Clinical Trials /

Safety and Efficacy of KTE-C19 in Adults With Refractory Aggressive Non-Hodgkin Lymphoma

NCT02348216

Description:

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

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • High Grade B-Cell Lymphoma, Not Otherwise Specified
  • Primary Mediastinal B-Cell Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety and Efficacy of KTE-C19 in Adults With Refractory Aggressive Non-Hodgkin Lymphoma
  • Official Title: A Phase 1/2 Multicenter Study Evaluating the Safety and Efficacy of KTE-C19 in Adults With Refractory Aggressive Non-Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: KTE-C19-101
  • SECONDARY ID: 2015-005007-86
  • NCT ID: NCT02348216

Conditions

  • 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)

Interventions

DrugSynonymsArms
Axicabtagene CiloleucelYescarta®Axicabtagene Ciloleucel
FludarabineAxicabtagene Ciloleucel
CyclophosphamideAxicabtagene Ciloleucel

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Axicabtagene CiloleucelExperimentalA conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, axicabtagene ciloleucel.
  • Axicabtagene Ciloleucel
  • Fludarabine
  • Cyclophosphamide

Eligibility 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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1 Study: Percentage of Participants Experiencing Adverse Events defined as Dose Limiting Toxicities (DLTs)
Time Frame:Up to 30 Days
Safety Issue:
Description:Dose-limiting toxicity is defined as protocol-defined axicabtagene ciloleucel related events with onset within the first 30 days following axicabtagene ciloleucel infusion.

Secondary Outcome Measures

Measure:Duration of Response (DOR)
Time Frame:Up to 12 months
Safety Issue:
Description: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.
Measure:Phase 1 Study: ORR
Time Frame:Up to 12 months
Safety Issue:
Description: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.
Measure:Phase 2 Study: ORR per Independent Radiological Review Committee (IRRC)
Time Frame:Up to 12 months
Safety Issue:
Description:ORR is defined as the incidence of either a complete response (CR) or a partial response (PR) per the IRRC.
Measure:Progression-Free Survival (PFS)
Time Frame:Up to 12 months
Safety Issue:
Description: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.
Measure:Overall Survival (OS)
Time Frame:Up to 24 months
Safety Issue:
Description:OS is defined as the time from axicabtagene ciloleucel infusion to the date of death.
Measure:Percentage of Participants Experiencing Adverse Events
Time Frame:Up to 12 months
Safety Issue:
Description:
Measure:Percentage of Participants Experiencing Clinically Significant Changes in Safety Lab Values
Time Frame:Up to 12 months
Safety Issue:
Description:
Measure:Percentage of Participants with Anti-Axicabtagene Ciloleucel Antibodies
Time Frame:Up to 12 months
Safety Issue:
Description:
Measure:Pharmacokinetics (Levels of Anti-CD19 CAR T Cells in Blood)
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Pharmacodynamics (Levels of Cytokines in Serum)
Time Frame:Up to 12 months
Safety Issue:
Description:
Measure:Phase 2 Safety Management Study: ORR
Time Frame:Up to 12 months
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure:Phase 2 Safety Management Study: Changes Over Time in the Visual Analogue Scale (VAS) Score
Time Frame:Up to 5 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Kite, A Gilead Company

Last Updated

December 19, 2019