Dose-reduced Versus Standard Conditioning in MDS/sAML (RICMAC)
This study is ongoing, but not recruiting participants.
Sponsor:
European Group for Blood and Marrow Transplantation
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: April 29, 2013
Last verified: April 2013
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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: | December 2014 |
| Estimated Primary Completion Date: | December 2013 (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:
|
|
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:
|
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
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: | April 29, 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 May 22, 2013