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

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ClinicalTrials.gov Identifier: NCT02348216
Recruitment Status : Recruiting
First Posted : January 28, 2015
Last Update Posted : December 4, 2018
Sponsor:
Information provided by (Responsible Party):
Kite, A Gilead Company

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, and Cohort 5).

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 and tumor debulking therapy on the rate and severity of cytokine release syndrome (CRS) and neurologic toxicity

Condition or disease Intervention/treatment Phase
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) Biological: Axicabtagene Ciloleucel Drug: Fludarabine Drug: Cyclophosphamide Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Multicenter Study Evaluating the Safety and Efficacy of KTE-C19 in Adults With Refractory Aggressive Non-Hodgkin Lymphoma
Actual Study Start Date : January 2015
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : October 2034


Arm Intervention/treatment
Experimental: Axicabtagene Ciloleucel
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, axicabtagene ciloleucel.
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




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. Phase 2 Safety Management Study: Incidence and Severity of CRS and Neurologic Toxicities [ Time Frame: Up to 12 months ]

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Overall Survival (OS) [ Time Frame: Up to 24 months ]
    OS is defined as the time from axicabtagene ciloleucel infusion to the date of death.

  6. Percentage of Participants Experiencing Adverse Events [ Time Frame: Up to 12 months ]
  7. Percentage of Participants Experiencing Clinically Significant Changes in Safety Lab Values [ Time Frame: Up to 12 months ]
  8. Percentage of Participants with Anti-Axicabtagene Ciloleucel Antibodies [ Time Frame: Up to 12 months ]
  9. Pharmacokinetics (Levels of Anti-CD19 CAR T Cells in Blood) [ Time Frame: Up to 2 years ]
  10. Pharmacodynamics (Levels of Cytokines in Serum) [ Time Frame: Up to 12 months ]
  11. 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.

  12. 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.

  13. Phase 2 Safety Management Study: Changes Over Time in the Visual Analogue Scale (VAS) Score [ Time Frame: Up to 5 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)
    • 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 individuals with transformed FL must have received prior chemotherapy for follicular lymphoma and subsequently 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.

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.


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): NCT02348216


Contacts
Contact: Medical Information 844-454-KITE medinfo@kitepharma.com

  Show 36 Study Locations
Sponsors and Collaborators
Kite, A Gilead Company
Investigators
Study Director: Kite Study Director Kite, A Gilead Company

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Kite, A Gilead Company
ClinicalTrials.gov Identifier: NCT02348216     History of Changes
Other Study ID Numbers: KTE-C19-101
First Posted: January 28, 2015    Key Record Dates
Last Update Posted: December 4, 2018
Last Verified: November 2018

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

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Fludarabine phosphate
Fludarabine
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