NCT01428973

Brief 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). 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.

Trial Health

55
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
200

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Sep 2011

Longer than P75 for phase_2

Geographic Reach
1 country

13 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 1, 2011

Completed
Same day until next milestone

Study Start

First participant enrolled

September 1, 2011

Completed
4 days until next milestone

First Posted

Study publicly available on registry

September 5, 2011

Completed
13.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2024

Completed
Last Updated

May 9, 2024

Status Verified

May 1, 2024

Enrollment Period

13.3 years

First QC Date

September 1, 2011

Last Update Submit

May 8, 2024

Conditions

Graft-Versus-Host DiseaseHematological Malignancies

Keywords

Allogeneic hematopoeitic cell transplantationGraft-Versus-Host DiseaseProphylaxisReduced-intensity conditioningImmunosuppressive regimenHLA-matched donorProgression free survivalOverall survival

Outcome Measures

Primary Outcomes (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.

    1 year after transplantation

Secondary Outcomes (7)

  • Relapse rate; nonrelapse mortality and overall survival

    1, 2 and 5 years after transplantation

  • Progression free survival

    2 and 5 years after transplantation

  • Engraftment

    1 year after transplantation

  • Acute GVDH

    6 months after transplantation

  • Chronic GVDH

    1 year after transplantation

  • +2 more secondary outcomes

Study Arms (2)

Arm 1

ACTIVE COMPARATOR

GVHD 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.

Drug: Mycophenolate mofetil

Arm 2

EXPERIMENTAL

GVHD 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

Drug: Sirolimus

Interventions

Mycophenolate mofetilDRUG

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.

Also known as: CellCept
Arm 1
SirolimusDRUG

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.

Also known as: Rapamune
Arm 2

Eligibility Criteria

Age16 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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;
  • 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 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;
  • +6 more criteria

You may not qualify if:

  • 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;
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (13)

Ziekenhuis Netwerk Antwerpen (ZNA)

Antwerp, Antwerpen, 2060, Belgium

Location

University Hospital, Antwerp

Edegem, Antwerp, 2650, Belgium

Location

Jules Bordet Institute

Brussels, Brabant, 1000, Belgium

Location

AZ VUB Jette

Brussels, Brussels Region Capital, 1090, Belgium

Location

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Brussels, Brussels Region Capital, 1200, Belgium

Location

Queen Fabiola Children's University Hospital

Brussels, Brussels, Region Capital, 1020, Belgium

Location

University Hospital, Gasthuisberg

Leuven, Flamish Brabant, 3000, Belgium

Location

UZ Gent

Ghent, Flanders Ost, 9000, Belgium

Location

Jolimont Hospital Haine Saint Paul

Haine St-Paul, Hainaut, 7100, Belgium

Location

Cliniques Universitaires de Mont-Godinne

Yvoir, Namur, 5530, Belgium

Location

AZ Sint-Jan AV

Bruges, West Flanders, 8000, Belgium

Location

H.-Hart Hospital Roeselare-Menen

Roeselare, Western Flanders, 8800, Belgium

Location

CHU Sart Tilman

Liège, 4000, Belgium

Location

MeSH Terms

Conditions

Graft vs Host DiseaseHematologic Neoplasms

Interventions

Mycophenolic AcidSirolimus

Condition Hierarchy (Ancestors)

Immune System DiseasesNeoplasms by SiteNeoplasmsHematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

CaproatesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsFatty AcidsLipidsMacrolidesLactones

Study Officials

  • Frédéric Baron, MD; PhD

    University of Liege

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prof

Study Record Dates

First Submitted

September 1, 2011

First Posted

September 5, 2011

Study Start

September 1, 2011

Primary Completion

December 1, 2024

Study Completion

December 1, 2024

Last Updated

May 9, 2024

Record last verified: 2024-05

Locations

BE(13)