Myelodysplastic SyndromesPhase 3RICMACNCT01203228
Dose-reduced Versus Standard Conditioning in MDS/sAML
A Phase 3 study testing Reduced Intensity Conditioning and Myeloablative conditioning in people with Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia, run by European Society for Blood and Marrow Transplantation at 14 sites in 4 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Myelodysplastic Syndromes, Secondary Acute Myeloid Leukemia
- What is being tested?
- Reduced Intensity Conditioning and Myeloablative conditioning
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 129 participants
- Where
- 14 sitesin 4 countries
- Study dates
- May 2004to Feb 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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,
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- 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.
Who cannot join
- 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 %.
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- 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.
Trial locations and contacts
14 sites in 4 countries.
14 sites in 4 countries
Germany9 sites
University Hospital
Cologne
University Hospital
Düsseldorf
Martin-Luther-Universität Halle-Wittenberg
Halle
University Hospital Eppendorf
Hamburg
University Hospital
Heidelberg
UKSH Campus Kiel
Kiel
University Hospital
Leipzig
Universitätsklinikum Munster
Münster
University Hospital
Tübingen
Italy3 sites
Santi Antonio e Biagio
Alessandria
Ospedale di Careggi
Florence
Ospedale Maggiore di Milano
Milan
About this study
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)
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.
- Being tested
- Reduced Intensity Conditioning, Myeloablative conditioning
- Keywords
- Reduced Intensity conditioning, Myeloablative conditionig, Allogeneic stem cell transplantation, MUD
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Reduced Intensity ConditioningOther
Also called Myleran, Sulphabutin, Busulphan, Leucosulfan
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
Also called Myleran, Sulphabutin, Busulphan, Leucosulfan
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
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | Myeloablative conditioning Receives: Other: Myeloablative conditioning |
| B | Experimental | Reduced Intensity Conditioning Receives: Other: Reduced Intensity Conditioning |
What is being measured
The primary outcome is the main question the study is designed to answer.
non-relapse mortality
Measured: every 6 months for safety and in the final analysis at one year after allogeneic stem cell transplantation
Secondary outcomes (9)
organ related toxicity of conditioning
Measured: every 6 months for safety and in the final analysis at day +30 after allogeneic stem cell transplantation
Incidence of aGVHD
Measured: every 6 months for safety and in the final analysis at day +100 after allogeneic stem cell transplantation
incidence of cGVHD
Measured: every 6 months for safety and in the final analysis at one year after allogeneic stem cell transplantation
overall survival
Measured: every 6 months for safety and in the final analysis at 2 years after allogeneic stem cell transplantation
event-free survival
Measured: every 6 months for safety and in the final analysis at 2 years after allogeneic stem cell transplantation
cumulative incidence of relapse
Measured: every 6 months for safety and in the final analysis at 2 years after allogeneic stem cell transplantation
VOD
Measured: every 6 months for safety and in the final analysis at day +100 after allogeneic stem cell transplantation
infection incidence
Measured: 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
Measured: every 6 months for safety and in the final analysis at day +30 after allogeneic stem cell transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2010 (estimated)
- Study startMay 2004
- Primary completionJan 2015
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 129 participants (actual)
Sponsor and investigators
- Lead sponsor
- European Society for Blood and Marrow Transplantation
- Sponsor type
- Research network
- Collaborators
- Pierre Fabre Medicament
- Responsible party
- Sponsor
- Investigators
- Nicolaus Kröger, MD, Study chair, Universitätsklinikum Hamburg-EppendorfAxel R Zander, MD, Principal investigator, University Hospital Hamburg-Eppendorf, GermanyGhulam J Mufti, MD, Principal investigator, King's College Hospital London, United KingdomMarie Robin, MD, Principal investigator, Hopital Saint-Louis Paris, FranceKathrin Haifa Al-Ali, MD, Principal investigator, University Hospital Leipzig, GermanyDietger Niederwieser, MD, Principal investigator, University Hospital Leipzig, GermanyGiorgio Lambertenghi Deliliers, Principal investigator, IRCCS Ospedale Maggiore of Milan, ItalyDomink Heim, Prof., Principal investigator, University Hospital, Basel, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01203228
- Sponsor's protocol ID
- 2005-002011-24
- Other IDs
- EBMT 42205525, 2005
- Acronym
- RICMAC
- Status last verified
- Apr 2015
- First submitted
- 15 Sep 2010
- Last updated
- 3 Apr 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01203228
- Acronym / sponsor ID
- RICMAC / 2005-002011-24
- Keywords
- Reduced Intensity conditioning, Myeloablative conditionig, Allogeneic stem cell transplantation, MUD
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 129 participants (actual)
- Lead sponsor
- European Society for Blood and Marrow TransplantationResearch network
- Collaborators
- Pierre Fabre Medicament
- Study start
- May 2004
- Primary completion
- Jan 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 16 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Other: Myeloablative conditioningMyeloablative conditioning |
| B | Experimental | Other: Reduced Intensity ConditioningReduced Intensity Conditioning |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Disease: Cytologically proven primary or therapy-related myelodysplastic syndrome (MDS), either as
- 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):
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Reduced Intensity ConditioningAlso: Myleran, Sulphabutin, Busulphan, LeucosulfanBusilvex®: 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 | B |
| Myeloablative conditioningAlso: Myleran, Sulphabutin, Busulphan, LeucosulfanBusilvex®: 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 | A |
Primary outcome
non-relapse mortality
Time frame: every 6 months for safety and in the final analysis at one year after allogeneic stem cell transplantation
9 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
Haematopoeitic recovery
Time frame: every 6 months for safety and in the final analysis at day +30 after allogeneic stem cell transplantation
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2015.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicolaus Kröger, MD study chair
Universitätsklinikum Hamburg-Eppendorf
Axel R Zander, MD principal investigator
University Hospital Hamburg-Eppendorf, Germany
Ghulam J Mufti, MD principal investigator
King's College Hospital London, United Kingdom
14 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Reduced Intensity Conditioning and Myeloablative conditioning in people with Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia, run by European Society for Blood and Marrow Transplantation at 14 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Germany, Italy, Netherlands, Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
non-relapse mortality (time frame: every 6 months for safety and in the final analysis at one year after allogeneic stem cell transplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2015.