Dose-reduced Versus Standard Conditioning in MDS/sAML

Phase 3

Terminated

• Conditions: Myelodysplastic Syndromes; Secondary Acute Myeloid Leukemia
• Interventions: Other: Reduced Intensity Conditioning; Other: Myeloablative conditioning

• Registration Number: NCT01203228
• Lead Sponsor: European Society for Blood and Marrow Transplantation

Brief Summary

In this trial dose reduced conditioning is compared to standard conditioning followed by allogeneic stem cell transplantation from related or unrelated donors in patients with MDS or secondary AML.

Conditioning is the very high dose chemotherapy treatment that is given in the days before the stem cell transplant.

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2004-05
• Study First Submitted: 2010-09-15
• Study First Submitted QC: 2010-09-15
• Study First Posted: 2010-09-16
• Primary Completion: 2015-01
• Study Completion: 2015-02
• Status Verified: 2015-04
• Last Update Submitted: 2015-04-02
• Last Update Posted: 2015-04-03

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 129

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 anti¬gen-mismatch allowed):

• No major organ dysfunction.

• Written informed consent of the patient.

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
B	Reduced Intensity Conditioning	Reduced Intensity Conditioning
A	Myeloablative conditioning	Myeloablative conditioning

Primary Outcome Measures

Name	Time	Method
non-relapse mortality	every 6 months for safety and in the final analysis at one year after allogeneic stem cell transplantation

Secondary Outcome Measures

Name	Time	Method
organ related toxicity of conditioning	every 6 months for safety and in the final analysis at day +30 after allogeneic stem cell transplantation
Incidence of aGVHD	every 6 months for safety and in the final analysis at day +100 after allogeneic stem cell transplantation
incidence of cGVHD	every 6 months for safety and in the final analysis at one year after allogeneic stem cell transplantation
overall survival	every 6 months for safety and in the final analysis at 2 years after allogeneic stem cell transplantation
VOD	every 6 months for safety and in the final analysis at day +100 after allogeneic stem cell transplantation
event-free survival	every 6 months for safety and in the final analysis at 2 years after allogeneic stem cell transplantation
cumulative incidence of relapse	every 6 months for safety and in the final analysis at 2 years after allogeneic stem cell transplantation
infection incidence	every 6 months for safety and in the final analysis at day +100, 1 year and 2 years after allogeneic stem cell transplantation
Haematopoeitic recovery	every 6 months for safety and in the final analysis at day +30 after allogeneic stem cell transplantation

Trial Locations

Locations (10)

University Hospital; 🇩🇪 Tübingen, Germany

Martin-Luther-Universität Halle-Wittenberg; 🇩🇪 Halle, Germany

SPb State I. Pavlov Medical University; 🇷🇺 St. Petersburg, Russian Federation

UKSH Campus Kiel; 🇩🇪 Kiel, Germany

University Hospital Eppendorf; 🇩🇪 Hamburg, Germany

Radboud University MC; 🇳🇱 Nijmegen, Netherlands

Ospedale Maggiore di Milano; 🇮🇹 Milano, Italy

Santi Antonio e Biagio; 🇮🇹 Alessandria, Italy

Ospedale di Careggi; 🇮🇹 Firenze, Italy

Universitätsklinikum Munster; 🇩🇪 Munster, Germany