Clinical Trials /

A Phase 2 Multicenter Study of Axicabtagene Ciloleucel in Subjects With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma

NCT03105336

Description:

This study will enroll approximately 160 adult subjects who have relapsed or refractory (r/r) iNHL to be infused with the study treatment, axicabtagene ciloleucel, to see if their disease responds to this experimental product and if this product is safe. Axicabtagene ciloleucel is made from the subjects own white blood cells which are genetically modified and grown to fight cancer. An objective response rate of 70% is targeted.

Related Conditions:
  • Follicular Lymphoma
  • Marginal Zone Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase 2 Multicenter Study of Axicabtagene Ciloleucel in Subjects With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma
  • Official Title: A Phase 2 Multicenter Study of Axicabtagene Ciloleucel in Subjects With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (iNHL)

Clinical Trial IDs

  • ORG STUDY ID: KTE-C19-105
  • SECONDARY ID: 2017-001912-13
  • NCT ID: NCT03105336

Conditions

  • Follicular Lymphoma
  • Marginal Zone Lymphoma
  • Indolent Non-Hodgkin Lymphoma

Interventions

DrugSynonymsArms
axicabtagene ciloleucelYescarta®axicabtagene ciloleucel
Cyclophosphamideaxicabtagene ciloleucel
Fludarabineaxicabtagene ciloleucel

Purpose

This study will enroll approximately 160 adult subjects who have relapsed or refractory (r/r) iNHL to be infused with the study treatment, axicabtagene ciloleucel, to see if their disease responds to this experimental product and if this product is safe. Axicabtagene ciloleucel is made from the subjects own white blood cells which are genetically modified and grown to fight cancer. An objective response rate of 70% is targeted.

Detailed Description

      This study will enroll approximately 160 adult subjects who have relapsed or refractory (r/r)
      iNHL to be infused with the study treatment, axicabtagene ciloleucel, to see if their disease
      responds to this experimental product and if this product is safe. Axicabtagene ciloleucel is
      made from the subjects own white blood cells which are genetically modified and grown to
      fight cancer. An objective response rate of 70% is targeted.

      All enrolled subjects will be screened for eligibility then will undergo leukapheresis to
      collect white blood cells for manufacturing. In preparation for the infusion with
      axicabtagene ciloleucel, subjects will undergo conditioning chemotherapy with
      cyclophosphamide and fludarabine for 3 days to help the study treatment be effective. After
      the product is manufactured and conditioning chemotherapy period is complete, subjects will
      be infused with axicabtagene ciloleucel and then monitored in a hospital for a minimum of 7
      days. Subjects will be followed by their study doctor for continued monitoring of the safety
      and effectiveness of the study treatment for approximately 3 months after receiving treatment
      and then will be followed for safety for up to an additional 15 years.
    

Trial Arms

NameTypeDescriptionInterventions
axicabtagene ciloleucelExperimental
  • axicabtagene ciloleucel
  • Cyclophosphamide
  • Fludarabine

Eligibility Criteria

        Key Inclusion Criteria:

          1. Individual has [follicular lymphoma or marginal zone lymphoma that has progressed
             after at least 2 lines of treatment with combination chemoimmunotherapy] (e.g.
             R-bendamustine, R-CHOP).

          2. Individual has [measurable disease].

          3. Individual has no known presence or history of central nervous system (CNS)
             involvement by lymphoma.

          4. If individual is on conventional systemic therapy or systemic inhibitory/stimulatory
             immune checkpoint therapy, individual is able to stop conventional therapy 2 weeks or
             5 half-lives, whichever is shorter, or immune checkpoint therapy 3 half-lives prior to
             planned leukapheresis.

          5. Individual has Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 and
             adequate renal, hepatic, pulmonary, and cardiac function

          6. Individual is not pregnant or breastfeeding (female individuals only) and is willing
             to use birth control from the time of consent through 6 months following chimeric
             antigen receptor (CAR) T cell infusion (both male and female individuals).

        Key Exclusion Criteria:

          1. Transformed follicular lymphoma (FL) or marginal zone lymphoma (MZL)

          2. Small lymphocytic lymphoma

          3. Histological Grade 3b FL

          4. Individual will have undergone autologous transplant within 6 weeks of planned
             leukapheresis or has undergone allogeneic transplant.

          5. Individual has evidence of involvement of the heart by lymphoma or requirement for
             urgent therapy due to ongoing or impending oncologic emergency (e.g. mass effect,
             tumor lysis syndrome, etc.)

        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:Objective response rate per central read
Time Frame:Up to 15 years
Safety Issue:
Description:Complete response (CR) + partial response (PR) per the Lugano Classiciation (Cheson et al, 2014).

Secondary Outcome Measures

Measure:CR Rate per central read
Time Frame:Up to 15 years
Safety Issue:
Description:CRR is defined as the incidence of CR as best response to treatment by the Lugano Classification (Cheson et al, 2014)
Measure:DOR
Time Frame:Up to 15 years
Safety Issue:
Description:DOR is defined only for subjects who experience an objective response and is the time from the first objective response to disease progression per (Cheson et al, 2014) or disease-related death, whichever comes first.
Measure:PFS
Time Frame:Up to 15 years
Safety Issue:
Description:PFS is defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression per (Cheson et al, 2014) or death from any cause.
Measure:Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:Up to 15 years
Safety Issue:
Description:OS is defined as the time from KTE-C19 infusion to the date of death.
Measure:Levels of anti-CD19 CAR T cells in blood
Time Frame:At enrollment, Day 7, Week 2, Week 4, Month 3, Month 6, Month 12, Month 18, Month 24, annually up to year 5.
Safety Issue:
Description:
Measure:Levels of cytokines in serum
Time Frame:At enrollment, prior to axicabtagene ciloleucel infusion on Day 0, Day 3, Day 7, Week 2, Week 4
Safety Issue:
Description:
Measure:Percentage of Participants experiencing anti-axicabtagene ciloleucel antibodies
Time Frame:At enrollment, Week 4, Month 3, every 3 months up to Month 12
Safety Issue:
Description:
Measure:Percentage of Participants Experiencing clinically significant changes in lab values
Time Frame:Up to 5 years
Safety Issue:
Description:

Details

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

Last Updated

December 10, 2019