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Safety and Efficacy of KTE-C19 in Adults With Refractory Aggressive Non-Hodgkin Lymphoma (ZUMA-1)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02348216
Recruitment Status : Active, not recruiting
First Posted : January 28, 2015
Last Update Posted : September 15, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences ( Kite, A Gilead Company )

Tracking Information
First Submitted Date  ICMJE January 22, 2015
First Posted Date  ICMJE January 28, 2015
Last Update Posted Date September 15, 2020
Actual Study Start Date  ICMJE January 2015
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 30, 2018)
  • Phase 1 Study: Percentage of Participants Experiencing Adverse Events defined as Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 30 Days ]
    Dose-limiting toxicity is defined as protocol-defined axicabtagene ciloleucel related events with onset within the first 30 days following axicabtagene ciloleucel infusion.
  • Phase 2 Pivotal Study: Overall Response Rate (ORR) [ Time Frame: Up to 12 months ]
    ORR is defined as the incidence of either a complete response (CR) or a partial response (PR) per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma as determined by the study investigators.
  • Phase 2 Safety Management Study: Incidence and Severity of CRS and Neurologic Toxicities [ Time Frame: Up to 12 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 27, 2015)
  • 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)
  • Phase 2: Overall Response Rate [ Time Frame: 12 Months ]
    Objective response rate (complete response [CR] + partial response [PR]) per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 30, 2018)
  • Duration of Response (DOR) [ Time Frame: Up to 12 months ]
    Among participants who experience an objective response, DOR 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.
  • Phase 1 Study: ORR [ Time Frame: Up to 12 months ]
    ORR is defined as the incidence of either a complete response (CR) or a partial response (PR) per the revised IWG Response Criteria for Malignant Lymphoma as determined as determined by the study investigators.
  • Phase 2 Study: ORR per Independent Radiological Review Committee (IRRC) [ Time Frame: Up to 12 months ]
    ORR is defined as the incidence of either a complete response (CR) or a partial response (PR) per the IRRC.
  • Progression-Free Survival (PFS) [ Time Frame: Up to 12 months ]
    PFS is defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression per the revised IWG Response Criteria for Malignant Lymphoma or death from any cause.
  • Overall Survival (OS) [ Time Frame: Up to 24 months ]
    OS is defined as the time from axicabtagene ciloleucel infusion to the date of death.
  • Percentage of Participants Experiencing Adverse Events [ Time Frame: Up to 12 months ]
  • Percentage of Participants Experiencing Clinically Significant Changes in Safety Lab Values [ Time Frame: Up to 12 months ]
  • Percentage of Participants with Anti-Axicabtagene Ciloleucel Antibodies [ Time Frame: Up to 12 months ]
  • Pharmacokinetics (Levels of Anti-CD19 CAR T Cells in Blood) [ Time Frame: Up to 2 years ]
  • Pharmacodynamics (Levels of Cytokines in Serum) [ Time Frame: Up to 12 months ]
  • Phase 2 Safety Management Study: ORR [ Time Frame: Up to 12 months ]
    ORR is defined as the incidence of either a complete response (CR) or a partial response (PR) per the revised IWG Response Criteria for Malignant Lymphoma as determined by study investigators.
  • Phase 2 Safety Management Study: Changes Over Time in the European Quality of Life Five Dimension Five Level Scale (EQ-5D) [ Time Frame: Up to 5 years ]
    The European Quality of Life Five Dimension Five Level Scale (EQ-5D) is a generic measure of health status that provides a simple descriptive profile and a single index value.
  • Phase 2 Safety Management Study: Changes Over Time in the Visual Analogue Scale (VAS) Score [ Time Frame: Up to 5 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 27, 2015)
  • Duration of Response [ Time Frame: 12 Months ]
  • Progression Free Survival [ Time Frame: 12 Months ]
  • Overall Survival [ Time Frame: 12 Months ]
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of KTE-C19 in Adults With Refractory Aggressive Non-Hodgkin Lymphoma
Official Title  ICMJE A Phase 1/2 Multicenter Study Evaluating the Safety and Efficacy of KTE-C19 in Adults With Refractory Aggressive Non-Hodgkin Lymphoma
Brief Summary

This study will be separated into 3 distinct phases designated as the Phase 1 study, Phase 2 pivotal study (Cohort 1 and Cohort 2), and Phase 2 safety management study (Cohort 3 and Cohort 4, Cohort 5 and Cohort 6).

The primary objectives of this study are:

  • Phase 1 Study: Evaluate the safety of axicabtagene ciloleucel regimens
  • Phase 2 Pivotal Study; Evaluate the efficacy of axicabtagene ciloleucel
  • Phase 2 Safety Management Study: Assess the impact of prophylactic regimens or earlier interventions on the rate and severity of cytokine release syndrome (CRS) and neurologic toxicities
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Refractory Diffuse Large B Cell Lymphoma (DLBCL)
  • Relapsed Diffuse Large B-Cell Lymphoma
  • Transformed Follicular Lymphoma (TFL)
  • Primary Mediastinal B-cell Lymphoma (PMBCL)
  • High Grade B-cell Lymphoma (HGBCL)
Intervention  ICMJE
  • Biological: Axicabtagene Ciloleucel
    A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg.
    Other Name: Yescarta®
  • Drug: Fludarabine
    Administered according to package insert
  • Drug: Cyclophosphamide
    Administered according to package insert
Study Arms  ICMJE Experimental: Axicabtagene Ciloleucel
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, axicabtagene ciloleucel.
Interventions:
  • Biological: Axicabtagene Ciloleucel
  • Drug: Fludarabine
  • Drug: Cyclophosphamide
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 31, 2020)
307
Original Estimated Enrollment  ICMJE
 (submitted: January 27, 2015)
124
Estimated Study Completion Date  ICMJE August 2035
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria

  1. Histologically confirmed:

    • Diffuse Large B Cell Lymphoma (DLBCL)
    • Primary Mediastinal Large B Cell Lymphoma (PMBCL)
    • Transformation Follicular Lymphoma (TFL)
    • High grade B-cell lymphoma (HGBCL)
  2. Chemotherapy-refractory disease, defined as one of more of the following:

    • No response to last line of therapy i. Progressive disease (PD) as best response to most recent therapy regimen ii. Stable disease (SD) as best response to most recent therapy with duration no longer than 6 month from last dose of therapy OR
    • Refractory post-autologous stem cell transplant (ASCT) i. Disease progression or relapsed less than or equal to 12 months of ASCT (must have biopsy proven recurrence in relapsed individuals) ii. If salvage therapy is given post-ASCT, the individual must have had no response to or relapsed after the last line of therapy
  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
    • for individual with transformed FL must have chemorefractory disease after transformation to DLBCL.
  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. Absolute neutrophil count (ANC) ≥ 1000/uL
  8. Absolute lymphocyte count ≥ 100/uL
  9. Platelet count ≥ 75,000/uL
  10. Adequate renal, hepatic, pulmonary and cardiac function defined as:

    • Creatinine clearance (as estimated by Cockcroft Gault) > 60 mL/min
    • Serum alanine aminotransferase (ALT)/aspartate aminotransferase (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%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant pleural effusion
    • Baseline oxygen saturation >92% on room air
  11. 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.
  12. Relapsed or refractory large B-cell lymphoma including DLBCL, PMBCL, TFL, and HGBCL after two systemic lines of therapy

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. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment
  5. 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
  6. Individuals with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of central nervous system (CNS) lymphoma or primary CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases
  7. History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   France,   Germany,   Israel,   Netherlands,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02348216
Other Study ID Numbers  ICMJE KTE-C19-101
2015-005007-86 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and transparency.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: 18 months after study completion
Access Criteria: A secured external environment with username, password, and RSA code.
URL: http://www.gilead.com/research/disclosure-and-transparency
Responsible Party Gilead Sciences ( Kite, A Gilead Company )
Study Sponsor  ICMJE Kite, A Gilead Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Kite Study Director Kite, A Gilead Company
PRS Account Gilead Sciences
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP