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

NCT ID: NCT03852407

Last Updated: 2022-10-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 114 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-04
• Study Completion Date: 2038-11-01

Brief Summary

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).

Detailed Description

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.

Conditions

Acute Myeloid Leukemia in Remission; Myelodysplastic Syndromes; Chronic Myeloid Leukemia in Remission; Myeloproliferative Syndrome; Myeloproliferative Disorder; Acute Lymphoid Leukemia in Remission; Multiple Myeloma; Chronic Lymphoid Leukemia; Non Hodgkin Lymphoma; Hodgkin Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fludarabine-Melphalan-Cyclophosphamide

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.

Group Type: EXPERIMENTAL

Melphalan

Intervention Type: DRUG

100mg/m² on day -2

Fludarabine

Intervention Type: DRUG

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

Cyclophosphamid

Intervention Type: DRUG

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

Fludarabine-Melphalan-thymoglobulin

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.

Group Type: EXPERIMENTAL

Thymoglobulin

Intervention Type: DRUG

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

Melphalan

Intervention Type: DRUG

100mg/m² on day -2

Fludarabine

Intervention Type: DRUG

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

Interventions

Thymoglobulin

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

Intervention Type: DRUG

Melphalan

100mg/m² on day -2

Intervention Type: DRUG

Fludarabine

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

Intervention Type: DRUG

Cyclophosphamid

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

Intervention Type: DRUG

Other Intervention Names

ATG; alkeran; PTCy

Eligibility Criteria

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)

• 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.

• 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

• Unable to undergo leukapheresis because of poor vein access or other reasons.

Exclusion Criteria

Patients

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Belgian Hematological Society

OTHER

Sponsor Role: collaborator

University of Liege

OTHER

Sponsor Role: lead

Responsible Party

Frédéric Baron

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Frédéric Baron, MD,Ph

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire de Liege

Locations

ZNA Stuivenberg

Antwerp, , Belgium

Site Status: RECRUITING

AZ Sint Jan Brugge

Bruges, , Belgium

Site Status: RECRUITING

IJ Bordet

Brussels, , Belgium

Site Status: RECRUITING

UZ Brussel

Brussels, , Belgium

Site Status: RECRUITING

UCL St Luc

Brussels, , Belgium

Site Status: RECRUITING

UZ Gent

Ghent, , Belgium

Site Status: RECRUITING

UZ Leuven

Leuven, , Belgium

Site Status: RECRUITING

CHU de Liège

Liège, , Belgium

Site Status: RECRUITING

AZ Delta Roeselare

Roeselare, , Belgium

Site Status: RECRUITING

CHU UCL Namur Godinne

Yvoir, , Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Frédéric Baron, MD,Ph

Role: CONTACT

F.Baron@uliege.be

+32 4 366 72 01 ext. 0032497121806

Facility Contacts

Dimitri Breems, MD PhD

Role: primary

dimitri.Breems@zna.be

Dominik Selleslag, MD, PhD

Role: primary

dominik.selleslag@AZsintjan.be

Philippe Lewalle, MD PhD

Role: primary

philippe.lewalle@bordet.be

Ann De Becker, MD PhD

Role: primary

ann.debecker@uzbrussel.be

Xavier Poiré, MD

Role: primary

xavier.poire@uclouvain.be

Tessa Kerre, MD PhD

Role: primary

t.Kerre@UGent.be

Johan Maertens, MD PhD

Role: primary

johan.maertens@uzleuven.be

Frédéric Baron, MD, PhD

Role: primary

F.Baron@uliege.be

+3243667201 ext. +3243667201

Yves Beguin, MD, PhD

Role: backup

yves.beguin@chuliege.be

+3243667201 ext. +3243667201

Dries Deeren, MD

Role: primary

dries.deeren@AZdelta.be

Carlos Graux, MD PhD

Role: primary

carlos.graux@uclouvain.be

Other Identifiers

2017-000824-91

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BHS-TC14

Identifier Type: -

Identifier Source: org_study_id