Upfront Related Donor Transplantation in Patients With Myelodisplatic Syndrome : a Phase 2 Trial (FIRST ALLO MDS)

January 23, 2024 updated by: Assistance Publique - Hôpitaux de Paris
Three recent prospective "transplant/no transplant" studies concluded to an advantage of OS with transplantation in patients with high or intermediate-2 IPSS risk (not significant in Kröger's study). No prospective randomized trial has assessed the pre-transplant therapy in MDS patients yet but some information can be extracted from these 3 recent studies. In the French study (n=162), 72% patients with a donor received HSCT, previously treated by hypomethylating agent (HMA) in 71% of them. There was a trend to a better survival in patients achieving a complete remission with pre-graft therapy (HR: 0.55, p=0.088) and higher risk of death in unresponsiveness patients transformed into AML (HR: 2.36, p=0.008). In Nakamura's study (n=384), 83% of patients with a donor were transplanted, previously treated by HMA in 68%2. The multivariable Cox model for Overall Survival (OS) and Leukemia-free survival showed an excess risk in patients treated by HMA. Moreover, responders still have a higher risk of mortality as compared to patients who did not receive any pre-graft therapy (HR: 2.417, p=0.0054). In the German study, the aim was to initiate azacytidine at inclusion and to transplant patients after 4 cycles if a donor was identified1. Among 170 registered patients, 162 initiated 5-aza but 36% of them were "lost during this pre-graft therapy" before allocation to "donor" or "no-donor" arm, for different reasons including death (n=12). After 4 cycles of 5-aza, 79/81 patients "donor arm" were transplanted. The multivariable analysis showed remission status did not influence OS. Those 3 previous clinical trials thus suggest that a substantial number of patients planned for transplantation are not transplanted nowadays while no evidence of HMA benefit before HSCT has been clearly identified. This phase 2 study aim to assess the feasibility of upfront HSCT in patients with high risk MDS in order to increase the probability to be transplanted and to achieve a subsequent remission and better survival.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet 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.

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 (Estimated)

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.
55

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.

Study Contact Backup

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥ 50 and ≤ 70 years
  • An HLA (Human Leukocyte Antigen) matched sibling donor or familial haplo-identical donor has been identified

  • The disease fulfills at least one of the following criteria:

    • Intermediate-2 or high risk according to classical International Prognostic Scoring System (IPSS)
    • Intermediate-1 risk if marrow fibrosis > grade I or poor risk cytogenetics according to R IPSS or classified high or very high risk according to Revised International Prognostic Scoring System (R IPSS) or if the MDS is therapy-related neoplasm

  • Usual criteria for Hematopoietic Stem Cell Transplantation (HSCT):

    • Eastern Cooperative Oncology Group Score (ECOG) ≤ 2
    • No severe and uncontrolled infection
    • Cardiac function compatible with high dose of cyclophosphamide Left Ventricular Function (LVF) > 50%
    • Adequate organ function: ASAT and ALAT ≤ 2.5N, total bilirubin ≤ 2N, creatinine clearance ≥ 30 ml/min (according to Cockroft formula)
  • In case of transplantation with a haploidentical donor, absence of donor specific antibody (DSA) detected in the patient with a MFI >1000 (antibodies directed towards the distinct haplotype between donor and recipient)
  • Contraception methods must be prescribed for women of childbearing age during all the study. If cyclophosphamide is used, effective contraceptive methods for men during all their participation in the study
  • With health insurance coverage
  • With a written informed consent signed

Exclusion Criteria:

  • Marrow blast > 15% at time of inclusion
  • MDS with excess blast >10% and NPM1 mutation or a recurrent genetic abnormality related to Acute Myeloid Leukemia (AML) (WHO 2022)
  • Chemotherapy (AML like intensive chemotherapy or demethylating agent) to treat MDS at the current stage
  • Disponibility of an unrelated donor 10/10 (MUD) in absence of geno-identical donor
  • Patient with uncontrolled infection
  • Cancer in the last 5 years (except basal cell carcinoma of the skin or "in situ" carcinoma of the cervix
  • Renal failure with creatinine clearance <30ml / min (according to Cockroft formula)
  • With contraindications to treatments used during the research
  • Uncontrolled coronary insufficiency, recent myocardial infarction <6 month, current manifestations of heart failure, uncontrolled cardiac rhythm disorders, ventricular ejection fraction <50%
  • With heart failure according to NYHA (II or more)
  • Patient with seropositivity for HIV or HTLV-1 or active hepatitis B or C defined by a positive PCR Hepatitis B Virus or Hepatitis C Virus
  • Yellow fever vaccine or any alive vaccine within 2 months before transplantation
  • Pregnancy (β-HCG positive) or breast-feeding
  • Who have any debilitating medical or psychiatric illness, which would preclude giving well understand informed consent or optimal treatment and follow-up
  • Under protection by law (tutorship or curatorship)

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: N/A
  • Interventional Model: Single Group 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: Adults with Myelodysplasic Syndrome diagnosis
Adults (Age ≥ 50 and ≤ 70 years) patients with MDS diagnosis for whom transplantation is indicated from a related donor identified.
Biological: Hematopoietic stem-cell transplantation
Upfront related donor transplantation

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
Time Frame
Disease-free survival
Time Frame: 2 years after transplantation
2 years after transplantation

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
Overall survival
Time Frame: 2 years after transplantation
2 years after transplantation
Non-relapse mortality
Time Frame: 2 years after transplantation
2 years after transplantation
Cumulative incidence of transformation into acute myeloid leukemia from inclusion
Time Frame: 2 years after inclusion
2 years after inclusion
Incidence of acute Graft versus Host Disease (GvHD) and grading
Time Frame: 100 days after transplantation
100 days after transplantation
Incidence of chronic GvHD and grading
Time Frame: 2 years after transplantation
2 years after transplantation
Percentage of engraftment
Time Frame: 3 months after transplantation
Engraftment is defined by hematological recovery and donor chimerism > 95%
3 months after transplantation
Percentage of graft failure
Time Frame: 2 years after transplantation
Graft failure is defined by acute or late rejection and non-engraftment
2 years after transplantation
Incidence of severe infections
Time Frame: 3 months after transplantation
Severe infections are defined by Common Terminology of Adverse Events (CTAE) grade 3-4
3 months after transplantation
Incidence of severe infections
Time Frame: 6 months after transplantation
Severe infections are defined by Common Terminology of Adverse Events grade 3-4
6 months after transplantation
Incidence of severe infections
Time Frame: 12 months after transplantation
Severe infections are defined by Common Terminology of Adverse Events grade 3-4
12 months after transplantation
Incidence of severe infections
Time Frame: 24 months after transplantation
Severe infections are defined by Common Terminology of Adverse Events grade 3-4
24 months after transplantation
Incidence of cardiac events
Time Frame: 1 month after transplantation
CTAE grade 2-4
1 month after transplantation
Incidence of cardiac events
Time Frame: 3 months after transplantation
CTAE grade 2-4
3 months after transplantation

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.
Assistance Publique - Hôpitaux de Paris

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 (Estimated)

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 1, 2024

Primary Completion (Estimated)

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.
February 1, 2028

Study Completion (Estimated)

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.
February 1, 2028

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 23, 2024

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.
January 23, 2024

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.
January 31, 2024

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.
January 31, 2024

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.
January 23, 2024

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.
August 1, 2023

More Information

Terms related to this study

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.
  • APHP221273

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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