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RECRUITINGPhase 2INTERVENTIONAL

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)

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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).

Who May Be Eligible (Plain English)

Who May Qualify: Patients V.1.1. Diseases Hematological malignancies confirmed histologically: - AML in morphological CR or not in morphological CR but not rapidly progressing (i.e. no need to give treatments such as hydroxyurea to maintain WBC count \< 10 000 x109/mL); - MDS; - CML in CP or AP; - MPD not in blast crisis, - MDS/MPD overlap, - ALL in CR; - Multiple myeloma; - CLL; - Non-Hodgkin's lymphoma (aggressive NHL should have chemosensitive disease); - Hodgkin's disease with chemosensitive disease or responding to checkpoint inhibitors. \* Clinical situations • Theoretical indication for a standard allo-transplant, but not feasible because: - Age \> 50 yrs; - Unacceptable end organ performance; - The physician's decision; - The patient's decision - Underlying 'lower risk' disease, for which Reduced Intensity Conditioning is preferred (eg CLL, MCL) \* Other inclusion criteria - Male or female; fertile patients must use a reliable contraception method; - Age 18-75 yrs (children of any age are not allowed in the protocol); - willing to sign a consent form given by patient or his/her guardian if indicated. Donors - Male or female; - Any age; - Human Leukocyte Antigen (HLA)-identical sibling donor or 10 of 10 (HLA-A, -B, -C, -DRB1, and -DQB1) HLA allele matched unrelated donor; - Weight \> 15 Kg (because of leukapheresis); - Fulfills criteria for allogeneic Peripheral Blood Stem Cell (PBSC) donation according to standard procedures; - willing to sign a consent form given by donor or his/her guardian if indicated, as per donor center standard procedures. Who Should NOT Join This Trial: Patients - Any condition not fulfilling inclusion criteria; - Human weakened immune system Virus positive; - Non-hematological malignancy(ies) (except non-melanoma skin cancer) active \< 3 years before Hematopoietic Cell Transplantation (HCT). - Life expectancy severely limited by disease other than malignancy; ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: Patients V.1.1. Diseases Hematological malignancies confirmed histologically: * AML in morphological CR or not in morphological CR but not rapidly progressing (i.e. no need to give treatments such as hydroxyurea to maintain WBC count \< 10 000 x109/mL); * MDS; * CML in CP or AP; * MPD not in blast crisis, * MDS/MPD overlap, * ALL in CR; * Multiple myeloma; * CLL; * Non-Hodgkin's lymphoma (aggressive NHL should have chemosensitive disease); * Hodgkin's disease with chemosensitive disease or responding to checkpoint inhibitors. \* Clinical situations • Theoretical indication for a standard allo-transplant, but not feasible because: * Age \> 50 yrs; * Unacceptable end organ performance; * The physician's decision; * The patient's decision * Underlying 'lower risk' disease, for which Reduced Intensity Conditioning is preferred (eg CLL, MCL) \* Other inclusion criteria * Male or female; fertile patients must use a reliable contraception method; * Age 18-75 yrs (children of any age are not allowed in the protocol); * Informed consent given by patient or his/her guardian if indicated. Donors * Male or female; * Any age; * Human Leukocyte Antigen (HLA)-identical sibling donor or 10 of 10 (HLA-A, -B, -C, -DRB1, and -DQB1) HLA allele matched unrelated donor; * Weight \> 15 Kg (because of leukapheresis); * Fulfills criteria for allogeneic Peripheral Blood Stem Cell (PBSC) donation according to standard procedures; * Informed consent given by donor or his/her guardian if indicated, as per donor center standard procedures. Exclusion Criteria: Patients * Any condition not fulfilling inclusion criteria; * Human Immunodeficiency Virus positive; * Non-hematological malignancy(ies) (except non-melanoma skin cancer) active \< 3 years before Hematopoietic Cell Transplantation (HCT). * Life expectancy severely limited by disease other than malignancy; * Central Nervous System involvement with disease refractory to intrathecal chemotherapy. * Terminal organ failure, except for renal failure (dialysis acceptable) 1. Cardiac: Symptomatic coronary artery disease; ejection fraction \<40%; uncontrolled arrhythmia, uncontrolled hypertension; 2. Pulmonary: Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)\< 40% and/or receiving supplementary continuous oxygen, Forced Expiratory Volume in 1 Second (FEV1)\< 40%; 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 melphalan or Thymoglobulin; Donors * Any condition not fulfilling inclusion criteria; * Unable to undergo leukapheresis because of poor vein access or other reasons.

Treatments Being Tested

DRUG

Thymoglobulin

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

DRUG

Melphalan

100mg/m² on day -2

DRUG

Fludarabine

30mg/m² on days -6, -5, -4, -3, and -2

DRUG

Cyclophosphamid

50 mg/kg on days +3 and +4.

Locations (10)

ZNA Stuivenberg
Antwerp, Belgium
AZ Sint Jan Brugge
Bruges, Belgium
IJ Bordet
Brussels, Belgium
UZ Brussel
Brussels, Belgium
UCL St Luc
Brussels, Belgium
UZ Gent
Ghent, Belgium
UZ Leuven
Leuven, Belgium
CHU de Liège
Liège, Belgium
AZ Delta Roeselare
Roeselare, Belgium
CHU UCL Namur Godinne
Yvoir, Belgium