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NCT02348216 · OUTCOME

Pharmacodynamics: Peak Level of Cytokines (Ferritin, ICAM-1, IL-2 R, Perforin, and VCAM-1) in Serum (Phase 2 Cohorts 4, 5, and 6)

Study Evaluating the Safety and Efficacy of KTE-C19 in Adult Participants With Refractory Aggressive Non-Hodgkin Lymphoma · Source last updated 2024-06-04

Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.

Measure
MEDIAN
Unit
ng/mL
Interval / dispersion
Full Range
Time frame
Baseline up to Month 3

What was measured

Peak was defined as the maximum post-baseline level of the cytokine. Following key cytokines were measured: Ferritin, ICAM-1, IL-2 R, Perforin, and VCAM-1.

Analysis population: Participants in the Safety Analysis Set were analyzed.

Groups in this outcome

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 received optional bridging therapy (dexamethasone 20mg to 40mg,either orally 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 also received a prophylactic regimen of levetiracetam (750 mg orally or IV twice daily (BID) starting on Day 0). Participants received 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).

Phase 2 (Safety Management Study): Cohort 5

Participants with r/r DLBCL, PMBCL ,TFL, or HGBCL after 2 systemic lines of therapy received 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 also received a prophylactic regimen of levetiracetam (750 mg orally or IV BID starting on D0).D=Day.

Phase 2 (Safety Management Study): Cohort 6

Participants with r/r DLBCL, PMBCL ,TFL, or HGBCL after 2 systemic lines of therapy may have received bridging therapy (dexamethasone 20mg to 40mg, either orally 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 on Day 0. Participants also received 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 received 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).

Group identifiers and denominators belong to this outcome only. They may differ in another outcome or in safety reporting.

Analysis denominator · Participants

GroupSource count
Phase 2 (Safety Management Study): Cohort 441
Phase 2 (Safety Management Study): Cohort 550
Phase 2 (Safety Management Study): Cohort 640

Reported measurements

Ferritin
Values in ng/mL · Interval/dispersion: Full Range
GroupValueSpreadLowerUpperComment
Phase 2 (Safety Management Study): Cohort 41086.36Not reported95.5523900Not reported
Phase 2 (Safety Management Study): Cohort 51516.11Not reported89.2931600Not reported
Phase 2 (Safety Management Study): Cohort 6903.50Not reported171.616555.10Not reported
ICAM-1
Values in ng/mL · Interval/dispersion: Full Range
GroupValueSpreadLowerUpperComment
Phase 2 (Safety Management Study): Cohort 4907.97Not reported359.515141.64Not reported
Phase 2 (Safety Management Study): Cohort 5636.74Not reported361.384835.93Not reported
Phase 2 (Safety Management Study): Cohort 6654.81Not reported355.154419.09Not reported
IL-2 R
Values in ng/mL · Interval/dispersion: Full Range
GroupValueSpreadLowerUpperComment
Phase 2 (Safety Management Study): Cohort 410.78Not reported2.8194.59Not reported
Phase 2 (Safety Management Study): Cohort 57.82Not reported1.3683.60Not reported
Phase 2 (Safety Management Study): Cohort 66.43Not reported1.7033.31Not reported
Perforin
Values in ng/mL · Interval/dispersion: Full Range
GroupValueSpreadLowerUpperComment
Phase 2 (Safety Management Study): Cohort 417.22Not reported3.8844.42Not reported
Phase 2 (Safety Management Study): Cohort 510.85Not reported2.53100.00Not reported
Phase 2 (Safety Management Study): Cohort 610.12Not reported1.9739.62Not reported
VCAM-1
Values in ng/mL · Interval/dispersion: Full Range
GroupValueSpreadLowerUpperComment
Phase 2 (Safety Management Study): Cohort 41255.32Not reported594.513932.61Not reported
Phase 2 (Safety Management Study): Cohort 5854.63Not reported476.606501.14Not reported
Phase 2 (Safety Management Study): Cohort 6836.04Not reported411.935079.25Not reported
Complete source fields
classes
  1. categories
    1. measurements
      1. group Id
        OG000
        lower Limit
        95.55
        upper Limit
        23900
        value
        1086.36
      2. group Id
        OG001
        lower Limit
        89.29
        upper Limit
        31600
        value
        1516.11
      3. group Id
        OG002
        lower Limit
        171.61
        upper Limit
        6555.10
        value
        903.50
    title
    Ferritin
  2. categories
    1. measurements
      1. group Id
        OG000
        lower Limit
        359.51
        upper Limit
        5141.64
        value
        907.97
      2. group Id
        OG001
        lower Limit
        361.38
        upper Limit
        4835.93
        value
        636.74
      3. group Id
        OG002
        lower Limit
        355.15
        upper Limit
        4419.09
        value
        654.81
    title
    ICAM-1
  3. categories
    1. measurements
      1. group Id
        OG000
        lower Limit
        2.81
        upper Limit
        94.59
        value
        10.78
      2. group Id
        OG001
        lower Limit
        1.36
        upper Limit
        83.60
        value
        7.82
      3. group Id
        OG002
        lower Limit
        1.70
        upper Limit
        33.31
        value
        6.43
    title
    IL-2 R
  4. categories
    1. measurements
      1. group Id
        OG000
        lower Limit
        3.88
        upper Limit
        44.42
        value
        17.22
      2. group Id
        OG001
        lower Limit
        2.53
        upper Limit
        100.00
        value
        10.85
      3. group Id
        OG002
        lower Limit
        1.97
        upper Limit
        39.62
        value
        10.12
    title
    Perforin
  5. categories
    1. measurements
      1. group Id
        OG000
        lower Limit
        594.51
        upper Limit
        3932.61
        value
        1255.32
      2. group Id
        OG001
        lower Limit
        476.60
        upper Limit
        6501.14
        value
        854.63
      3. group Id
        OG002
        lower Limit
        411.93
        upper Limit
        5079.25
        value
        836.04
    title
    VCAM-1
denoms
  1. counts
    1. group Id
      OG000
      value
      41
    2. group Id
      OG001
      value
      50
    3. group Id
      OG002
      value
      40
    units
    Participants
description
Peak was defined as the maximum post-baseline level of the cytokine. Following key cytokines were measured: Ferritin, ICAM-1, IL-2 R, Perforin, and VCAM-1.
dispersion Type
Full Range
groups
  1. description
    Participants with r/r DLBCL, PMBCL ,TFL, or high-grade B-cell lymphoma (HGBCL) after 2 systemic lines of therapy received optional bridging therapy (dexamethasone 20mg to 40mg,either orally 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 also received a prophylactic regimen of levetiracetam (750 mg orally or IV twice daily (BID) starting on Day 0). Participants received 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).
    id
    OG000
    title
    Phase 2 (Safety Management Study): Cohort 4
  2. description
    Participants with r/r DLBCL, PMBCL ,TFL, or HGBCL after 2 systemic lines of therapy received 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 also received a prophylactic regimen of levetiracetam (750 mg orally or IV BID starting on D0).D=Day.
    id
    OG001
    title
    Phase 2 (Safety Management Study): Cohort 5
  3. description
    Participants with r/r DLBCL, PMBCL ,TFL, or HGBCL after 2 systemic lines of therapy may have received bridging therapy (dexamethasone 20mg to 40mg, either orally 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 on Day 0. Participants also received 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 received 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).
    id
    OG002
    title
    Phase 2 (Safety Management Study): Cohort 6
param Type
MEDIAN
population Description
Participants in the Safety Analysis Set were analyzed.
reporting Status
POSTED
time Frame
Baseline up to Month 3
title
Pharmacodynamics: Peak Level of Cytokines (Ferritin, ICAM-1, IL-2 R, Perforin, and VCAM-1) in Serum (Phase 2 Cohorts 4, 5, and 6)
type
SECONDARY
unit Of Measure
ng/mL

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