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

Study Purpose

The present project aims at comparing two conditioning regimens (FM-PTCy vs.#46;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).

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 75 Years
Gender All
More Inclusion & Exclusion 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) * 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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03852407
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of Liege
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Frédéric Baron, MD,Ph
Principal Investigator Affiliation Centre Hospitalier Universitaire de Liège
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherOther
Overall Status Recruiting
Countries Belgium
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

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
Additional Details

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.

Arms & Interventions

Arms

Experimental: 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.

Experimental: 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.

Interventions

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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

ZNA Stuivenberg, Antwerp, Belgium

Status

Not yet recruiting

Address

ZNA Stuivenberg

Antwerp, , 2060

Site Contact

Dimitri Breems, MD PhD

dimitri.Breems@zna.be

+32 4 366 72 01

AZ Sint Jan Brugge, Brugge, Belgium

Status

Recruiting

Address

AZ Sint Jan Brugge

Brugge, , 8000

Site Contact

Dominik Selleslag, MD, PhD

dominik.selleslag@AZsintjan.be

+32 4 366 72 01

IJ Bordet, Brussels, Belgium

Status

Not yet recruiting

Address

IJ Bordet

Brussels, , 1000

Site Contact

Philippe Lewalle, MD PhD

philippe.lewalle@bordet.be

+32 4 366 72 01

UZ Brussel, Brussels, Belgium

Status

Not yet recruiting

Address

UZ Brussel

Brussels, , 1090

Site Contact

Ann De Becker, MD PhD

ann.debecker@uzbrussel.be

+32 4 366 72 01

UCL St Luc, Brussels, Belgium

Status

Recruiting

Address

UCL St Luc

Brussels, , 1200

Site Contact

Xavier Poiré, MD

xavier.poire@uclouvain.be

+32 4 366 72 01

UZ Gent, Gent, Belgium

Status

Not yet recruiting

Address

UZ Gent

Gent, , 9000

Site Contact

Tessa Kerre, MD PhD

t.Kerre@UGent.be

+32 4 366 72 01

UZ Leuven, Leuven, Belgium

Status

Not yet recruiting

Address

UZ Leuven

Leuven, , 3000

Site Contact

Johan Maertens, MD PhD

johan.maertens@uzleuven.be

+32 4 366 72 01

CHU de Liège, Liège, Belgium

Status

Recruiting

Address

CHU de Liège

Liège, , 4000

Site Contact

Frédéric Baron, MD, PhD

F.Baron@uliege.be

+3243667201 #+3243667201

AZ Delta Roeselare, Roeselare, Belgium

Status

Not yet recruiting

Address

AZ Delta Roeselare

Roeselare, , 8800

Site Contact

Dries Deeren, MD

dries.deeren@AZdelta.be

+32 4 366 72 01

CHU UCL Namur Godinne, Yvoir, Belgium

Status

Not yet recruiting

Address

CHU UCL Namur Godinne

Yvoir, , 5530

Site Contact

Carlos Graux, MD PhD

carlos.graux@uclouvain.be

+32 4 366 72 01