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Graft-Versus-Host DiseasePhase 2NCT01428973

Minitransplants With HLA-matched Donors : Comparison Between 2 GVHD Prophylaxis Regimens

A Phase 2 study testing Mycophenolate mofetil and Sirolimus in people with Graft-Versus-Host Disease and Hematological Malignancies, run by University of Liege at 13 sites in Belgium.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The present project is a multicenter phase II trail aiming at comparing which of the two postgrafting immunosuppressive regimens proposed in this study will be best suited to prevent graft-versus-host disease (GVDH). Read more about this study

Who is it for?
Ages 16 to 75 years
What is being tested?
Mycophenolate mofetil and Sirolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
200 participants
Where
13 sitesBelgium
Study dates
Sep 2011to Dec 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Hematological malignancies confirmed histologically and not rapidly progressing:
  • Acute myeloid leukemia (AML) in complete remission (CR) (defined as ≤ 5% marrow blasts and absence of blasts in the peripheral blood);
  • Myelodysplastic syndromes (MDS) with ≤ 5% marrow blasts and absence of blasts in the peripheral blood;
  • Chronic myeloid leukemia (CML) in chronic phase (CP);
  • Myeloproliferative neoplasms not in blast crisis and not with extensive marrow fibrosis;
  • Acute lymphoid leukemia (ALL)in CR;
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  • Multiple myeloma not rapidly progressing;
  • chronic lymphocytic leukemia (CLL);
  • Non-Hodgkin's lymphoma (aggressive NHL should have chemosensitive disease);
  • Hodgkin's disease with chemosensitive disease;
  • 10/10 HLA-A, -B, -C, DRB1 and DQBI allele-matched donor fit to/willing to donate PBSC.
  • Clinical situations:
  • Theoretical indication for a standard allotransplant, but not feasible because:
  • Age > 50 yrs;
  • Unacceptable end organ performance;
  • At the physician's decision;
  • Patient's refusal.
  • Indication for a standard auto-transplant: perform mini-allotransplantation 2-6 months after standard autotransplant.
  • Other inclusion criteria:
  • Male or female; fertile patients must use a reliable contraception method;
  • Age ≤ 75 yrs (children of any age are allowed in the protocol);
  • Informed consent given by patient or his/her guardian if of minor age.

Who cannot join

  • Any condition not fulfilling inclusion criteria;
  • HIV positive;
  • Non-hematological malignancy(ies) (except non-melanoma skin cancer) < 3 years before nonmyeloablative hematopoietic cell transplantation (HCT);
  • Life expectancy severely limited by disease other than malignancy;
  • Administration of cytotoxic agent(s) for "cytoreduction" within three weeks prior to initiating the nonmyeloablative transplant conditioning (Exceptions are hydroxyurea and imatinib mesylate);
  • CNS involvement with disease refractory to intrathecal chemotherapy;
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  • Terminal organ failure, except for renal failure (dialysis acceptable)
  • Cardiac: Symptomatic coronary artery disease or other cardiac failure requiring therapy; ejection fraction <35%; uncontrolled arrhythmia, uncontrolled hypertension;
  • Pulmonary: DLCO < 35% and/or receiving supplementary continuous oxygen;
  • Hepatic: Fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin >3 mg/dL, and symptomatic biliary disease;
  • Uncontrolled infection;
  • Karnofsky Performance Score <70%;
  • Patient is a fertile man or woman who is unwilling to use contraceptive techniques during and for 12 months following treatment;
  • Patient is a female who is pregnant or breastfeeding;
  • Any condition precluding the use of sirolimus or MMF;
  • One HLA mismatch with peripheral blood stem cells (PBSC) fit to/willing to donate.

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

Belgium13 sites

  • Ziekenhuis Netwerk Antwerpen (ZNA)

    Antwerp, Antwerpen, 2060

  • AZ Sint-Jan AV

    Bruges, West Flanders, 8000

  • Jules Bordet Institute

    Brussels, Brabant, 1000

  • AZ VUB Jette

    Brussels, Brussels Region Capital, 1090

  • Cliniques universitaires Saint-Luc- Université Catholique de Louvain

    Brussels, Brussels Region Capital, 1200

  • Queen Fabiola Children's University Hospital

    Brussels, Brussels, Region Capital, 1020

  • University Hospital, Antwerp

    Edegem, Antwerp, 2650

  • UZ Gent

    Ghent, Flanders Ost, 9000

  • Jolimont Hospital Haine Saint Paul

    Haine St-Paul, Hainaut, 7100

  • University Hospital, Gasthuisberg

    Leuven, Flamish Brabant, 3000

  • CHU Sart Tilman

    Liège, 4000

  • H.-Hart Hospital Roeselare-Menen

    Roeselare, Western Flanders, 8800

  • Cliniques Universitaires de Mont-Godinne

    Yvoir, Namur, 5530

Other trials in Belgium

About this study

Official title: Allogeneic Hematopoietic Cell Transplantation From HLA-matched Donors After Reduced-intensity Conditioning: a Phase II Randomized Study Comparing 2 GVHD Prophylaxis Regimens

The present project is a multicenter phase II trail aiming at comparing which of the two postgrafting immunosuppressive regimens proposed in this study will be best suited to prevent graft-versus-host disease (GVDH).

The immunosuppressive regimens will consist of: Tacrolimus plus Mycophenolate Mofetil or Tacrolimus plus Sirolimus. Before grafting patients will undergo a reduced-intensity conditioning with Fludarabine/total body irradiation (TBI) or Fludarabine/Busulfan/anti-thymoglobuline. Following the interim analysis of October 2014, the protocol has been amended to allow inclusion only after Flu-TBI conditioning. The hypothesis is that the Tacrolimus plus Sirolimus regimen will be associated with better progression-free survival due to a lower incidence of relapse/progression.

Keywords
Allogeneic hematopoeitic cell transplantation, Graft-Versus-Host Disease, Prophylaxis, Reduced-intensity conditioning, Immunosuppressive regimen, HLA-matched donor, Progression free survival, Overall survival
Medical subject headings
Graft vs Host Disease, Hematologic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Mycophenolate mofetilDrug

    Also called CellCept

    Tablets. For HLA-identical sibling donors:15 mg/kg t.i.d from day 0 to day 28. For alternative donor: 15 mg/kg, from day 0 to day 42.

  • SirolimusDrug

    Also called Rapamune

    Tablets. 6 mg loading dose on day -3, followed by (1)-2 mg daily to a target trough level of 5 to 10 ng/mL. Full doses will be given until day 100 (sibling recipients) or 180 (alternative donor recipients). Doses will then be progressively tapered to be definitely discontinued by day 180 (sibling donors) or 365 (alternative donor recipients) in the absence of GVHD.

Study groups in NCT01428973
Study groupRoleWhat they receive
Arm 1Active comparatorGVHD prophylaxis: Mycophenolate mofetil (MMF) orally from the evening of day 0 through day 28 (sibling recipients) or day 42 (alternative donor recipients) at the dose of 15 mg/kg t.i.d. Tacrolimus (Tac)given orally at the dose of 0.06 mg/kg bid starting on day -3. The dose adapted according to through whole blood values following standard procedures (between 10 and 15 ng/ml the first 28 days and between 5-10 ng/ml thereafter). Full doses given until day 100 (sibling recipients) or 180 (alternative donor recipients). Doses tapered to be definitely discontinued by day 180 (sibling donors) or 365 (alternative donor recipients) in the absence of GVHD.
Receives: Drug: Mycophenolate mofetil
Arm 2ExperimentalGVHD prophylaxis: Tacrolimus, orally (0.06 mg/kg) bid starting on day -3. The dose adapted between 5-10 ng/ml. Full doses until day 60 (sibling recipients) or day 100 (alternative donor recipients). Doses tapered to be definitely discontinued by day 100 (sibling donors) or 180 (alternative donor recipients) in the absence of GVHD. Sirolimus 6 mg loading dose on day -3, followed by (1)-2 mg daily to a target trough level of 5 to 10 ng/mL. Full doses until day 100 (sibling recipients) or 180 (alternative donor recipients). Doses will then be progressively tapered to be definitely discontinued by day 180 (sibling donors) or 365 (alternative donor recipients) in the absence of GVHD
Receives: Drug: Sirolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival

    To compare the 1-year progression-free survival between the 2 prophylactic arms (Tracolimus/Mycophenolate Mofetil and Tracolimus/Sirolimus) in the whole group of patients and separately in those conditioned with Fluradabine/TBI or Fluradabine plus Busulfan and anti-thymocyte globulin.

    Measured: 1 year after transplantation

Secondary outcomes (7)

  1. Relapse rate; nonrelapse mortality and overall survival

    To compare relapse rate, nonrelapse mortality, and overall survival in the 2 prophyltic arms (Tracolimus/Mycophenolate Mofetil and Tracolimus/Sirolimus) 1, 2 and 5 years after hematopietic stem cell transplantation (HSCT) in the whole group of patients and separately in those conditioned with Fluradabine/TBI or Fluradabine plus Busulfan and anti-thymocyte globulin.

    Measured: 1, 2 and 5 years after transplantation

  2. Progression free survival

    To compare progression-free survival in the 2 phrophylactic arms (Tracolimus/Mycophenolate Mofetil and Tracolimus/Sirolimus) 2 and 5 years after HSCT, in the whole group of patients and separately in those conditioned with Fluradabine/TBI or Fluradabine plus Busulfan and anti-thymocyte globulin.

    Measured: 2 and 5 years after transplantation

  3. Engraftment

    To compare hematopoietic (whole blood and T cell chimerism) engraftment and to evaluate the 1-year incidence of graft rejection in the 2 prophylctic arms (Tracolimus/Mycophenolate Mofetil and Tracolimus/Sirolimus), in the whole group of patients and separately in those conditioned with Fluradabine/TBI or Fluradabine plus Busulfan and anti-thymocyte globulin.

    Measured: 1 year after transplantation

  4. Acute GVDH

    To compare the 6-mo incidence of grades II-IV and III-IV acute GVHD in the 2 prophylactic arms (Tracolimus/Mycophenolate Mofetil and Tracolimus/Sirolimus), in the whole group of patients and separately in those conditioned with Fluradabine/TBI or Fluradabine plus Busulfan and anti-thymocyte globulin.

    Measured: 6 months after transplantation

  5. Chronic GVDH

    To compare the 1-yr incidence of chronic GVHD in the phrophylactic 2 prophylactic arms (Tracolimus/Mycophenolate Mofetil and Tracolimus/Sirolimus), in the whole group of patients and separately in those conditioned with Fluradabine/TBI or Fluradabine plus Busulfan and anti-thymocyte globulin.

    Measured: 1 year after transplantation

  6. Immunological reconstitution

    To compare the quality and timing of immunologic reconstitution in the 2 prophylactic arms (Tracolimus/Mycophenolate Mofetil and Tracolimus/Sirolimus),in the whole group of patients and separately in those conditioned with Fluradabine/TBI or Fluradabine plus Busulfan and anti-thymocyte globulin.

    Measured: 3 mo, 6 mo, 1 yr, 2 yrs and 5 yrs after transplantation

  7. Infection

    To compare the 1-yr incidences of bacterial, fungal and viral infections in the 2 prophylactic arms (Tracolimus/Mycophenolate Mofetil and Tracolimus/Sirolimus), in the whole group of patients and separately in those conditioned with Fluradabine/TBI or Fluradabine plus Busulfan and anti-thymocyte globulin.

    Measured: 1 year after transplantation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Sep 2011 (estimated)
  2. Study startSep 2011
  3. Primary completionDec 2024 (estimated)
  4. Study completionDec 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
200 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01428973
Sponsor's protocol ID
TJB1016P1
Status last verified
May 2024
First submitted
1 Sep 2011
Last updated
9 May 2024
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Mycophenolate mofetil and Sirolimus in people with Graft-Versus-Host Disease and Hematological Malignancies, run by University of Liege at 13 sites in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 9 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (time frame: 1 year after transplantation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01428973.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2024.

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