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A Phase I Trial of Donor- Derived 19-28z CAR T Cells Following Allogeneic Transplant for the Treatment of CD19 Malignancies

4. marts 2022 opdateret af: Memorial Sloan Kettering Cancer Center

A Phase I Trial Evaluating the Safety of Consolidative Infusions of CD19-Specific Chimeric Antigen Receptor (CAR) T Cells Following T-cell Depleted Allogeneic Transplantation for High Risk B-cell Malignancies

The purposed of this study is to determine whether an infusion with specialized 'modified T cells' (or CD19 chimeric antigen T cells, also called CD19 CAR T cells) that target the B cell marker will reduce the risk of relapse after transplant.

Studieoversigt

Status

Trukket tilbage

Intervention / Behandling

Undersøgelsestype

Interventionel

Fase

  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

    • New York
      • New York, New York, Forenede Stater, 10065
        • Memorial Sloan Kettering Cancer Center

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 60 år (Voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

The following criteria must be met prior to the allogenic transplantation:

  1. ALL in second remission or greater (≥ CR2)

    • Please refer to section 3.0 for more discussion of ALL in CR1 versus CR2
  2. CLL

    1. High risk in any remission status as defined by 17p deletion or Richter's transformation, or
    2. All other patients eligible after at least 2 lines of standard or investigational chemotherapy
  3. B-NHL

    1. Refractory or stable disease to last line of therapy per ICML 2014. Patients should have at least 2 lines of prior therapy.
    2. Relapsed disease in patients who are not candidates for autologous transplant
  4. Patient's age is ≥ 18 and ≤ 60.
  5. KPS ≥ 70%
  6. Patients must have CD19 expression (by any detection method) demonstrated on their malignant cells at the time of enrollment on the protocol.
  7. Patients relapsed after prior CD19 CAR T cell or blinatumomab are eligible for enrollment as long as CD19 expression is still prese on the malignant cells.
  8. Patients who have a matched related donor willing to donate HSC for allograft and PBMC for CAR T cell generation
  9. Patients must have adequate organ function measured by:

    1. Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > 50%
    2. Hepatic: < 3x ULN ALT and < 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia.
    3. Renal: serum creatinine <1.3 mg/dl or if serum creatinine is outside the normal range, then CrCl > 60 ml/min (measured or calculated/estimated)
    4. Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for hemoglobin)
    5. Negative serum pregnancy test for women of child-bearing potential is required

Exclusion Criteria:

  1. Active and uncontrolled infection at time of transplantation. Please note that patients being actively treated for a viral reactivation may be enrolled on the protocol at the discretion of the investigators.
  2. Patients who have undergone a prior allogeneic or autologous stem cell transplant within the previous six months.
  3. Pregnant or breast feeding
  4. HIV infection
  5. Progressive disease at time of transplant
  6. Patients with known autoimmune disease.
  7. Patients with active or clinically significant neurological disorders, such as seizure disorders.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomiseret
  • Interventionel model: Sekventiel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Cohort -1

Cohorts of 3-6 patients each will be treated with escalating doses of consolidative modified T cells at Day 30 (+/- 5 days) post allo-HSCT

Total T-Cell Dose: 1 x 10^4 cells/kg

Dose Level -1: 1 x 10^4 cells/kg Dose Level 1: 1 x 10^5 cells/kg Dose Level 2: 2 x 10^5 cells/kg Dose Level 3: 4 x 10^5 cells/kg
Eksperimentel: Cohort 1

Cohorts of 3-6 patients each will be treated with escalating doses of consolidative modified T cells at Day 30 (+/- 5 days) post allo-HSCT

Total T-Cell Dose: 1 x 10^5 cells/kg

Dose Level -1: 1 x 10^4 cells/kg Dose Level 1: 1 x 10^5 cells/kg Dose Level 2: 2 x 10^5 cells/kg Dose Level 3: 4 x 10^5 cells/kg
Eksperimentel: Cohort II

Cohorts of 3-6 patients each will be treated with escalating doses of consolidative modified T cells at Day 30 (+/- 5 days) post allo-HSCT

Total T-Cell Dose: 2 x 10^5 cells/kg

Dose Level -1: 1 x 10^4 cells/kg Dose Level 1: 1 x 10^5 cells/kg Dose Level 2: 2 x 10^5 cells/kg Dose Level 3: 4 x 10^5 cells/kg
Eksperimentel: Cohort III

Cohorts of 3-6 patients each will be treated with escalating doses of consolidative modified T cells at Day 30 (+/- 5 days) post allo-HSCT

Total T-Cell Dose: 4 x 10^5 cells/kg

Dose Level -1: 1 x 10^4 cells/kg Dose Level 1: 1 x 10^5 cells/kg Dose Level 2: 2 x 10^5 cells/kg Dose Level 3: 4 x 10^5 cells/kg

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Maximum tolerated dose (MTD)
Tidsramme: 24 month
To determine maximum tolerated dose (MTD) of intravenously administered allogeneic, donor-derived 19-28z CAR T cells administered following TCD allo-HSCT for patients with high-risk CD19+ malignancies
24 month

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Efterforskere

  • Ledende efterforsker: Miguel-Angel Perales, MD, Memorial Sloan Kettering Cancer Center

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

1. juli 2021

Primær færdiggørelse (Faktiske)

1. marts 2022

Studieafslutning (Faktiske)

1. marts 2022

Datoer for studieregistrering

Først indsendt

15. september 2020

Først indsendt, der opfyldte QC-kriterier

15. september 2020

Først opslået (Faktiske)

21. september 2020

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

18. marts 2022

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

4. marts 2022

Sidst verificeret

1. marts 2022

Mere information

Begreber relateret til denne undersøgelse

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

JA

IPD-planbeskrivelse

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

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Kliniske forsøg med CAR T-Cell Infusion

3
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