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

October 11, 2022 updated by: Frédéric Baron, University of Liege

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)

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
114

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Frédéric Baron, MD,Ph
  • Phone Number: 0032497121806 +32 4 366 72 01
  • Email: F.Baron@uliege.be

Study Locations

  • Belgium
      • Antwerp, Belgium, 2060
      • Brugge, Belgium, 8000
      • Brussels, Belgium, 1090
      • Brussels, Belgium, 1000
      • Brussels, Belgium, 1200
      • Gent, Belgium, 9000
      • Leuven, Belgium, 3000
        • Recruiting
        • UZ Leuven
        • Contact:
        • Sub-Investigator:
          • Hélène Schoemans, MD PhD
      • Liège, Belgium, 4000
        • Recruiting
        • CHU de Liege
        • Sub-Investigator:
          • Evelyne Willems, MD
        • Contact:
          • Frédéric Baron, MD, PhD
          • Phone Number: +3243667201 +3243667201
          • Email: F.Baron@uliege.be
        • Contact:
        • Sub-Investigator:
          • Sophie Servais, MD
      • Roeselare, Belgium, 8800
      • Yvoir, Belgium, 5530

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Drug: Melphalan
100mg/m² on day -2
Other Names:
  • alkeran
Drug: Fludarabine
30mg/m² on days -6, -5, -4, -3, and -2
Drug: Cyclophosphamid
50 mg/kg on days +3 and +4.
Other Names:
  • PTCy
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.
Drug: Melphalan
100mg/m² on day -2
Other Names:
  • alkeran
Drug: Fludarabine
30mg/m² on days -6, -5, -4, -3, and -2
Drug: Thymoglobulin
ATG: 2.5 mg /kg/day on day -2 and -1 (day 0 is allogenic transplantation)
Other Names:
  • ATG

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Current GVHD-free, relapse-free survival (cGRFS)
Time Frame: 15 years (the primary endpoint will be first assessed after 191 events have been reached)
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
cGRFS according donor
Time Frame: 15 years
To assess cGRFS for patients conditioned with FM-PTCy or FM-ATG separately in those transplanted with a related or an unrelated donor
15 years
Relapse/progression rate
Time Frame: 15 years
To assess the relapse/progression rate for patients conditioned with FM-PTCy or FM-ATG
15 years
Rate aGVHD
Time Frame: 6 months
To assess rate of grade II-IV and III-IV acute GVHD (Graft-versus-host disease) in patients conditioned with FM or FM-ATG.
6 months
Rate cGVHD
Time Frame: 24 months
To assess rate of grade of moderate-severe chronic GVHD in patients conditioned with FM or FM-ATG.
24 months
Rate of Nonrelapse Mortality (NRM)
Time Frame: 15 years
To assess rate of Nonrelapse Mortality in patients conditioned with FM-PTCy or FM-ATG.
15 years
Rate of Leukemia Free Survival (LFS)
Time Frame: 15 years
To assess rate of Leukemia Free Survival in patients conditioned with FM-PTCy or FM-ATG.
15 years
Rate of Overall Survival (OS)
Time Frame: 15 years
To assess rate of Overall Survival in patients conditioned with FM-PTCy or FM-ATG.
15 years
Proportion of patients alive
Time Frame: 15 years
To assess the proportion of patients alive without active disease and without systemic immunosuppression
15 years

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Hematopoietic engraftment
Time Frame: 2 years
To assess hematopoietic (whole blood and T cell chimerism) engraftment in the 2 arms.
2 years
Quality of immunologic reconstitution
Time Frame: 5 years
To assess the quality of immunologic reconstitution in the 2 arms
5 years
Timing of immunologic reconstitution
Time Frame: 5 years
To assess the timing (days) of immunologic reconstitution in the 2 arms
5 years
Incidences of bacterial infections
Time Frame: 1 year
To assess the incidences of bacterial infections (number of episode, site, grade) in the 2 arms, in the whole group of patients
1 year
Incidences of fungal infections
Time Frame: 1 year
To assess the incidences of fungal infections (number of episode, site, grade) in the 2 arms, in the whole group of patients
1 year
Incidences of viral infections
Time Frame: 1 year
To assess the incidences of viral infections (number of episode, site, grade) in the 2 arms, in the whole group of patients
1 year
Assess Thymoglobulin (ATG) Pharmacokinetic
Time Frame: 10 days
To assess kinetics of functional ATG serum levels (mg/L) in the FM-ATG arm
10 days
Assess ATG Pharmacokinetic in association with cGRFS
Time Frame: 15 years
To assess kinetics of functional ATG serum levels (mg/L) in the FM-ATG arm in association with cGRFS
15 years
Assess ATG Pharmacokinetic in association with NRM
Time Frame: 15 years
To assess kinetics of functional ATG serum levels (mg/L) in the FM-ATG arm in association with NRM
15 years
Assess ATG Pharmacokinetic in association with OS
Time Frame: 15 years
To assess kinetics of functional ATG serum levels (mg/L) in the FM-ATG arm in association with OS
15 years
Assess ATG Pharmacokinetic in association with Relapse/progression
Time Frame: 15 years
To assess kinetics of functional ATG serum levels (mg/L) in the FM-ATG arm in association with Relapse/progression
15 years
Assess ATG Pharmacokinetic in association with Infections
Time Frame: 1 years
To assess kinetics of functional ATG serum levels (mg/L) in the FM-ATG arm in association with Infections
1 years
Assess ATG Pharmacokinetic in association with immunologic reconstitution
Time Frame: 5 years
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)
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Liege

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Belgian Hematological Society

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Frédéric Baron, MD,Ph, Centre Hospitalier Universitaire de Liege

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 4, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2033

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2038

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 21, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 20, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 25, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 12, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 11, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BHS-TC14
  • 2017-000824-91 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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