Clinical Trial Results:
A Randomized Phase III study comparing conventional chemotherapy to low dose total body irradiation-based conditioning and hematopoietic cell transplantation from related and unrelated donors as consolidation therapy for older Patients with AML in first Complete Remission.

Trial information Top of page
Trial identification
Sponsor protocol code	HCTvs.CTelderlyAML
Additional study identifiers
ISRCTN number	-
US NCT number	NCT00766779
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	The European Society for Blood and Marrow Transplantation
Sponsor organisation address	Rijnsburgerweg 10, Leiden, Netherlands, 2333 AA
Public contact	hctvsct@zks.uni-leipzig.de, Leipzig University, hctvsct@zks.uni-leipzig.de
Scientific contact	hctvsct@zks.uni-leipzig.de, Leipzig University, hctvsct@zks.uni-leipzig.de
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	25 Aug 2021
Is this the analysis of the primary completion data?	Yes
Primary completion date	31 Aug 2020
Global end of trial reached?	Yes
Global end of trial date	31 Aug 2020
Was the trial ended prematurely?	Yes
General information about the trial
Main objective of the trial	To evaluate LFS after allogeneic HCT in AML/RAEB in CR using matched or unrelated donors in comparison to conventional chemotherapy Primary endpoints - Leukemia free survival (LFS)
Protection of trial subjects	An independent data monitoring committee was installed.
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	11 Jan 2010
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	Yes
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Netherlands: 33
Country: Number of subjects enrolled	Germany: 79
Country: Number of subjects enrolled	Switzerland: 13
Worldwide total number of subjects	125
EEA total number of subjects	112
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	37
From 65 to 84 years	88
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	245 Patients were recruited registered for the trial from 11.01.2011 until 31.08.2017 in the participating trial sites in Germany, the Netherlands, France, Switzerland, Austria and Australia.
Pre-assignment
Screening details	A total of 125 patients proceeded to randomisation.
Period 1
Period 1 title	overall trial (overall period)
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Not blinded
Arms
Are arms mutually exclusive	Yes
Arm title	stem cell transplant
Arm description	hematopoietic stem cell transplantation after low dose total body irradiation-based conditioning
Arm type	Experimental
Investigational medicinal product name	Fludarabine
Investigational medicinal product code
Other name
Pharmaceutical forms	Powder for infusion
Routes of administration	Intravenous use
Dosage and administration details	Per day: 30 mg/m2 mg/m2, days -4, -3, -2
Investigational medicinal product name	Ciclosporin
Investigational medicinal product code
Other name
Pharmaceutical forms	Concentrate for concentrate for solution for infusion, Capsule, soft + tablet
Routes of administration	Intravenous use, Oral use
Dosage and administration details	Start day -3 until day 84, then taper
Investigational medicinal product name	Mycophenolatmofetil
Investigational medicinal product code
Other name
Pharmaceutical forms	Powder for concentrate for solution for injection/infusion, Capsule
Routes of administration	Oral use, Intravenous use
Dosage and administration details	Per day: 45 mg/kg mg/kg, related donor: day 0 until day 28, unrelated donor: day 0 until day 28, then reduction of 500mg / 14 days
Investigational medicinal product name	hematopoietic stem cells
Investigational medicinal product code
Other name
Pharmaceutical forms	Infusion
Routes of administration	Intravenous use
Dosage and administration details	The peripheral blood stem cell (PBSC) graft should contain at least 4 x 106 /kg CD34 and 3 x 108 /kg CD3+ cells. Infusion on day 0.
Arm title	non stem cell transplant
Arm description	Patients randomized in Arm B were scheduled to receive further consolidation according to an upfront specified trial site protocol.
Arm type	standard of care
Investigational medicinal product name	Mitoxantron
Investigational medicinal product code
Other name
Pharmaceutical forms	Concentrate for solution for infusion
Routes of administration	Intravenous use
Dosage and administration details	Per day: 10 mg/m2, days 1 and 2
Investigational medicinal product name	Cytarabin
Investigational medicinal product code
Other name
Pharmaceutical forms	Solution for injection/infusion
Routes of administration	Intravenous use
Dosage and administration details	Per day: 500 mg/m2, days 1, 3 and 5
Number of subjects in period 1 stem cell transplant non stem cell transplant Started 83 42 Completed 66 35 Not completed 17 7      Relapse 2 2      miscellaneous reasons 5 -      donor not available 3 -      Withdrawal 3 3      Morbidity 4 2

Subject disposition Top of page

Baseline characteristics Top of page

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	stem cell transplant
Reporting group description	hematopoietic stem cell transplantation after low dose total body irradiation-based conditioning
Reporting group title	non stem cell transplant
Reporting group description	Patients randomized in Arm B were scheduled to receive further consolidation according to an upfront specified trial site protocol.

End points Top of page

Primary: Leukaemia free survival (LFS) Top of page
End point title	Leukaemia free survival (LFS) [1]
End point description
End point type	Primary
End point timeframe	5 years
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The trial was stopped prematurely. For further description see the attached trial synopsis.
End point values stem cell transplant non stem cell transplant Number of subjects analysed 83 42 Units: whole 83 42
No statistical analyses for this end point

Primary: Leukaemia free survival (LFS) Top of page

Adverse events Top of page
Adverse events information [1]
Timeframe for reporting adverse events	Before Amendment 1 adverse events were reported from between the first study-related procedure (i.e. screening) until 30 days post the last study treatment. After Amendment 1 the reporting period changed to day 0 (start of trial therapy) until day 100.
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	24.1
Reporting groups
Reporting group title	stem cell transplant
Reporting group description	-
Reporting group title	non stem cell transplant
Reporting group description	-
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Please see the list of AEs related and not related to the IMP in the trial synopsis, uploaded together with the posting of this results report.
Serious adverse events stem cell transplant non stem cell transplant Total subjects affected by serious adverse events      subjects affected / exposed 7 / 66 (10.61%) 1 / 35 (2.86%)      number of deaths (all causes) 4 0      number of deaths resulting from adverse events Vascular disorders Circulatory collapse      subjects affected / exposed 1 / 66 (1.52%) 0 / 35 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Haemorrhage neonatal      subjects affected / exposed 1 / 66 (1.52%) 0 / 35 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 1 0 / 0 Blood and lymphatic system disorders Splenic haemorrhage      subjects affected / exposed 1 / 66 (1.52%) 0 / 35 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 1 0 / 0 General disorders and administration site conditions Death      subjects affected / exposed 1 / 66 (1.52%) 0 / 35 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 1 0 / 0 Gastrointestinal disorders Gastrointestinal haemorrhage      subjects affected / exposed 1 / 66 (1.52%) 0 / 35 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Renal and urinary disorders Acute kidney injury      subjects affected / exposed 1 / 66 (1.52%) 0 / 35 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Renal failure      subjects affected / exposed 0 / 66 (0.00%) 1 / 35 (2.86%)      occurrences causally related to treatment / all 0 / 0 1 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Infections and infestations Human herpesvirus 6 infection      subjects affected / exposed 1 / 66 (1.52%) 0 / 35 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Pneumonia      subjects affected / exposed 1 / 66 (1.52%) 0 / 35 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0      deaths causally related to treatment / all 1 / 1 0 / 0
Frequency threshold for reporting non-serious adverse events: 5%
Non-serious adverse events stem cell transplant non stem cell transplant Total subjects affected by non serious adverse events      subjects affected / exposed 0 / 66 (0.00%) 0 / 35 (0.00%)

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? Yes
Date	Amendment
04 Nov 2011	Complete Revision
03 Jul 2013	Amendment
07 Nov 2013	Amendment
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
None reported

More information Top of page