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Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Either Rituximab or Lenalidomide in Participants With Refractory Large B-Cell Lymphoma (ZUMA-14)

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ClinicalTrials.gov Identifier: NCT04002401
Recruitment Status : Not yet recruiting
First Posted : June 28, 2019
Last Update Posted : September 23, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:
The primary objective of this study is to estimate the efficacy of axicabtagene ciloleucel in combination with either rituximab or lenalidomide, as measured by assessment of response rates in adult participants with relapsed/refractory large B-cell lymphoma.

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

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Either Rituximab or Lenalidomide in Subjects With Refractory Large B-Cell Lymphoma (ZUMA-14)
Estimated Study Start Date : October 2019
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : June 2035


Arm Intervention/treatment
Experimental: Axicabtagene Ciloleucel and Rituximab Combination
Participants will receive rituximab, and fludarabine and cyclophosphamide conditioning chemotherapy, followed by axicabtagene ciloleucel and additional rituximab.
Biological: Axicabtagene Ciloleucel
A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously
Other Name: Yescarta®

Drug: Rituximab
Administered intravenously
Other Name: RITUXAN®

Drug: Fludarabine
Administered according to package insert

Drug: Cyclophosphamide
Administered according to package insert

Experimental: Axicabtagene Ciloleucel and Lenalidomide Combination
Participants will receive lenalidomide, and fludarabine and cyclophosphamide conditioning chemotherapy, followed by axicabtagene ciloleucel and additional lenalidomide.
Biological: Axicabtagene Ciloleucel
A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously
Other Name: Yescarta®

Drug: Lenalidomide
Capsule(s) administered orally with or without food
Other Name: REVLIMID®

Drug: Fludarabine
Administered according to package insert

Drug: Cyclophosphamide
Administered according to package insert




Primary Outcome Measures :
  1. Complete Response (CR) Rate [ Time Frame: Up to 2 years ]
    CR rate is defined as the incidence of a CR per the Lugano Classification as determined by study investigators.


Secondary Outcome Measures :
  1. Percentage of Participants Experiencing Adverse Events and Clinically Significant Changes in Safety Lab Values [ Time Frame: Up to 15 years ]
  2. Objective Response Rate (ORR) [ Time Frame: Time Frame: Up to 2 years ]
    ORR is defined as the incidence of either a CR or a partial response (PR) per the Lugano Classification as determined by study investigators.

  3. Duration of Response (DOR) [ Time Frame: Up to 2 years ]
    DOR is defined only for participants who experience an objective response and is the time from the first objective response to disease progression per the Lugano Classification as determined by study investigators or death from any cause.

  4. Progression-Free Survival (PFS) [ Time Frame: Up to 2 years ]
    PFS 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.

  5. Overall Survival (OS) [ Time Frame: Up to 15 years ]
    OS is defined as the time from axicabtagene ciloleucel infusion to the date of death.

  6. Levels of Axicabtagene Ciloleucel in Blood [ 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:

  • Histologically confirmed large B-cell lymphoma
  • Chemotherapy-refractory disease, defined as one or more of the following:

    • No response to first-line therapy (primary refractory disease)
    • No response to second or greater lines of therapy OR
    • Refractory after autologous stem cell transplant (ASCT)
  • At least 1 measureable lesion according to the Lugano Classification (Cheson 2014).
  • Individuals must have received adequate prior therapy, including at a minimum:

    • Anti-CD20 monoclonal antibody
    • An anthracycline-containing chemotherapy regimen
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function
  • Individuals must be able to comply with the requirements of REVLIMID Risk Evaluation and Mitigation Strategy (REMS)®

Key Exclusion Criteria:

  • Known CD19 negative or CD20 negative tumor
  • History of Richter's transformation of Chronic Lymphocytic Leukemia (CLL)
  • Prior lenalidomide or other immunomodulatory imide drug (IMiD) treatment
  • Prior CAR therapy or other genetically modified T-cell therapy
  • Prior organ transplantation including prior allogeneic stem cell transplant (SCT)
  • Prior CD19 targeted therapy
  • Clinically significant infection or cardiopulmonary disease
  • Presence of any in-dwelling lines or drains (dedicated central venous access catheters allowed)
  • History or presence of central nervous system (CNS) lymphoma or nonmalignant CNS disorder or cerebrospinal fluid (CSF) malignant cells or brain metastases
  • History of autoimmune disease
  • History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the last year

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): NCT04002401


Contacts
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Contact: Medical Information 1-844-454-5483(1-844-454-KITE) medinfo@kitepharma.com

Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Kite Study Director Kite, A Gilead Company

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT04002401     History of Changes
Other Study ID Numbers: KT-US-471-0114
First Posted: June 28, 2019    Key Record Dates
Last Update Posted: September 23, 2019
Last Verified: September 2019
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
Lenalidomide
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Rituximab
Fludarabine
Fludarabine phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites