Dose-reduced versus standard conditioning followed by allogeneic stem cell transplantation in patients with MDS or sAML: A randomised phase III study (RICMAC) - RICMAC MDS/sAML

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2005-002011-24-GB
• Date of registration: 16/04/2009
• Prospective Registration: Yes
• Primary sponsor: European Group for Blood and Marrow Transplantation
• Public title: Dose-reduced versus standard conditioning followed by allogeneic stem cell transplantation in patients with MDS or sAML: A randomised phase III study (RICMAC) - RICMAC MDS/sAML
• Scientific title: Dose-reduced versus standard conditioning followed by allogeneic stem cell transplantation in patients with MDS or sAML: A randomised phase III study (RICMAC) - RICMAC MDS/sAML
• Date of first enrolment: 21/04/2009
• Target sample size: 160
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-002011-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Finland, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
• Disease: Cytologically proven
• primary or therapy-related myelodysplastic syndrome (MDS), either as
? refractory anaemia (RA) according FAB or RA with or without dysplasia according WHO,
? refractory anaemia with ringsideroblasts (RARS) according FAB or RARS with or without dysplasia according WHO,
? refractory anaemia with excess of blasts (RAEB) according FAB or RAEB I or RAEB II according WHO,
? refractory anaemia with excess of blast in transformation (RAEB T) according FAB,
? CMML (dysplastic type) according WHO,
• or secondary acute myeloid leukaemia (sAML).
• Blast count < 20 percent in bone marrow with or without chemotherapy at time of transplantation.
• Patient eligible for standard and dose-reduced conditioning as per local guideline.
• Patient age 18 – 60 years if donor is a HLA-matched unrelated donor (HLA-A, HLA-B, HLA-DRB1 and HLA-DQB1) (one mismatch allowed):
• Patient age 18 – 65 years if donor is a HLA-matched related donor ((HLA-A, HLA-B, HLA-DRB1 and HLA-DQB1) (one antigen-mismatch allowed):
• No major organ dysfunction.
• Written informed consent of the patient.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Blasts > 20 % in bone marrow at time of transplantation
• No written informed consent.
• Central nervous involvement.
• Severe irreversible renal, hepatic, pulmonary or cardiac disease, such as
• Total bilirubin, SGPT or SGOT > 2 times upper the normal level.
• Left ventricular ejection fraction < 30 %.
• Creatinine clearance < 30 ml/min.
• DLCO < 35 % and/or receiving supplementary continuous oxygen.
• Positive serology for HIV.
• Pregnant or lactating women.
• Patients with a life-expectancy of less than six months because of another debilitating disease.
• Serious psychiatric or psychological disorders.
• Invasive fungal infection at time of registration.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

de novo-MDS, treatment-induced MDS (T MDS), AML arising from MDS, treatment-induced AML
MedDRA version: 9.1 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia
MedDRA version: 9.1 Level: LLT Classification code 10028533 Term: Myelodysplastic syndrome

Intervention(s)

Trade Name: Busilvex
Product Name: Bulsuphan
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: BUSULFAN
CAS Number: 55981
Concentration unit: mg milligram(s)

Trade Name: Fludara
Product Name: Fludarabine
Pharmaceutical Form: Powder for infusion*
INN or Proposed INN: FLUDARABINE
CAS Number: 21679141

Trade Name: Cyclophosphamide
Product Name: cyclophospamide
Product Code: PL 00116/0387
Pharmaceutical Form: Powder for injection*
INN or Proposed INN: CYCLOPHOSPHAMIDE
CAS Number: 50180

Primary Outcome(s)

Secondary Objective: •Comparison of haematopoietic recovery by day +30 post transplant between two arms.
•Comparison of toxicity of both regimens according to the Bearman-Score
•Incidence of acute graft-versus-host disease by day +100 post-transplant acc. to the Glucksberg scale
•Incidence of chronic graft-versus-host disease ("limited" or "extensive") by day +365 post-transplant as per to the criteria according to Shulman
•Comparison of overall survival post-transplant at two years.
•Comparison of event-free survival post-transplant at two years.
•Cumulative incidence of relapse post-transplant at two years between both groups.
•Comparison of VOD between the two arms
•Comparison of incidence of bacterial, viral, fungal and protozoal infection at day 100, at one year and at two years after transplantation.

Main Objective: The hypothesis is that a dose-reduced conditioning will reduce the non-relapse mortality from 40 % to 20 % at one year after allogeneic stem cell transplantation.

Primary end point(s): The hypothesis is that a dose-reduced conditioning will reduce the non-relapse mortality from 40 % to 20 % at one year after allogeneic stem cell transplantation.

Secondary ID(s)

2005-002011-24-FI

42205525

NCT00682396

Ethics review

Status: Approved
Approval date:
Contact: