Clinical trial NCT01428973: Minitransplants With HLA-matched Donors : Comparison Between 2 GVHD Prophylaxis Regimens
Official title: Allogeneic Hematopoietic Cell Transplantation From HLA-matched Donors After Reduced-intensity Conditioning: a Phase II Randomized Study Comparing 2 GVHD Prophylaxis Regimens
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Graft-Versus-Host Disease
Hematological Malignancies
Keywords: Allogeneic hematopoeitic cell transplantation
Graft-Versus-Host Disease
Prophylaxis
Reduced-intensity conditioning
Immunosuppressive regimen
HLA-matched donor
Progression free survival
Overall survival
Lead sponsor: University of Liege
Sponsor class: OTHER
Collaborators: name: AZ Sint-Jan AV
name: Ziekenhuis Netwerk Antwerpen (ZNA)
name: Jules Bordet Institute
name: University Hospital, Gasthuisberg
name: AZ-VUB
name: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
name: University Hospital, Antwerp
name: Cliniques Universitaires de Mont-Godinne
name: Hospital de Jolimont
name: University Hospital, Ghent
name: AZ Delta
First posted: 2011-09-05
Enrollment: 200
Sex: ALL
Minimum age (years): 16
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: Inclusion Criteria:

1. 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;
2. 10/10 HLA-A, -B, -C, DRB1 and DQBI allele-matched donor fit to/willing to donate PBSC.
3. Clinical situations:

   1. 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.
   2. Indication for a standard auto-transplant: perform mini-allotransplantation 2-6 months after standard autotransplant.
4. 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.

Exclusion Criteria:

* 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;
* Terminal organ failure, except for renal failure (dialysis acceptable)

  1. Cardiac: Symptomatic coronary artery disease or other cardiac failure requiring therapy; ejection fraction \<35%; uncontrolled arrhythmia, uncontrolled hypertension;
  2. Pulmonary: DLCO \< 35% and/or receiving supplementary continuous oxygen;
  3. 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.

Primary outcomes:
measure: Progression-free survival
timeFrame: 1 year after transplantation
Secondary outcomes:
measure: Relapse rate; nonrelapse mortality and overall survival
timeFrame: 1, 2 and 5 years after transplantation
measure: Progression free survival
timeFrame: 2 and 5 years after transplantation
measure: Engraftment
timeFrame: 1 year after transplantation
measure: Acute GVDH
timeFrame: 6 months after transplantation
measure: Chronic GVDH
timeFrame: 1 year after transplantation
measure: Immunological reconstitution
timeFrame: 3 mo, 6 mo, 1 yr, 2 yrs and 5 yrs after transplantation
measure: Infection
timeFrame: 1 year after transplantation
Other outcomes:
Locations:
city: Antwerpen,
country: Belgium
facility: Ziekenhuis Netwerk Antwerpen (ZNA)
state: Antwerpen
city: Edegem
country: Belgium
facility: University Hospital, Antwerp
state: Antwerp
city: Brussels
country: Belgium
facility: Jules Bordet Institute
state: Brabant
city: Brussels,
country: Belgium
facility: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
state: Brussels Region Capital
city: Brussels
country: Belgium
facility: AZ VUB Jette
state: Brussels Region Capital
city: Brussels
country: Belgium
facility: Queen Fabiola Children's University Hospital
state: Brussels, Region Capital
city: Leuven
country: Belgium
facility: University Hospital, Gasthuisberg
state: Flamish Brabant
city: Gent
country: Belgium
facility: UZ Gent
state: Flanders Ost
city: Haine St-Paul
country: Belgium
facility: Jolimont Hospital Haine Saint Paul
state: Hainaut
city: Yvoir
country: Belgium
facility: Cliniques Universitaires de Mont-Godinne
state: Namur
city: Brugge
country: Belgium
facility: AZ Sint-Jan AV
state: West Flanders
city: Roeselare
country: Belgium
facility: H.-Hart Hospital Roeselare-Menen
state: Western Flanders
city: Liège
country: Belgium
facility: CHU Sart Tilman
Study officials:
affiliation: University of Liege
name: Frédéric Baron, MD; PhD
role: PRINCIPAL_INVESTIGATOR
References: