Deze pagina is automatisch vertaald en de nauwkeurigheid van de vertaling kan niet worden gegarandeerd. Raadpleeg de Engelse versie voor een brontekst.

Ex Vivo TCR αβ T Cell Depletion for Graft-Versus-Host Disease Prophylaxis in Mismatched Donor Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies

15 april 2022 bijgewerkt door: Vincent T. Ho, MD, Dana-Farber Cancer Institute

A Phase 2 Study of Ex Vivo TCR αβ T Cell Depletion for Graft-Versus-Host Disease (GVHD) Prophylaxis in Mismatched Donor Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies

This research study is studying the removal of a subset of white blood cells (called alpha/beta T cells) from the donor product using a cell separation device before the product is transplanted into the participant.

The device used to remove the α/βT cells in this study is:

-CliniMACS® TCR α/β Reagent System

Studie Overzicht

Toestand

Beëindigd

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

Patients who receive an allogeneic (using another person as the donor) stem cell transplant (SCT) are at risk for developing graft-versus-host disease (GVHD).

The word "graft" refers to the donor blood cells that you will receive during the transplant. The word "host" refers to the person receiving the cells. GVHD is a complication of transplantation where the donor graft attacks and damages some of the participant's tissues.

GVHD may occur when the T cells (a type of white blood cell that helps protect the body from infection) from the donor react against normal tissues or organs in the body. There are two basic types of GVHD:

  • Acute GVHD often occurs early (generally first 3-6 months after SCT) may affect skin, gastrointestinal tract (stomach and intestines) and liver.
  • Chronic GVHD often occurs later (Usually after 3-6 months after SCT) and may affect many organs and significantly diminish quality of life.

To confirm the diagnosis of acute or chronic GVHD, the participant may be asked to have a biopsy (a small sample of the participant's tissue to look at under the microscope) of the skin, gut, or, rarely, the liver.

In this research study, the investigator are investigating a pre-transplant intervention aimed to prevent GVHD by processing the donor product with the Miltenyi CliniMACS TCR α/β Reagent System. The Reagent System will remove certain cells (called T-Cell Receptor (TCR) α/β positive T-cells) that are thought to cause GVHD from donor product before it is given to the participant. By selectively removing this specific type of T cells from the donor product, the investigators hope to reduce the risk for GVHD without reducing the efficacy of the transplant.

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved CliniMACS α/β T cell depletion system for use in the US, but this system is approved by the European Medicines Agency (EMA) and used in Europe

Studietype

Ingrijpend

Inschrijving (Werkelijk)

2

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Verenigde Staten
    • Massachusetts
      • Boston, Massachusetts, Verenigde Staten, 02215
        • Dana Farber Cancer Institute

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 65 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  • Diagnoses and stage at time of transplant admission:

    • Acute leukemia (AML or ALL or MPAL) in first or subsequent remission
    • Myelodysplastic syndromes (MDS) with <10% marrow blasts
    • Myeloproliferative neoplasm (MPN) with <10% marrow blasts
    • CMML with less than 10% marrow blast
    • CML accelerated phase or second or subsequent chronic phase
    • Non-Hodgkin's lymphoma in PR or CR2 or beyond
    • Hodgkin lymphoma in PR or CR2 or beyond
  • Age 18-65 years
  • Patient has a related or unrelated donor who is 8 or 9 out of 10 match at HLA A, B, C, DRB1 and DQB1, based on allele level typing.
  • Patient ECOG performance status 0-2 (Karnofsky ≥60%, see Appendix A)
  • Patient deemed to be appropriate candidate for myeloablative conditioning transplantation.
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patient with active HIV infection
  • Chronic active hepatitis B infection (HepB surface Ag+ or detectable Hep B viral load)
  • Prior allogeneic hematopoietic stem cell transplantation
  • Impaired cardiac function- ejection fraction < 40%
  • Impaired pulmonary function- pretransplant FEV1, DLCO < 50%

  • Impaired renal function, based on

    --Serum creatinine > 2.0 mg/dl

  • Impaired liver function unrelated to primary disease, based on

    --ALT or AST > 3x ULN, or Total Bilirubin > 2.0mg/dl (with exception for known or suspected Gilbert's disease)

  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Women who are pregnant or breast feeding. Women of child bearing potential must have a negative serum pregnancy test at study entry.
  • Participants who are receiving any other investigational agents are eligible but such agent must be discontinued before admission for HSCT, and if resumption of investigation agent is planned after HSCT, this must be approved by the study PI.
  • Participants with known active CNS disease. CNS disease that has been treated is eligible

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: TCR α/β Reagent System
  • The stem cell apheresis product will be depleted of TCRαβ T cells by negative selection using the automated CliniMACS® Plus device.
  • CD34+ stem cell counts will be obtained before and after processing with the Miltenyi ClinicMACs device
Apparaat: ClinicMACs
The Reagent System will remove certain cells (called T-Cell Receptor (TCR) α/β positive T-cells) that are thought to cause GVHD from donor product before it is given to participants

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Number of Participants With Severe Acute GVHD-free Survival
Tijdsspanne: 100 Days
Number of participants with severe acute GVHD-free survival will be assessed at 100 days post-SCT
100 Days

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Number of Participants With Grades II-IV Acute GVHD
Tijdsspanne: 2 years
Grades II-IV acute GVHD will be assessed at 2 years post-SCT. Grade I GVHD is characterized as mild disease, grade II as moderate, grade III as severe, and grade IV as life-threatening. Higher grades of acute GVHD are associated with worse outcomes. Acute GVHD will be staged by assessment of clinical manifestations in the skin, gastrointestinal tract, and liver.
2 years
Number of Participants With Chronic GVHD
Tijdsspanne: 2 years
Number of participants with chronic GVHD will be assessed at 2 years post-SCT.
2 years
Number of Participants With GVHD and Relapse Free Survival (GRFS)
Tijdsspanne: 2 years
GRFS will be defined as alive without having experienced grade III-IV acute GVHD, moderate/severe chronic GVHD, or relapse of underlying malignancy.
2 years
Number of Participants With Immunosuppression-free Survival
Tijdsspanne: 2 years
Number of participants with immunosuppression-free survival will be assessed at 2 years post-SCT.
2 years
Number of Participants With Hematologic Recovery
Tijdsspanne: 2 years
Hematologic recovery will be assessed in participants at 2 years post-SCT.
2 years
Number of Participants With Immune Reconstitution
Tijdsspanne: 2 years
Immune reconstitution will be assessed in participants at 2 years post-SCT.
2 years
Number of Participants With Disease Relapse
Tijdsspanne: 2 years
Disease relapse will be assessed in participants at 2 years post-SCT.
2 years
Number of Participants With Transplant-related Mortality
Tijdsspanne: 2 years
Participant transplant-related mortality will be assessed at 2 years post-SCT.
2 years
Number of Participants With Organ Toxicity
Tijdsspanne: 2 years
Participant organ toxicity will be assessed at 2 years post-SCT.
2 years
Rates of Infections
Tijdsspanne: 2 years
Participant rate of infections will be assessed at 2 years post-SCT.
2 years
Number of Participants With Relapse-free and Overall Survival
Tijdsspanne: 2 years
Number of participants with relapse-free and overall survival will be assessed at 2 years post-SCT.
2 years

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Dana-Farber Cancer Institute

Onderzoekers

  • Hoofdonderzoeker: Vincent T Ho, MD, Dana-Farber Cancer Institute

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

21 januari 2020

Primaire voltooiing (Werkelijk)

26 april 2021

Studie voltooiing (Werkelijk)

26 april 2021

Studieregistratiedata

Eerst ingediend

22 oktober 2018

Eerst ingediend dat voldeed aan de QC-criteria

22 oktober 2018

Eerst geplaatst (Werkelijk)

24 oktober 2018

Updates van studierecords

Laatste update geplaatst (Werkelijk)

10 mei 2022

Laatste update ingediend die voldeed aan QC-criteria

15 april 2022

Laatst geverifieerd

1 april 2022

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 18-270

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Ja

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

Abonneren