Dose-reduced Versus Standard Conditioning in MDS/sAML

Phase 3TerminatedNCT01203228

European Society for Blood and Marrow Transplantation129 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

129

Conditions

Myelodysplastic Syndromes Secondary Acute Myeloid Leukemia

Interventions

Reduced Intensity ConditioningOTHER

Busilvex®: 6.4 mg/kg IBW i. v. day -7: 0.8 mg/kg IBW x 4 (2 hour infusion every 6 hours) day -6: 0.8 mg/kg IBW x 4 (2 hour infusion every 6 hours) or (if i.v.-application is not available) Busulfan: 8.0 mg/kg BW p. o.: day -7: 4.0 mg/kg BW day -6: 4.0 mg/kg BW plus: Fludarabine: 5 x 30 mg/m² BS i. v.: day -7: 30 mg/m² BS day -6: 30 mg/m² BS day -5: 30 mg/m² BS day -4: 30 mg/m² BS day -3: 30 mg/m² BS

Myeloablative conditioningOTHER

Busilvex®: 12.8 mg/kg IBW i. v.; day -9: 0.8 mg/kg IBW x 4 (2 hour infusion every 6 hours) day -8: 0.8 mg/kg IBW x 4 (2 hour infusion every 6 hours) day -7: 0.8 mg/kg IBW x 4 (2 hour infusion every 6 hours) day -6: 0.8 mg/kg IBW x 4 (2 hour infusion every 6 hours) or (if i.v.-application is not available): Busulfan: 16.0 mg/kg BW p. o.; day -9: 4.0 mg/kg BW day -8: 4.0 mg/kg BW day -7: 4.0 mg/kg BW day -6: 4.0 mg/kg BW plus: Cyclophosphamide: 120 mg/kg BW i. v.; day -4: 60 mg/kg BW day -3: 60 mg/kg BW

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Locations (14)

University Hospital

Cologne, Germany

University Hospital

Düsseldorf, Germany

Martin-Luther-Universität Halle-Wittenberg

Halle, Germany

Outcomes

Primary Outcomes

non-relapse mortality

Time frame: every 6 months for safety and in the final analysis at one year after allogeneic stem cell transplantation

Secondary Outcomes

organ related toxicity of conditioning

Time frame: every 6 months for safety and in the final analysis at day +30 after allogeneic stem cell transplantation

Incidence of aGVHD

Time frame: every 6 months for safety and in the final analysis at day +100 after allogeneic stem cell transplantation

incidence of cGVHD

Time frame: every 6 months for safety and in the final analysis at one year after allogeneic stem cell transplantation

overall survival

Time frame: every 6 months for safety and in the final analysis at 2 years after allogeneic stem cell transplantation

event-free survival

Time frame: every 6 months for safety and in the final analysis at 2 years after allogeneic stem cell transplantation

cumulative incidence of relapse

Time frame: every 6 months for safety and in the final analysis at 2 years after allogeneic stem cell transplantation

VOD

Time frame: every 6 months for safety and in the final analysis at day +100 after allogeneic stem cell transplantation

infection incidence

Time frame: every 6 months for safety and in the final analysis at day +100, 1 year and 2 years after allogeneic stem cell transplantation

Data from ClinicalTrials.gov

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