Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Hematologic Neoplasms

Graft vs Host Disease

Disease Progression

Hematologic Diseases

Homologous Wasting Disease

Anti-Inflammatory Agents

All Drugs and Chemicals

Anti-Infective Agents

Antineoplastic Agents

Triamcinolone

Triamcinolone Acetonide

Triamcinolone hexacetonide

Triamcinolone diacetate

Mycophenolic Acid

Tacrolimus

Sirolimus

Immunosuppressive Agents

Temsirolimus

MTOR Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Enzyme Inhibitors

Clotrimazole

Miconazole

Antifungal Agents

Immunologic Factors

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.

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

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.

Mycophenolate mofetil

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.

Frédéric Baron, MD; PhD

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.

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

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

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.

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.

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.

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.

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.

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.

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.

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.

AZ Sint-Jan AV

Ziekenhuis Netwerk Antwerpen (ZNA)

Jules Bordet Institute

University Hospital, Gasthuisberg

AZ-VUB

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

University Hospital, Antwerp

Cliniques Universitaires de Mont-Godinne

Hospital de Jolimont

University Hospital, Ghent

AZ Delta

University of Liege

Prof

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Heart and Blood Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Influenza, Human

Lymphoma

Multiple Myeloma

Neoplasms, Plasma Cell

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Hodgkin Disease

Myeloproliferative Disorders

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Leukemia, B-Cell

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia

Hodgkin Lymphoma

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Antirheumatic Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Melphalan

Thymoglobulin

Antineoplastic Agents, Alkylating

Alkylating Agents

FM-PTCy conditioning will consist in IV fludarabine 30 mg/m2 on days -6, -5, -4, -3, and -2 (total dose 150 mg/m2), melphalan given at the dose of 100 mg/m2 on day -2, and cyclophosphamide 50 mg/kg on days +3 and +4.

FM-ATG conditioning will consist in IV fludarabine 30 mg/m2 on days -6, -5, -4, -3, and -2 (total dose 150 mg/m2), melphalan given at the dose of 100 mg/m2 on day -2, and ATG (Thymoglobulin®, Genzyme), at a dose of 2.5 mg/kg/d on days -2 and -1.

ATG: 2.5 mg /kg/day on day -2 and -1 (day 0 is allogenic transplantation)

Cyclophosphamid

Frédéric Baron, MD,Ph

Dimitri Breems, MD PhD

Dominik Selleslag, MD, PhD

Philippe Lewalle, MD PhD

Ann De Becker, MD PhD

Rik Schots, MD PhD

Xavier Poiré, MD

Tessa Kerre, MD PhD

Johan Maertens, MD PhD

Hélène Schoemans, MD PhD

Frédéric Baron, MD, PhD

Yves Beguin, MD, PhD

Evelyne Willems, MD

Sophie Servais, MD

Dries Deeren, MD

Carlos Graux, MD PhD

The present project aims at comparing two conditioning regimens (FM-PTCy vs FM-ATG). The hypothesis is that one or the two regimens will lead to a 2-year cGRFS rate improvement from 30% (the cGRFS rate with FM without ATG/PTCy) to 45% (Pick-a-winner phase 2 randomized study).

This study is a multicenter, randomized, open-label, phase II study pick-a-winner study, comparing 2 conditioning regimens. A total of 114 eligible patients with HLA-matched donors will be randomized 1:1 between the FM-PTCy arm and the FM-ATG arm, with stratification for donor type (related or unrelated). The recruitment period is 3 years with a 5-year follow-up plus a 10-year additional long-term follow-up (for GVHD status, disease status, second malignancy and QOL). The whole study will be completed within 18 years.

Allogeneic Hematopoietic Cell Transplantation From HLA-matched Donor After Flu-Mel-PTCy Versus Flu-Mel-ATG Reduced-intensity Conditioning

Allogeneic Hematopoietic Cell Transplantation From HLA-matched Donor After Flu-Mel-PTCy Versus Flu-Mel-ATG Reduced-intensity Conditioning: a Phase II Randomized Study From the Belgian Hematology Society (BHS)

To assess hematopoietic (whole blood and T cell chimerism) engraftment in the 2 arms.

To assess the quality of immunologic reconstitution in the 2 arms

To assess the timing (days) of immunologic reconstitution in the 2 arms

To assess the incidences of bacterial infections (number of episode, site, grade) in the 2 arms, in the whole group of patients

To assess the incidences of fungal infections (number of episode, site, grade) in the 2 arms, in the whole group of patients

To assess the incidences of viral infections (number of episode, site, grade) in the 2 arms, in the whole group of patients

To assess kinetics of functional ATG serum levels (mg/L) in the FM-ATG arm

To assess kinetics of functional ATG serum levels (mg/L) in the FM-ATG arm in association with cGRFS

To assess kinetics of functional ATG serum levels (mg/L) in the FM-ATG arm in association with NRM

To assess kinetics of functional ATG serum levels (mg/L) in the FM-ATG arm in association with OS

To assess kinetics of functional ATG serum levels (mg/L) in the FM-ATG arm in association with Relapse/progression

To assess kinetics of functional ATG serum levels (mg/L) in the FM-ATG arm in association with Infections

To assess kinetics of functional ATG serum levels (mg/L) in the FM-ATG arm in association with immunologic reconstitution (CD4 and NAIVE T cells counts)

To assess the current GVHD-free, relapse-free survival (cGRFS) for patients in the 2 arms

To assess cGRFS for patients conditioned with FM-PTCy or FM-ATG separately in those transplanted with a related or an unrelated donor

To assess the relapse/progression rate for patients conditioned with FM-PTCy or FM-ATG

To assess rate of grade II-IV and III-IV acute GVHD (Graft-versus-host disease) in patients conditioned with FM or FM-ATG.

To assess rate of grade of moderate-severe chronic GVHD in patients conditioned with FM or FM-ATG.

To assess rate of Nonrelapse Mortality in patients conditioned with FM-PTCy or FM-ATG.

To assess rate of Leukemia Free Survival in patients conditioned with FM-PTCy or FM-ATG.

To assess rate of Overall Survival in patients conditioned with FM-PTCy or FM-ATG.

To assess the proportion of patients alive without active disease and without systemic immunosuppression

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Minitransplants With HLA-matched Donors : Comparison Between 2 GVHD Prophylaxis Regimens	NCT01428973	Graft-Versus-Ho... Hematological M...	Mycophenolate m... Sirolimus	16 Years - 75 Years	University of Liege
Allogeneic Hematopoietic Cell Transplantation From HLA-matched Donor After Flu-Mel-PTCy Versus Flu-Mel-ATG Reduced-intensity Conditioning	NCT03852407	Acute Myeloid L... Myelodysplastic... Chronic Myeloid... Myeloproliferat... Myeloproliferat... Acute Lymphoid ... Multiple Myelom... Chronic Lymphoi... Non Hodgkin Lym... Hodgkin Lymphom...	Thymoglobulin Melphalan Fludarabine Cyclophosphamid	18 Years - 75 Years	University of Liege

Spots Global Cancer Trial Database for allogeneic hematopoeitic cell transplantation