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Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Utomilumab in Adults With Refractory Large B-cell Lymphoma (ZUMA-11)

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: NCT03704298
Recruitment Status : Recruiting
First Posted : October 12, 2018
Last Update Posted : September 28, 2020
Information provided by (Responsible Party):
Gilead Sciences ( Kite, A Gilead Company )

Brief Summary:

The primary objectives of this study are:

Phase 1: To evaluate the safety of axicabtagene ciloleucel in combination with utomilumab and to identify the most appropriate dose and timing of utomilumab to carry forward into Phase 2

Phase 2: To evaluate the efficacy of axicabtagene ciloleucel and utomilumab in participants with refractory large B-cell lymphoma

Condition or disease Intervention/treatment Phase
Relapsed/Refractory Large B-cell Lymphoma Drug: Cyclophosphamide Drug: Fludarabine Biological: Axicabtagene Ciloleucel Biological: Utomilumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: N/A
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 Axicabtagene Ciloleucel in Combination With Utomilumab in Subjects With Relapsed/Refractory Large B-Cell Lymphoma
Actual Study Start Date : November 20, 2018
Estimated Primary Completion Date : February 2022
Estimated Study Completion Date : February 2036

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Axicabtagene ciloleucel plus utomilumab

Phase 1: Participants will receive cyclophosphamide and fludarabine conditioning chemotherapy followed by axicabtagene ciloleucel treatment on Day 0 plus utomilumab on study Day 1 or study Day 21 and continuing once every 4 weeks (Q4W) for 6 months or until Progressive Disease, whichever comes first.

Phase 2: Participants will receive cyclophosphamide and fludarabine conditioning chemotherapy followed by axicabtagene ciloleucel and utomilumab based on the dose/regimen selected to move forward from the Phase 1 portion of the study as recommended by the internal Safety Review Team.

Drug: Cyclophosphamide
Administered according to package insert

Drug: Fludarabine
Administered according to package insert

Biological: Axicabtagene Ciloleucel
A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously
Other Name: Yescarta®

Biological: Utomilumab
Administered as an IV infusion

Primary Outcome Measures :
  1. For Phase 1: Percentage of Participants Experiencing Adverse Events defined as Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 28 days ]
    Dose-limiting toxicity is defined as protocol-defined axicabtagene ciloleucel related events with onset within the first 28 days following axicabtagene ciloleucel infusion.

  2. For Phase 2: Complete Response Rate [ Time Frame: Up to 1 year ]
    Complete response rate is defined as the incidence of a complete response per the Lugano Classification (Cheson et al, 2014), as determined by study investigators.

Secondary Outcome Measures :
  1. For Phase 1 and Phase 2: Objective Response Rate [ Time Frame: Up to 15 years ]
    Objective response rate is defined as the incidence of either a complete response (CR) or a partial response (PR) per Lugano Classification as determined by study investigators.

  2. For Phase 1 and Phase 2: Duration of Response [ Time Frame: Up to 15 years ]
    Among participants who experience an objective response, duration of response is defined as the date of their first objective response to disease progression per Lugano Classification as determined by study investigators or death from any cause.

  3. For Phase 1 and Phase 2: Progression Free Survival [ Time Frame: Up to 15 years ]
    Progression free survival is defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression per Lugano Classification as determined by study investigators or death from any cause.

  4. For Phase 1 and Phase 2: Overall Survival [ Time Frame: Up to 15 years ]
    Overall survival is defined as the time from axicabtagene ciloleucel infusion to the date of death.

  5. For Phase 1 and Phase 2: Percentage of Participants Experiencing Adverse Events [ Time Frame: Up to 24 months plus 30 days ]
  6. For Phase 1 and Phase 2: Percentage of Participants Experiencing Clinically Significant Changes in Safety Lab Values [ Time Frame: Up to 24 months plus 30 days ]
  7. For Phase 1 and Phase 2: Pharmacokinetics: Levels of Axicabtagene Ciloleucel in Blood [ Time Frame: Up to 2 years ]
  8. For Phase 1 and Phase 2: Pharmacodynamics: Levels of Cytokines in Serum [ Time Frame: Up to 2 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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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:

  • Histologically proven large B-cell lymphoma including the following types:

    • Diffuse large B cell lymphoma (DLBCL) not otherwise specified (ABC/GCB)
    • High grade B-cell lymphoma (HGBCL) with or without MYC and BCL2 and/or BCL6 rearrangement
    • DLBCL arising from follicular lymphoma
    • T cell/histiocyte rich large B-cell lymphoma
    • DLBCL associated with chronic inflammation
    • Primary cutaneous DLBCL, leg type
    • Epstein-Barr virus (EBV) + DLBCL
  • Relapsed or chemotherapy-refractory disease, defined as one or more of the following:

    • No response to first-line therapy (primary refractory disease); subjects who are intolerant to first-line systemic chemotherapy are excluded

      • Progressive disease (PD) as best response to first-line therapy
      • Stable disease (SD) as best response after at least 4 cycles of first-line therapy (eg, 4 cycles of R-CHOP) with SD duration no longer than 6 months from last dose of therapy
    • No response to second or greater lines of therapy

      • PD as best response to most recent therapy regimen
      • SD as best response after at least 2 cycles of last line of therapy with SD duration no longer than 6 months from last dose of therapy OR
    • Refractory post-autologous stem cell transplant (ASCT)

      • Disease progression or relapsed . 12 months after ASCT (must have biopsy proven recurrence in relapsed participant)
      • if salvage therapy is given post-ASCT, the participant must have had no response to or relapsed after the last line of therapy
    • Relapsed or refractory LBCL including DLBCL, TFL, and HGBCL after 2 or more lines of systemic therapy that is defined by and aligns with currently approved indication:

      • Relapsed disease after 2 or more lines of systemic therapy
      • Best response that is less than a CR to second or greater line of systemic therapy
  • At least 1 measureable lesion according to the Lugano Classification (Cheson et al, 2014). Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
  • Participant 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
  • No radiographic evidence, suspicion and/or history of central nervous system (CNS) involvement of lymphoma
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Absolute neutrophil count (ANC) ≥ 1000/μL
  • Platelet count ≥ 75,000/μL
  • Absolute lymphocyte count ≥ 100/μL
  • Adequate renal, hepatic, pulmonary, and cardiac function defined as:

    • Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min
    • Serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤ 2.5 upper limit of normal (ULN)
    • Total bilirubin ≤ 1.5 mg/dL, except in individuals with Gilbert's syndrome.
    • Cardiac ejection fraction ≥ 50% and no evidence of pericardial effusion within 180 days provided the subject did not receive an anthracycline-based treatment or experience a cardiac event or change in performance status
    • No clinically significant pleural effusion
    • Baseline oxygen saturation > 92% on room air

Key Exclusion Criteria:

  • Histologically proven primary mediastinal B-cell lymphoma (PMBCL)
  • History of Richter's transformation of chronic lymphocytic lymphoma (CLL)
  • Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy
  • History of severe, immediate hypersensitivity reaction attributed to aminoglycosides
  • History of HIV infection or acute or chronic active hepatitis B or C infection. Individuals with history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America (IDSA) guidelines or applicable country guidelines
  • Individuals with detectable cerebrospinal fluid malignant cells, brain metastases, or a history of CNS lymphoma
  • History or presence of CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
  • Individuals with cardiac atrial or cardiac ventricular lymphoma involvement
  • History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
  • Requirement for urgent therapy due to tumor mass effects (eg, blood vessel compression, bowel obstruction, or transmural gastric involvement
  • Primary immunodeficiency
  • History of autoimmune disease (eg, Crohn's, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years. 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
  • History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment
  • Any medical condition likely to interfere with assessment of safety or efficacy of study treatment
  • Autologous stem cell transplant within 6 weeks of planned enrollment
  • Prior organ transplantation including prior allogeneic stem cell transplant (SCT)
  • Use of any standard or experimental anti-cancer therapy within 2 weeks prior to enrollment, including cytoreductive therapy and radiotherapy, immunotherapy, or cytokine therapy (except for erythropoietin) Prior treatment with PD-L1 inhibitor, PD-1 inhibitor, anti-CTLA4, anti-CD137 (4-1BB), anti-OX40 or other immune checkpoint blockade or activator therapy
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (eg, 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
  • In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.

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 identifier (NCT number): NCT03704298

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Contact: Medical Information 1-844-454-5483(1-844-454-KITE)

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United States, California
Stanford Cancer Institute Recruiting
Palo Alto, California, United States, 94305
Contact: Claire Sharan    650-721-4091   
Principal Investigator: David Miklos, MD         
UCLA Hematology/ Oncology Recruiting
Santa Monica, California, United States, 90404
Contact: Ana Crosetti    310-825-7412   
Principal Investigator: John Timmerman, MD         
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Joseph Boyd    813-745-4201   
Principal Investigator: Jain Michael, MD         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Michael Rocchio    617-632-5221    MichaelJ_Rocchio@DFCI.HARVARD.EDU   
Principal Investigator: Caron Jacobson, MD         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Julia Gould    212-305-6361      
Principal Investigator: Ran Reshef, MD         
Sponsors and Collaborators
Kite, A Gilead Company
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Study Director: Kite Study Director Kite, A Gilead Company
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Responsible Party: Kite, A Gilead Company Identifier: NCT03704298    
Other Study ID Numbers: KTE-C19-111
First Posted: October 12, 2018    Key Record Dates
Last Update Posted: September 28, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists