Dose-reduced Versus Standard Conditioning in MDS/sAML (RICMAC)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Pierre Fabre Medicament
Information provided by (Responsible Party):
European Group for Blood and Marrow Transplantation
ClinicalTrials.gov Identifier:
NCT01203228
First received: September 15, 2010
Last updated: August 16, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Myelodysplastic Syndromes
Secondary Acute Myeloid Leukemia
Other: Reduced Intensity Conditioning
Other: Myeloablative conditioning
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by European Group for Blood and Marrow Transplantation:

Primary Outcome Measures:
  • non-relapse mortality [ Time Frame: every 6 months for safety and in the final analysis at one year after allogeneic stem cell transplantation ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • Incidence of aGVHD [ Time Frame: every 6 months for safety and in the final analysis at day +100 after allogeneic stem cell transplantation ] [ Designated as safety issue: Yes ]
  • incidence of cGVHD [ Time Frame: every 6 months for safety and in the final analysis at one year after allogeneic stem cell transplantation ] [ Designated as safety issue: Yes ]
  • overall survival [ Time Frame: every 6 months for safety and in the final analysis at 2 years after allogeneic stem cell transplantation ] [ Designated as safety issue: Yes ]
  • event-free survival [ Time Frame: every 6 months for safety and in the final analysis at 2 years after allogeneic stem cell transplantation ] [ Designated as safety issue: Yes ]
  • cumulative incidence of relapse [ Time Frame: every 6 months for safety and in the final analysis at 2 years after allogeneic stem cell transplantation ] [ Designated as safety issue: Yes ]
  • VOD [ Time Frame: every 6 months for safety and in the final analysis at day +100 after allogeneic stem cell transplantation ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Haematopoeitic recovery [ Time Frame: every 6 months for safety and in the final analysis at day +30 after allogeneic stem cell transplantation ] [ Designated as safety issue: Yes ]

Enrollment: 129
Study Start Date: May 2004
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A
Myeloablative conditioning
Other: 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

Other Names:
  • Myleran
  • Sulphabutin
  • Busulphan
  • Leucosulfan
  • Myeloleukon
  • Citosulfan
  • Mielevcin
  • Milecitan
  • cyclophosphamide
  • Procytox
  • Cytoxan
  • Cyclophosphan
  • Cytophosphan
  • Claphene
  • Cyclostin
  • Endoxan
Experimental: B
Reduced Intensity Conditioning
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

Other Names:
  • Myleran
  • Sulphabutin
  • Busulphan
  • Leucosulfan
  • Myeloleukon
  • Citosulfan
  • Mielevcin
  • Milecitan
  • Fludara
  • Beneflur
  • Fludura
  • FAMP
  • 2-Fluoro-ara-AMP

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01203228

Locations
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, Germany
Italy
Santi Antonio e Biagio
Alessandria, Italy
Ospedale di Careggi
Firenze, Italy
Ospedale Maggiore di Milano
Milano, Italy
Netherlands
Radboud University MC
Nijmegen, Netherlands
Russian Federation
SPb State I. Pavlov Medical University
St. Petersburg, Russian Federation
Sponsors and Collaborators
European Group for Blood and Marrow Transplantation
Pierre Fabre Medicament
Investigators
Study Chair: Nicolaus Kröger, MD Universitätsklinikum Hamburg-Eppendorf
Principal Investigator: Axel R Zander, MD University Hospital Hamburg-Eppendorf, Germany
Principal Investigator: Ghulam J Mufti, MD King's College Hospital London, United Kingdom
Principal Investigator: Marie Robin, MD Hopital Saint-Louis Paris, France
Principal Investigator: Kathrin Haifa Al-Ali, MD University Hospital Leipzig, Germany
Principal Investigator: Dietger Niederwieser, MD University Hospital Leipzig, Germany
Principal Investigator: Giorgio Lambertenghi Deliliers IRCCS Ospedale Maggiore of Milan, Italy
Principal Investigator: Domink Heim, Prof. University Hospital, Basel, Switzerland
Principal Investigator: Liisa Volin, MD Helsinki University Central Hospital, Finland
Principal Investigator: Stefano Guidi, MD Careggi Hospital - Florence, Italy
Principal Investigator: Augustin Ferrant, MD Cliniques Universitaires St. Luc Bruxelles, Belgium
Principal Investigator: Afanasyer Boris SPB Pavlov Medical Univ, St. Petersburg, Russia
Principal Investigator: Kai Hubel University of Cologne, Germany
Principal Investigator: Peter Dreger Univ Hospital Heidelberg - Germany
Principal Investigator: Martin Gramatzlle University Hospital Münster - Germany
Principal Investigator: Gerhard Behre Martin-Luther-Universitaet Halle-Wittenberg - Germany
Principal Investigator: Martin Gramatzlle Univ Hospital Kiel - Germany
Principal Investigator: Allione Bernardino Santi Antonio E Biagio
  More Information

Additional Information:
No publications provided

Responsible Party: European Group for Blood and Marrow Transplantation
ClinicalTrials.gov Identifier: NCT01203228     History of Changes
Obsolete Identifiers: NCT00682396
Other Study ID Numbers: 2005-002011-24, EBMT 42205525
Study First Received: September 15, 2010
Last Updated: August 16, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ethics Committee
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Russia: Ethics Committee
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by European Group for Blood and Marrow Transplantation:
Reduced Intensity conditioning
Myeloablative conditionig
Allogeneic stem cell transplantation
MUD

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Busulfan
Cyclophosphamide
Fludarabine monophosphate
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antirheumatic Agents
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on July 23, 2014