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A Study of Ultra-fraction Radiotherapy Bridging CART in R/R DLBCL

Primary Purpose

Diffuse Large B Cell Lymphoma, CAR-T, Radiotherapy

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
ultra-fraction radiotherapy
Sponsored by
Peking Union Medical College Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B Cell Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Over than 18 years old
  2. Histologically confirmed DLBCL(by central pathology review before enrolment)
  3. Relapsed or refractory disease after ≥2 lines of chemotherapy including rituximab and anthracycline and either having failed autologous Hematopoietic stem cell transplantation (ASCT), or being ineligible for or not consenting to ASCT
  4. Measurable disease at time of enrollment (the maximum diameter of cross section ≥1.5cm)
  5. Life expectancy ≥12 weeks
  6. Able to receive radiotherapy evaluated by specialist

Exclusion Criteria:

  1. Prior radiation therapy within 1 year of infusion
  2. Pregnant or nursing (lactating) women
  3. Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
  4. Previous solid tumor within 3 years, previous or concurrent hematological malignancy
  5. Severe organ dysfunction: left ventricle ejection fraction (LVEF) <40%; DLCO <40%; estimated glomerular filtration rate (eGFR)<30mL/min/1.73 m2; total bilirubin >3 ULN
  6. HIV positive patients, active replication of or prior infection with hepatitis B or active hepatitis C( HCV RNA positive );
  7. Other conditions that the investigator may exclude due to risks or other possibilities

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    treatment group

    Arm Description

    ultra-fraction radiotherapy + CAR-T

    Outcomes

    Primary Outcome Measures

    3-month ORR
    the overall response rate at 3 months after CAR-T cell infusion

    Secondary Outcome Measures

    2-year PFS
    the 2-year progression free survival time from CAR-T cell infusion
    2-year OS
    the 2-year overall survival time from CAR-T cell infusion
    6-month ORR
    the overall response rate at 6 months after CAR-T cell infusion
    DOR
    the duration of response time
    relapse rate
    the cumulative rate of relapse
    the rate of severe side effects
    the rate of severe side effects (CTCAE≥ grade 3）

    Full Information

    First Posted
    August 22, 2022
    Last Updated
    August 22, 2022
    Sponsor
    Peking Union Medical College Hospital
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05514327
    Brief Title
    A Study of Ultra-fraction Radiotherapy Bridging CART in R/R DLBCL
    Official Title
    the Safety and Efficacy of Ultra-fraction Radiotherapy Bridging CART Cell Therapy in Relapsed/Refractory Diffuse Large b Cell Lymphoma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 1, 2022 (Anticipated)
    Primary Completion Date
    September 1, 2024 (Anticipated)
    Study Completion Date
    December 1, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Peking Union Medical College Hospital

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    Brief Summary
    This is a single-arm single center study to prospectively evaluate the safety and efficacy of ultra-fraction radiotherapy bridging CAR-T therapy in relapsed/refractory diffuse large b cell lymphoma

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Diffuse Large B Cell Lymphoma, CAR-T, Radiotherapy, Bridging Therapy

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    20 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    treatment group
    Arm Type
    Experimental
    Arm Description
    ultra-fraction radiotherapy + CAR-T
    Intervention Type
    Radiation
    Intervention Name(s)
    ultra-fraction radiotherapy
    Intervention Description
    the R/R DLBCL patients would receive ultra-fraction radiotherapy as bridging therapy before the CD19 CART cell infusion
    Primary Outcome Measure Information:
    Title
    3-month ORR
    Description
    the overall response rate at 3 months after CAR-T cell infusion
    Time Frame
    3 months
    Secondary Outcome Measure Information:
    Title
    2-year PFS
    Description
    the 2-year progression free survival time from CAR-T cell infusion
    Time Frame
    2 years
    Title
    2-year OS
    Description
    the 2-year overall survival time from CAR-T cell infusion
    Time Frame
    2 years
    Title
    6-month ORR
    Description
    the overall response rate at 6 months after CAR-T cell infusion
    Time Frame
    6 months
    Title
    DOR
    Description
    the duration of response time
    Time Frame
    2 years
    Title
    relapse rate
    Description
    the cumulative rate of relapse
    Time Frame
    2 years
    Title
    the rate of severe side effects
    Description
    the rate of severe side effects (CTCAE≥ grade 3）
    Time Frame
    2 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Over than 18 years old Histologically confirmed DLBCL(by central pathology review before enrolment) Relapsed or refractory disease after ≥2 lines of chemotherapy including rituximab and anthracycline and either having failed autologous Hematopoietic stem cell transplantation (ASCT), or being ineligible for or not consenting to ASCT Measurable disease at time of enrollment (the maximum diameter of cross section ≥1.5cm) Life expectancy ≥12 weeks Able to receive radiotherapy evaluated by specialist Exclusion Criteria: Prior radiation therapy within 1 year of infusion Pregnant or nursing (lactating) women Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion) Previous solid tumor within 3 years, previous or concurrent hematological malignancy Severe organ dysfunction: left ventricle ejection fraction (LVEF) <40%; DLCO <40%; estimated glomerular filtration rate (eGFR)<30mL/min/1.73 m2; total bilirubin >3 ULN HIV positive patients, active replication of or prior infection with hepatitis B or active hepatitis C( HCV RNA positive ); Other conditions that the investigator may exclude due to risks or other possibilities
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Jing Ruan, Docter
    Phone
    +8615201435860
    Email
    ruanjing@pumch.cn

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    the study protocol, statistical analysis plan, informed consent form, clinical study report would be available upon email request in 3 years after the closure of the study
    IPD Sharing Time Frame
    3 years after the closure of the study
    IPD Sharing Access Criteria
    upon email request
    Citations:
    PubMed Identifier
    31364596
    Citation
    Minn I, Rowe SP, Pomper MG. Enhancing CAR T-cell therapy through cellular imaging and radiotherapy. Lancet Oncol. 2019 Aug;20(8):e443-e451. doi: 10.1016/S1470-2045(19)30461-9. Epub 2019 Jul 29.
    Results Reference
    background
    PubMed Identifier
    35485402
    Citation
    Kuhnl A, Roddie C, Kirkwood AA, Tholouli E, Menne T, Patel A, Besley C, Chaganti S, Sanderson R, O'Reilly M, Norman J, Osborne W, Bloor A, Lugthart S, Malladi R, Patten PEM, Neill L, Martinez-Cibrian N, Kennedy H, Phillips EH, Jones C, Sharplin K, El-Sharkawi D, Latif AL, Mathew A, Uttenthal B, Stewart O, Marzolini MAV, Townsend W, Cwynarski K, Ardeshna K, Ardavan A, Robinson K, Pagliuca A, Collins GP, Johnson R, McMillan A. A national service for delivering CD19 CAR-Tin large B-cell lymphoma - The UK real-world experience. Br J Haematol. 2022 Aug;198(3):492-502. doi: 10.1111/bjh.18209. Epub 2022 Apr 29.
    Results Reference
    background
    PubMed Identifier
    31219975
    Citation
    Qu C, Ping N, Kang L, Liu H, Qin S, Wu Q, Chen X, Zhou M, Xia F, Ye A, Kong D, Li C, Yu L, Wu D, Jin Z. Radiation Priming Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma With High Tumor Burden. J Immunother. 2020 Jan;43(1):32-37. doi: 10.1097/CJI.0000000000000284.
    Results Reference
    background
    PubMed Identifier
    31175906
    Citation
    Sim AJ, Jain MD, Figura NB, Chavez JC, Shah BD, Khimani F, Lazaryan A, Krivenko G, Davila ML, Liu HD, Falchook AD, Dahiya S, Rapoport AP, Kim S, Locke FL, Robinson TJ. Radiation Therapy as a Bridging Strategy for CAR T Cell Therapy With Axicabtagene Ciloleucel in Diffuse Large B-Cell Lymphoma. Int J Radiat Oncol Biol Phys. 2019 Dec 1;105(5):1012-1021. doi: 10.1016/j.ijrobp.2019.05.065. Epub 2019 Jun 5.
    Results Reference
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    PubMed Identifier
    34526365
    Citation
    Manjunath SH, Cohen AD, Lacey SF, Davis MM, Garfall AL, Melenhorst JJ, Maxwell R, Arscott WT, Maity A, Jones JA, Plastaras JP, Stadtmauer EA, Levine BL, June CH, Milone MC, Paydar I. The Safety of Bridging Radiation with Anti-BCMA CAR T-Cell Therapy for Multiple Myeloma. Clin Cancer Res. 2021 Dec 1;27(23):6580-6590. doi: 10.1158/1078-0432.CCR-21-0308. Epub 2021 Sep 15.
    Results Reference
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    PubMed Identifier
    30415658
    Citation
    DeSelm C, Palomba ML, Yahalom J, Hamieh M, Eyquem J, Rajasekhar VK, Sadelain M. Low-Dose Radiation Conditioning Enables CAR T Cells to Mitigate Antigen Escape. Mol Ther. 2018 Nov 7;26(11):2542-2552. doi: 10.1016/j.ymthe.2018.09.008. Epub 2018 Sep 13.
    Results Reference
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    A Study of Ultra-fraction Radiotherapy Bridging CART in R/R DLBCL

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