Myelodysplastic SyndromesPhase 2FIRST ALLO MDSNCT06235398
Upfront Related Donor Transplantation in Patients With Myelodisplatic Syndrome : a Phase 2 Trial
A Phase 2 study testing Hematopoietic stem-cell transplantation in people with Myelodysplastic Syndromes, run by Assistance Publique - Hôpitaux de Paris.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 50 to 70 years
- Conditions the study is for
- Myelodysplastic Syndromes
- What is being tested?
- Hematopoietic stem-cell transplantation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- No sites listed yet
- Study dates
- 1 Feb 2024to 1 Feb 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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):
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- 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
Who cannot join
- 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
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- 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)
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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.
- Conditions
- Myelodysplastic Syndromes
- Being tested
- Hematopoietic stem-cell transplantation
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hematopoietic stem-cell transplantationBiological
Upfront related donor transplantation
| Study group | Role | What they receive |
|---|---|---|
| Adults with Myelodysplasic Syndrome diagnosis | Experimental | Adults (Age ≥ 50 and ≤ 70 years) patients with MDS diagnosis for whom transplantation is indicated from a related donor identified. Receives: Biological: Hematopoietic stem-cell transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-free survival
Measured: 2 years after transplantation
Secondary outcomes (13)
Overall survival
Measured: 2 years after transplantation
Non-relapse mortality
Measured: 2 years after transplantation
Cumulative incidence of transformation into acute myeloid leukemia from inclusion
Measured: 2 years after inclusion
Incidence of acute Graft versus Host Disease (GvHD) and grading
Measured: 100 days after transplantation
Incidence of chronic GvHD and grading
Measured: 2 years after transplantation
Percentage of engraftment
Engraftment is defined by hematological recovery and donor chimerism > 95%
Measured: 3 months after transplantation
Percentage of graft failure
Graft failure is defined by acute or late rejection and non-engraftment
Measured: 2 years after transplantation
Incidence of severe infections
Severe infections are defined by Common Terminology of Adverse Events (CTAE) grade 3-4
Measured: 3 months after transplantation
Incidence of severe infections
Severe infections are defined by Common Terminology of Adverse Events grade 3-4
Measured: 6 months after transplantation
Incidence of severe infections
Severe infections are defined by Common Terminology of Adverse Events grade 3-4
Measured: 12 months after transplantation
Incidence of severe infections
Severe infections are defined by Common Terminology of Adverse Events grade 3-4
Measured: 24 months after transplantation
Incidence of cardiac events
CTAE grade 2-4
Measured: 1 month after transplantation
Incidence of cardiac events
CTAE grade 2-4
Measured: 3 months after transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2024
- Study start1 Feb 2024 (estimated)
- Primary completion1 Feb 2028 (estimated)
- Study completion1 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06235398
- Sponsor's protocol ID
- APHP221273
- Acronym
- FIRST ALLO MDS
- Status last verified
- Aug 2023
- First submitted
- 23 Jan 2024
- Last updated
- 31 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Upfront Related Donor Transplantation in Patients With Myelodisplatic Syndrome : a Phase 2 Trial
- ClinicalTrials.gov ID
- NCT06235398
- Acronym / sponsor ID
- FIRST ALLO MDS / APHP221273
- Conditions
- Myelodysplastic Syndromes
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 55 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 1 Feb 2024 (estimated)
- Primary completion
- 1 Feb 2028 (estimated)
- Study completion
- 1 Feb 2028 (estimated)
- First posted
- 31 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adults with Myelodysplasic Syndrome diagnosis | Experimental | Biological: Hematopoietic stem-cell transplantationAdults (Age ≥ 50 and ≤ 70 years) patients with MDS diagnosis for whom transplantation is indicated from a related donor identified. |
Who may qualify
- Ages
- 50 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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:
- Usual criteria for Hematopoietic Stem Cell Transplantation (HSCT):
- 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)
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hematopoietic stem-cell transplantationUpfront related donor transplantation | Biological | Adults with Myelodysplasic Syndrome diagnosis |
Primary outcome
Disease-free survival
Time frame: 2 years after transplantation
13 secondary outcomes
Overall survival
Time frame: 2 years after transplantation
Non-relapse mortality
Time frame: 2 years after transplantation
Cumulative incidence of transformation into acute myeloid leukemia from inclusion
Time frame: 2 years after inclusion
Incidence of acute Graft versus Host Disease (GvHD) and grading
Time frame: 100 days after transplantation
Incidence of chronic GvHD and grading
Time frame: 2 years after transplantation
Percentage of engraftment
Time frame: 3 months after transplantation
Percentage of graft failure
Time frame: 2 years after transplantation
Incidence of severe infections
Time frame: 3 months after transplantation
Incidence of severe infections
Time frame: 6 months after transplantation
Incidence of severe infections
Time frame: 12 months after transplantation
Incidence of severe infections
Time frame: 24 months after transplantation
Incidence of cardiac events
Time frame: 1 month after transplantation
Incidence of cardiac events
Time frame: 3 months after transplantation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hematopoietic stem-cell transplantation in people with Myelodysplastic Syndromes, run by Assistance Publique - Hôpitaux de Paris.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 31 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Marie Robin, Dr (+33142499639, marie.robin@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease-free survival (time frame: 2 years after transplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2024.