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

NCT03852407 | Recruiting Phase 2

• 2 other identifiers: BHS-TC142017-000824-91
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 10

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).

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

Keywords

hematological malignancies; Graft versus host disease; GVHD; Progression free survival; Allogeneic hematopoeitic cell transplantation; HLA-matched donor; reduced intensity conditioning; Overall survival; ATG PK; Immunosuppressive regimen; Prophylaxis

Outcome Measures

Primary Outcomes (1)

• Current GVHD-free, relapse-free survival (cGRFS)

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

  15 years (the primary endpoint will be first assessed after 191 events have been reached)

Secondary Outcomes (8)

• cGRFS according donor

  15 years

• Relapse/progression rate

  15 years

• Rate aGVHD

  6 months

• Rate cGVHD

  24 months

• Rate of Nonrelapse Mortality (NRM)

  15 years

Other Outcomes (13)

• Hematopoietic engraftment

  2 years

• Quality of immunologic reconstitution

  5 years

• Timing of immunologic reconstitution

  5 years

Study Arms (2)

Fludarabine-Melphalan-Cyclophosphamide

EXPERIMENTAL

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.

Drug: Melphalan; Drug: Fludarabine; Drug: Cyclophosphamid

Fludarabine-Melphalan-thymoglobulin

EXPERIMENTAL

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.

Drug: Thymoglobulin; Drug: Melphalan; Drug: Fludarabine

Interventions

Thymoglobulin DRUG

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

Also known as: ATG

Fludarabine-Melphalan-thymoglobulin

Melphalan DRUG

100mg/m² on day -2

Also known as: alkeran

Fludarabine-Melphalan-Cyclophosphamide; Fludarabine-Melphalan-thymoglobulin

Fludarabine DRUG

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

Fludarabine-Melphalan-Cyclophosphamide; Fludarabine-Melphalan-thymoglobulin

Cyclophosphamid DRUG

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

Also known as: PTCy

Fludarabine-Melphalan-Cyclophosphamide

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• Patients
• 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)
• Cardiac: Symptomatic coronary artery disease; ejection fraction \<40%; uncontrolled arrhythmia, uncontrolled hypertension;
• 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%;
• 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

Sponsors & Collaborators

• University of Liege: lead
• Belgian Hematological Society: collaborator

Study Sites (10)

ZNA Stuivenberg

Antwerp, 2060, Belgium

RECRUITING

AZ Sint Jan Brugge

Bruges, 8000, Belgium

RECRUITING

IJ Bordet

Brussels, 1000, Belgium

RECRUITING

UZ Brussel

Brussels, 1090, Belgium

RECRUITING

UCL St Luc

Brussels, 1200, Belgium

RECRUITING

UZ Gent

Ghent, 9000, Belgium

RECRUITING

UZ Leuven

Leuven, 3000, Belgium

RECRUITING

CHU de Liège

Liège, 4000, Belgium

RECRUITING

AZ Delta Roeselare

Roeselare, 8800, Belgium

RECRUITING

CHU UCL Namur Godinne

Yvoir, 5530, Belgium

RECRUITING

MeSH Terms

Conditions

Myelodysplastic Syndromes; Myeloproliferative Disorders; Multiple Myeloma; Leukemia, B-Cell; Lymphoma, Non-Hodgkin; Hodgkin Disease; Hematologic Neoplasms; Graft vs Host Disease

Interventions

thymoglobulin; Melphalan; fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Lymphatic Diseases; Lymphoma; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds

Study Officials

• Frédéric Baron, MD,Ph

  Centre Hospitalier Universitaire de Liege

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Frédéric Baron, MD,Ph

CONTACT

+32 4 366 72 01; F.Baron@uliege.be

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 21, 2019
• First Posted: February 25, 2019
• Study Start: February 4, 2019
• Primary Completion (Estimated): November 1, 2033
• Study Completion (Estimated): November 1, 2038
• Last Updated: October 12, 2022

Record last verified: 2022-10

Locations

BE (10)