiting
First Posted : October 6, 2016
Last Update Posted : February 28, 2019
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Gilead Sciences ( Kite, A Gilead Company )

Brief Summary:
The primary objective of phase 1 is to evaluate the safety of axicabtagene ciloleucel and atezolizumab combination regimens. The primary objective of phase 2 is to evaluate the efficacy of axicabtagene ciloleucel and atezolizumab, as measured by complete response rate in subjects with refractory diffuse large B-cell lymphoma (DLBCL).

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 37 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)
Actual Study Start Date : September 2016
Actual Primary Completion Date : February 14, 2019
Estimated Study Completion Date : August 2033


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

Biological: atezolizumab (anti-PD-L1)
Administered intravenously

Drug: Cyclophosphamide
Administered intravenously

Drug: Fludarabine
Administered intravenously




Primary Outcome Measures :
  1. Phase 1: Percentage of participants experiencing adverse events defined as dose-limiting toxicities [ Time Frame: 21 days from 1st dose of atezolizumab ]
    Dose-limiting toxicity is defined as protocol-defined KTE-C19-related or atezolizumab-related events with an onset immediately after and through 21 days following the first atezolizumab infusion.

  2. Phase 2: Complete Response Rate [ Time Frame: 5 years ]
    Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma


Secondary Outcome Measures :
  1. Phase 1 and 2: Objective response rate (complete response [CR] + partial response [PR]) [ Time Frame: 5 years ]
    Objective Response Rate is defined as the incidence of either a complete response or a partial response by the revised IWG Response Criteria for Malignant Lymphoma as determined by the study investigators.

  2. Phase 1 and 2: Duration of Response [ Time Frame: 5 years ]
    Duration of Response for participants who experience an objective response is defined as the date of their first objective response (which is subsequently confirmed) to disease progression per the revised IWG Response Criteria for Malignant Lymphoma or death regardless of cause.

  3. Phase 1 and 2: Progression Free Survival [ Time Frame: 5 years ]
    Progression Free Survival is defined as the time from the KTE-C19 infusion date to the date of disease progression per the revised IWG Response Criteria for Malignant Lymphoma or death from any cause.

  4. Phase 1 and 2: Overall Survival [ Time Frame: 5 years ]
    Overall Survival is defined as the time from KTE-C19 infusion to the date of death.

  5. Phase 1 and 2: Percentage of participants experiencing adverse events [ Time Frame: Up to 5 years ]
  6. Phase 1 and 2: Percentage of participants experiencing clinically significant changes in safety lab values [ Time Frame: Up to 5 years ]
  7. Phase 1 and 2: Levels of axicabtagene ciloleucel in blood [ Time Frame: Up to 2 years ]
  8. Phase 1 and 2: Percentage of participants with anti-KTE-C19 antibodies [ Time Frame: Up to 2 years ]
  9. Phase 1 and 2:Percentage of participants with anti- atezolizumab antibodies in serum [ Time Frame: Up to 2 years ]
  10. Phase 1 and 2: Levels of atezolizumab in serum [ Time Frame: Up to 2 years ]
  11. Phase 1 and 2: Levels of cytokines and other markers in serum [ Time Frame: Up to 2 years ]


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
Criteria

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 stem cell transplantation (SCT)
  3. Individuals 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 Individuals 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. 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 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 Individuals who received atezolizumab in this study and are eligible for re-treatment
  11. Prior CD19 targeted therapy

Note: Other protocol defined Inclusion/Exclusion criteria may apply


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 ClinicalTrials.gov identifier (NCT number): NCT02926833


Locations
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United States, California
City of Hope
Duarte, California, United States, 91010
Stanford Cancer Center
Stanford, California, United States, 94305
United States, Florida
H Lee Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Kite, A Gilead Company
Genentech, Inc.
Investigators
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Study Director: Kite Study Director Kite, A Gilead Company

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Responsible Party: Kite, A Gilead Company
ClinicalTrials.gov Identifier: NCT02926833     History of Changes
Other Study ID Numbers: KTE-C19-106
First Posted: October 6, 2016    Key Record Dates
Last Update Posted: February 28, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Atezolizumab
Antibodies, Monoclonal
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites