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NCT06235398Not yet recruitingPhase 2

Upfront Related Donor Transplantation in Patients With Myelodisplatic Syndrome : a Phase 2 Trial

Source: ClinicalTrials.gov · Last updated 31 Jan 2024 · Not updated for over 12 months - ask the site whether it is still open

Brief summary (registry, in English)

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.

Status (registry)
Not yet recruiting
Phase (registry)
Phase 2
Study type
Interventional
Enrollment
55 (estimated)
First submitted
23 Jan 2024
Start date
1 Feb 2024
Primary completion date
1 Feb 2028
Lead sponsor
Assistance Publique - Hôpitaux de Paris
NCT number
NCT06235398

What you commit to

  • Study type: Interventional · Phase 2
  • Planned participants: 55
  • From 1 Feb 2024 to the primary completion date, 1 Feb 2028
  • No sites listed in no country
  • Visits and tests: ask the trial team, the registry does not list them

Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.

Who cannot take part

Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.

Prior treatment

  • Chemotherapy (AML like intensive chemotherapy or demethylating agent) to treat MDS at the current stage
  • Yellow fever vaccine or any alive vaccine within 2 months before transplantation

Other illness

  • Patient with uncontrolled infection
  • Cancer in the last 5 years (except basal cell carcinoma of the skin or "in situ" carcinoma of the cervix
  • 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
  • Who have any debilitating medical or psychiatric illness, which would preclude giving well understand informed consent or optimal treatment and follow-up

Lab values

  • Renal failure with creatinine clearance \<30ml / min (according to Cockroft formula)
  • Uncontrolled coronary insufficiency, recent myocardial infarction \<6 month, current manifestations of heart failure, uncontrolled cardiac rhythm disorders, ventricular ejection fraction \<50%

Other

  • 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)
  • Disponibility of an unrelated donor 10/10 (MUD) in absence of geno-identical donor
  • With contraindications to treatments used during the research
  • Pregnancy (β-HCG positive) or breast-feeding
  • Under protection by law (tutorship or curatorship)

Who the study is looking for

  • 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

Age in the registry: 50 years to 70 years · Sex: All · Does not accept healthy volunteers

Full criteria on ClinicalTrials.gov

This page is information, not medical advice. Discuss any trial with your doctor.