Dose-reduced Versus Standard Conditioning in MDS/sAML

Myelodysplastic Syndromes Clinical Trial

— RICMAC  

Official title:

Dose-reduced Versus Standard Conditioning Followed by Allogeneic Stem Cell Transplantation in Patients With MDS or sAML: A Randomised Phase III Study (RICMAC)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01203228
• Other study ID #: 2005-002011-24
• Secondary ID: EBMT 42205525
• Status: Terminated
• Phase: Phase 3
• First received: September 15, 2010
• Last updated: April 2, 2015
• Start date: May 2004
• Est. completion date: February 2015

Study information

• Verified date: April 2015
• Source: European Group for Blood and Marrow Transplantation
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsFinland: Finnish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesItaly: Ethics CommitteeNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Russia: Ethics CommitteeSwitzerland: SwissmedicUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT00682396

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 129
• Est. completion date: February 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia
• Secondary Acute Myeloid Leukemia

Intervention

Other:
• Reduced Intensity Conditioning
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 conditioning
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

Locations

Country	Name	City	State
Germany	University Hospital	Düsseldorf
Germany	Martin-Luther-Universität Halle-Wittenberg	Halle
Germany	University Hospital Eppendorf	Hamburg
Germany	University Hospital	Heidelberg
Germany	UKSH Campus Kiel	Kiel
Germany	University Hospital	Köln
Germany	University Hospital	Leipzig
Germany	Universitätsklinikum Munster	Munster
Germany	University Hospital	Tübingen
Italy	Santi Antonio e Biagio	Alessandria
Italy	Ospedale di Careggi	Firenze
Italy	Ospedale Maggiore di Milano	Milano
Netherlands	Radboud University MC	Nijmegen
Russian Federation	SPb State I. Pavlov Medical University	St. Petersburg

Sponsors (2)

Lead Sponsor	Collaborator
European Group for Blood and Marrow Transplantation	Pierre Fabre Medicament

Countries where clinical trial is conducted

Germany,  Italy,  Netherlands,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	non-relapse mortality		every 6 months for safety and in the final analysis at one year after allogeneic stem cell transplantation	Yes
Secondary	organ related toxicity of conditioning		every 6 months for safety and in the final analysis at day +30 after allogeneic stem cell transplantation	Yes
Secondary	Incidence of aGVHD		every 6 months for safety and in the final analysis at day +100 after allogeneic stem cell transplantation	Yes
Secondary	incidence of cGVHD		every 6 months for safety and in the final analysis at one year after allogeneic stem cell transplantation	Yes
Secondary	overall survival		every 6 months for safety and in the final analysis at 2 years after allogeneic stem cell transplantation	Yes
Secondary	event-free survival		every 6 months for safety and in the final analysis at 2 years after allogeneic stem cell transplantation	Yes
Secondary	cumulative incidence of relapse		every 6 months for safety and in the final analysis at 2 years after allogeneic stem cell transplantation	Yes
Secondary	VOD		every 6 months for safety and in the final analysis at day +100 after allogeneic stem cell transplantation	Yes
Secondary	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	Yes
Secondary	Haematopoeitic recovery		every 6 months for safety and in the final analysis at day +30 after allogeneic stem cell transplantation	Yes

External Links

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