Study Evaluating the Safety and Efficacy of KTE-C19 in Adult Participants With Refractory Aggressive Non-Hodgkin Lymphoma

Conditions

• High Grade B-cell Lymphoma (HGBCL)
• Primary Mediastinal B-cell Lymphoma (PMBCL)
• Refractory Diffuse Large B Cell Lymphoma (DLBCL)
• Relapsed Diffuse Large B-Cell Lymphoma
• Transformed Follicular Lymphoma (TFL)

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Axicabtagene Ciloleucel — BIOLOGICAL
  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.
• Fludarabine — DRUG
  Administered according to package insert
• Cyclophosphamide — DRUG
  Administered according to package insert
• Levetiracetam — DRUG
  Administered according to package insert
• Tocilizumab — DRUG
  Administered according to package insert
• Dexamethasone — DRUG
  Administered according to package insert
• High-dose methylprednisolone — DRUG
  Administered according to package insert
• Bendamustine — DRUG
  Administered according to package insert
• Rituximab — DRUG
  Administered according to package insert
• Doxorubicin — DRUG
  Administered according to package insert
• Prednisone — DRUG
  Administered according to package insert
• Vincristine — DRUG
  Administered according to package insert
• Ifosfamide — DRUG
  Administered according to package insert
• Carboplatin — DRUG
  Administered according to package insert
• Etoposide — DRUG
  Administered according to package insert
• Gemcitabine — DRUG
  Administered according to package insert
• Oxaliplatin — DRUG
  Administered according to package insert
• Cisplatin — DRUG
  Administered according to package insert
• Methylprednisolone — DRUG
  Administered according to package insert

Study Details

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 Subjects who received an infusion of KTE-C19 will complete the remainder of the 15 year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968.

Key Dates

Start date

Apr 21, 2015

Status verified

May 2024

Primary completion

Jul 27, 2023

Completion

Jul 27, 2023

Study Design

Enrollment

307 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy
  Participants with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL) will receive conditioning chemotherapy (fludarabine 30 mg/m\^2 intravenously \[IV\] over 30 minutes and cyclophosphamide 500 mg/m\^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel chimeric antigen receptor (CAR) transduced autologous T cells administered IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of body weight (BW) on Day 0.
• Experimental: Phase 2 (Pivotal Study): Cohort 1
  Participants with refractory DLBCL will receive conditioning chemotherapy (fludarabine 30 mg/m\^2 IV over 30 minutes and cyclophosphamide 500 mg/m\^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW on Day 0.
• Experimental: Phase 2 (Pivotal Study): Cohort 2
  Participants with refractory PMBCL or TFL will receive conditioning chemotherapy (fludarabine 30 mg/m\^2 IV over 30 minutes and cyclophosphamide 500 mg/m\^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW on Day 0.
• Experimental: Phase 2 (Safety Management Study): Cohort 3
  Participants with relapsed or refractory transplant ineligible DLBCL, PMBCL, or TFL will receive conditioning chemotherapy (fludarabine 30 mg/m\^2 IV over 30 minutes and cyclophosphamide 500 mg/m\^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW on Day 0. Participants will also receive a prophylactic regimen of levetiracetam (750 mg orally or IV twice daily (BID) starting on Day 0) and tocilizumab (8 mg/kg IV over 1 hour (not to exceed 800 mg)) on Day 2).
• Experimental: Phase 2 (Safety Management Study): Cohort 4
  Participants with r/r DLBCL,PMBCL,TFL,or high-grade B-cell lymphoma(HGBCL)after 2 systemic lines of therapy will receive optional bridging therapy(dexamethasone 20mg to 40mg,eitherorally or IV daily for 1 to 4 days or 1g/m\^2 of high-dose methylprednisolone(HDMP)for 3 days with rituximab at 375mg/m\^2 weekly for 3 weeks or bendamustine 90 mg/m\^2 on Days 1 and 2 and rituximab 375mg/m\^2 on Day 1),conditioning chemotherapy(fludarabine 30mg/m\^2 IV and cyclophosphamide 500mg/m\^2 IV)on Days -5,-4, and -3;followed by single infusion of axicabtagene ciloleucel CAR transduced autologous T cells IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW. Participants will receive a prophylactic regimen of levetiracetam(750 mg orally or IV twice daily(BID)starting on Day 0).Participants will receive tocilizumab(initiated on persistent Grade 1 cytokine release syndrome(CRS)for over 24 hours)and dexamethasone(persistent Grade 1 CRS for over 72 hours and at onset of Grade 1 neurologic toxicity).
• Experimental: Phase 2 (Safety Management Study): Cohort 5
  Participants with r/r DLBCL, PMBCL ,TFL, or HGBCL after 2 systemic lines of therapy will receive debulking therapy (R-CHOP:rituximab 375mg/m\^2 D1,doxorubicin 50mg/m\^2 D1,prednisone 100mg D1 to D5,cyclophosphamide 750mg/m\^2 D1,vincristine 1.4 mg/m\^2 D1 or R-ICE:rituximab 375mg/ m\^2 D1,ifosfamide 5g/m\^2 24h-CI D2,carboplatin AUC5 D2 maximum dose 800mg,etoposide 100 mg/m\^2/day D1 to D3 or R-GEMOX:rituximab 375mg/m\^2 D1,gemcitabine 1000mg/m\^2 D2,oxaliplatin 100mg/m\^2 D2 or R-GDP:rituximab 375mg/m\^2 D1 or D8,gemcitabine 1g/m\^2 D1 \& D8,dexamethasone 40mg D1 to D4,cisplatin 75mg/m\^2 D1(or carboplatin AUC5 D1) or radiotherapy:20 to 30 Gy), conditioning chemotherapy (fludarabine 30mg/m\^2 IV and cyclophosphamide 500mg/m\^2 IV)on Days -5,-4, and -3; followed by single infusion of axicabtagene ciloleucel at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW on Day 0. Participants will also receive a prophylactic regimen of levetiracetam (750 mg orally or IV BID starting on D0).D=Day.
• Experimental: Phase 2 (Safety Management Study): Cohort 6
  Participants with r/r DLBCL,PMBCL,TFL orHGBCL after 2 systemic lines of therapy may receive bridging therapy(dexamethasone 20mg to 40mg,orally or IV daily for 1 to 4 days or 1g/m\^2 HDMP for 3 days with rituximab at 375mg/m\^2 weekly for 3 weeks or bendamustine 90 mg/m\^2 on Days 1 and 2 and rituximab 375mg/m\^2 on Day 1),conditioning chemotherapy(fludarabine 30mg/m\^2 IV and cyclophosphamide 500mg/m\^2 IV)on Days -5,-4, and -3; followed by single infusion of axicabtagene ciloleucel CAR transduced autologous T cells IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW on Day 0.Participants will also receive a prophylactic regimen of levetiracetam 750 mg orally or IV twice daily(BID)starting on Day 0)and corticosteroids(dexamethasone, 10 mg once daily on Days 0, 1, and 2).Participants will receive tocilizumab(initiated on persistent Grade 1 CRS for over 24 hours)and dexamethasone(persistent Grade 1 CRS for over 72 hours and at onset of Grade 1 neurologic toxicity).

Primary Outcome Measure

Phase 1 Study: Number of Participants Experiencing Adverse Events (AEs) Defined as Dose Limiting Toxicities (DLTs) [ Time Frame: First infusion date of axicabtagene ciloleucel up to 30 days ]

Locations (23)

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