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

Primary Purpose

Myelodysplastic Syndromes, Secondary Acute Myeloid Leukemia

Status

Terminated

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Reduced Intensity Conditioning

Myeloablative conditioning

About this trial

This is an interventional treatment trial for Myelodysplastic Syndromes focused on measuring Reduced Intensity conditioning, Myeloablative conditionig, Allogeneic stem cell transplantation, MUD

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm Description

Myeloablative conditioning

Reduced Intensity Conditioning

Outcomes

Primary Outcome Measures

non-relapse mortality

Secondary Outcome Measures

organ related toxicity of conditioning

Incidence of aGVHD

incidence of cGVHD

overall survival

event-free survival

cumulative incidence of relapse

VOD

infection incidence

Haematopoeitic recovery

Full Information

NCT ID

NCT01203228

First Posted

September 15, 2010

Last Updated

April 2, 2015

Sponsor

European Society for Blood and Marrow Transplantation

Collaborators

Pierre Fabre Medicament

1. Study Identification

Unique Protocol Identification Number

NCT01203228

Brief Title

Dose-reduced Versus Standard Conditioning in MDS/sAML

Acronym

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)

Study Type

Interventional

2. Study Status

Record Verification Date

April 2015

Overall Recruitment Status

Terminated

Study Start Date

May 2004 (undefined)

Primary Completion Date

January 2015 (Actual)

Study Completion Date

February 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

European Society for Blood and Marrow Transplantation

Collaborators

Pierre Fabre Medicament

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Myelodysplastic Syndromes, Secondary Acute Myeloid Leukemia

Keywords

Reduced Intensity conditioning, Myeloablative conditionig, Allogeneic stem cell transplantation, MUD

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

129 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Active Comparator

Arm Description

Myeloablative conditioning

Arm Title

Arm Type

Experimental

Arm Description

Reduced Intensity Conditioning

Intervention Type

Other

Intervention Name(s)

Reduced Intensity Conditioning

Other Intervention Name(s)

Myleran, Sulphabutin, Busulphan, Leucosulfan, Myeloleukon, Citosulfan, Mielevcin, Milecitan, Fludara, Beneflur, Fludura, FAMP, 2-Fluoro-ara-AMP

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

Myeloablative conditioning

Other Intervention Name(s)

Myleran, Sulphabutin, Busulphan, Leucosulfan, Myeloleukon, Citosulfan, Mielevcin, Milecitan, cyclophosphamide, Procytox, Cytoxan, Cyclophosphan, Cytophosphan, Claphene, Cyclostin, Endoxan

Intervention Description

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

Primary Outcome Measure Information:

Title

non-relapse mortality

Time Frame

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

Secondary Outcome Measure Information:

Title

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

Title

Incidence of aGVHD

Time Frame

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

Title

incidence of cGVHD

Time Frame

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

Title

overall survival

Time Frame

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

Title

event-free survival

Time Frame

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

Title

cumulative incidence of relapse

Time Frame

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

Title

VOD

Time Frame

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

Title

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

Title

Haematopoeitic recovery

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials: