A Phase 1-2 Multi-Center Study Evaluating Axicabtagene Ciloleucel in Subjects With Refractory Aggressive Non-Hodgkin Lymphoma (ZUMA-1) (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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02348216
Recruitment Status : Recruiting
First Posted : January 28, 2015
Last Update Posted : July 24, 2018
Information provided by (Responsible Party):
Kite, A Gilead Company

Brief Summary:
This is a single arm, open-label, multi-center, phase 1/2 study, to determine the safety and efficacy of KTE-C19, an autologous anti-CD19 chimeric antigen receptor (CAR)-positive T cell therapy, in refractory aggressive Non-Hodgkin Lymphoma (NHL).

Condition or disease Intervention/treatment Phase
Refractory Diffuse Large B Cell Lymphoma Refractory Primary Mediastinal B Cell Lymphoma Refractory Transformed Follicular Lymphoma Relapsed/Refractory Transplant Ineligible Diffuse Large B Cell Lymphoma Relapsed/Refractory Transplant Ineligible Primary Mediastinal B Cell Lymphoma Relapsed/Refractory Transplant Ineligible Transformed Follicular Lymphoma Relapsed/Refractory Large B Cell Lymphoma Including DLBCL, PMBCL, TFL and HGBCL After Two Systemic Lines of Therapy" in Phase 2 Expanded Cohorts Biological: axicabtagene ciloleucel Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 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 Subjects With Refractory Aggressive Non-Hodgkin Lymphoma (ZUMA-1)
Actual Study Start Date : January 2015
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : March 2032

Arm Intervention/treatment
Experimental: Single Arm
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg
Biological: axicabtagene ciloleucel

Primary Outcome Measures :
  1. 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)

  2. 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

  3. Phase 2 Expanded Cohorts: Safety [ Time Frame: 12 Months ]
    Rate and severity of CRS and neurologic toxicities

Secondary Outcome Measures :
  1. Duration of Response [ Time Frame: 12 Months ]
  2. Progression Free Survival [ Time Frame: 12 Months ]
  3. Overall Survival [ Time Frame: 24 Months ]
  4. Safety [ Time Frame: 12 Months ]
    Incidence of adverse events and clinically significant changes in safety lab values, including subgroup analyses

  5. Phase 2 Expanded Cohorts [ 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

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.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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. PD as best response to most recent therapy regimen ii. SD as best response to most recent therapy with duration no longer than 6 month from last dose of therapy OR
    • Refractory post-ASCT i. Disease progression or relapsed less than or equal to 12 months of ASCT (must have biopsy proven recurrence in relapsed subjects) ii. If salvage therapy is given post-ASCT, the subject must have had no response to or relapsed after the last line of therapy
  3. Subjects 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 subjects 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. ANC ≥ 1000/uL
  8. ALC >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 ALT/AST <2.5 ULN
    • Total bilirubin <1.5 mg/dl, except in subjects with Gilbert's syndrome
    • Cardiac ejection fraction >50%, no evidence of pericardial effusion as determined by an ECHO, and no clinically significant pleural effusion
    • Baseline oxygen saturation >92% on room air
  11. All subjects 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. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple 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. Subjects 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. Subjects with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of 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

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): NCT02348216

Contact: Medical Information 844-454-KITE

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

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Kite, A Gilead Company Identifier: NCT02348216     History of Changes
Other Study ID Numbers: KTE-C19-101
First Posted: January 28, 2015    Key Record Dates
Last Update Posted: July 24, 2018
Last Verified: July 2018

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