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Ultra-Low Dose Interleukin-2 for Refractory Chronic Graft Versus Host Disease

22 juni 2020 bijgewerkt door: John Koreth, MD, Dana-Farber Cancer Institute

A Phase I Study of Ultra-Low Dose Subcutaneous Interleukin-2 (IL-2) for Treatment of Refractory Chronic Graft Versus Host Disease

The purpose of this research study is to determine the safety of IL-2 and the highest dose of this drug that can be given safely to people with chronic graft versus host disease (GVHD). Chronic GVHD is a medical condition that may occur after patients receive a bone marrow, stem cell or cord blood transplant. The donor's immune system may recognize their body (the host) as foreign and attempt to "reject" it. Traditional standard therapy to treat chronic GVHD is prednisone (steroids). Treatment options are limited, and it is thought that IL-2 may help to control chronic GVHD.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

  • IL-2 will be given daily through an injection under the skin for a period of 8 weeks. To determine the highest safest dose of IL-2, the dose participants receive will increase as lower doses are determined to be safe. There will be three dose levels.
  • Participants will be seen periodically while they are receiving IL-2. Physical exams and blood tests will be performed weekly for the first two weeks and then every other week until week 8.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

29

Fase

  • Fase 1

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, 02115
        • 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 en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  • Recipients of allogeneic stem cell transplantation with myeloablative or non-myeloablative conditioning regimens
  • Patients must be at least 180 days from the allogeneic stem cell transplantation procedure
  • Steroid refractory cGVHD, defined as having persistent symptoms and signs of GVHD despite the use of prednisone for at least 4 weeks in the preceding 12 months without complete resolution of signs and symptoms.
  • Stable dose of corticosteroids for 4 weeks prior to enrollment
  • No addition or subtraction of other immunosuppressive medications for 4 weeks prior to enrollment.
  • Adequate bone marrow, renal and hepatic function as outlined in the protocol
  • 18 years of age or older
  • ECOG Performance Status of 0-2

Exclusion Criteria:

  • Ongoing prednisone requirement > 1mg/kg/day (or equivalent)
  • Exposure to any new immunosuppressive medication in the 4 weeks prior to enrollment
  • Concurrent ECP therapy within 4 weeks prior to enrollment
  • Post-transplant exposure to any novel immunosuppressive medication within 100 days prior to enrollment
  • Donor lymphocyte infusion within 100 days prior to IL-2 therapy
  • Active malignant disease relapse
  • Active, uncontrolled infection
  • Positive serologic test for Hepatitis B or a positive serologic or nucleic acid test for Hepatitis C
  • HIV seropositivity
  • Life expectancy < 3 months
  • Pregnancy or lactation
  • Inability to comply with IL-2 treatment regimen
  • Uncontrolled cardiac angina or symptomatic congestive heart failure
  • Organ transplant (allograft) recipient

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: Interleukin-2

Interleukin-2 (IL-2) will be given daily through an injection under the skin for a period of 8 weeks. To determine the highest safest dose of IL-2, the dose participants receive will increase as lower doses are determined to be safe. There will be three dose levels:

Dose Level -A 0.3 x 106 (IU/m2/d) Dose Level -B 1 x 106 (IU/m2/d) Dose Level-C 3 x 106 (IU/m2/d)
Geneesmiddel: Interleukin-2
Dose will vary depending upon when participant enters the trial: Given as a daily injection under the skin for 8 weeks.
Andere namen:
  • IL-2

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
The Maximum Tolerated Dose and Toxicity Profile of an 8 Week Course of IL-2 in Patients With cGVHD and an Inadequate Response to Steroids.
Tijdsspanne: Participants were assessed for toxicities at mandatory study follow-up visits during the 8 week course of study therapy and four weeks post therapy

Three dose levels were evaluated to determine the maximally tolerated dose (MTD):

Dose level A: 0.3 x 10^6 IU/m^2/day Dose level B: 1.0 x 10^6 IU/m^2/day Dose level C: 3.0 x 10^6 IU/m^2/day Once the MTD (dose level B) was established, an additional 10 participants were enrolled at this dose.
Participants were assessed for toxicities at mandatory study follow-up visits during the 8 week course of study therapy and four weeks post therapy

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
The Number of Participants Who Tolerated at Least 6 Weeks of Subcutaneous Low Dose IL-2.
Tijdsspanne: Participants were assessed for toxicities at mandatory study follow-up visits during the 8 week course of study therapy and four weeks post therapy. cGVHD was assessed at Weeks 8 and 12

Feasibility: the number of participants who tolerated at least 6 weeks of therapy, and were thus evaluable for response. Efficacy: chronic GVHD response per NIH consensus criteria in evaluable patients.

A complete response was defined as resolution of all reversible chronic GVHD-associated manifestations, a partial response as an improvement of 50% or more on the organ-specific chronic GVHD scale without progression at other organs or sites, progressive disease as an increase of 25% or more on the organ specific chronic GVHD scale, and stable disease as an improvement of less than 50% or increase of less than 25%. Please refer to the Supplementary Appendix in our published report (Koreth et al, NEJM 2011) for further details.
Participants were assessed for toxicities at mandatory study follow-up visits during the 8 week course of study therapy and four weeks post therapy. cGVHD was assessed at Weeks 8 and 12
CD3+T, CD4+T (Including Regulatory CD4+T Cells (Treg) and Conventional CD4+T Cells (Tcon)), CD8+T, NK, NKT and B Cell Counts.
Tijdsspanne: Immunological samples taken at study appointments during the 12 week protocol schedule

Changes in the above immune cell populations (CD3+T, CD4+T (including CD4+Treg and CD4+Tcon), CD8+T, NK, NKT and B cell counts were measured at study appointments during the 8-week IL-2 treatment and four weeks post study therapy.

All study participants (n=28) with a sample available were reported in the data table.

Immune outcome data cannot be meaningfully rendered in the template provided, owing to complexity. The tables below only represent a general overview of the data. Please refer to figure 2 in our published report (Koreth et al, NEJM 2011).
Immunological samples taken at study appointments during the 12 week protocol schedule
Treg Cell:Tcon Cell Ratio
Tijdsspanne: Immunological samples taken at study appointments during the 12 week protocol schedule

Changes in the ratio of the CD4+ regulatory T cell (Treg) and CD4+ conventional T cell (Tcon) counts were measured at study appointments during the 8-week IL-2 treatment and four weeks post study therapy.

All study participants (n=28) with a sample available were reported in the data table.

Immune outcome data cannot be meaningfully rendered in the template provided, owing to complexity. The tables below only represent a general overview of the data. Please refer to figure 2 in our published report (Koreth et al, NEJM 2011).
Immunological samples taken at study appointments during the 12 week protocol schedule

Medewerkers en onderzoekers

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

Sponsor

Dana-Farber Cancer Institute

Medewerkers

Novartis
Brigham and Women's Hospital

Onderzoekers

  • Hoofdonderzoeker: John Koreth, MBBS, D.Phil, Dana-Farber Cancer Institute

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

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

1 augustus 2007

Primaire voltooiing (Werkelijk)

1 juni 2011

Studie voltooiing (Werkelijk)

27 mei 2020

Studieregistratiedata

Eerst ingediend

11 september 2007

Eerst ingediend dat voldeed aan de QC-criteria

11 september 2007

Eerst geplaatst (Schatting)

14 september 2007

Updates van studierecords

Laatste update geplaatst (Werkelijk)

1 juli 2020

Laatste update ingediend die voldeed aan QC-criteria

22 juni 2020

Laatst geverifieerd

1 juni 2020

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 07-083

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