Primary objective of this open label, two-arm, multicenter, multinational, randomized trial is to compare anit-leukemic activity of allogeneic stem cell transplantation for patients with acute leukemia in complete remission between a 10/10 HLA…
ID
Source
Brief title
Condition
- Leukaemias
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Relapse incidence at two years between both arms.
Secondary outcome
- Overall survival at two years between both arms
- Overall survival for all patients assigned to one of the two treatment arms
as time to event endpoint
- Comparison of GVHD/relapse-free survival as composite endpoint in both arms
- Comparison of non-relapsed mortality (NRM) at 1 and 2 years after allogeneic
SCT in both arms
- Comparison of acute graft-versus-host disease (aGVHD) on day +100 and 1 year
(max grade) after allogeneic SCT between both arms
- Comparison of chronic graft-versus-host disease (cGVHD) at 1 and 2 years
after allogeneic SCT between both arms
- Comparison of toxicity of both regimens between both arms
- Comparison of immune reconstitution and full donor chimerism between both
arms
- Evaluation of Sorror Risk Score on outcome after allogeneic SCT
- Comparison of QOL (FACT-BMT) before and after transplantation at day +100, 6
m, 1 year,2 years between both arms
Background summary
Allogeneic stem cell transplant for acute myeloid leukemia and high risk MDS
from a matched unrelated donor (10/10 HLA) has been regarded as the best
alternative donor option if no HLA-identical sibling is available. The use of
post-transplant cyclophosphamide as GVHD prophylaxis has increased the number
of haploidentical donor cell transplantations worldwide, and retrospective
studies suggest similar outcome and a trend for lower relapse if myeloablative
conditioning is used. If the outcome of haploidentical stem cell
transplantation is improved by a lower rate of relapse, this will have major
input in the field of stem cell transplantation resulting in a faster donor
availability and in cost reduction of the stem cell procedure. Thus, it is
important to perform a randomized prospective trial with identical conditioning
regimen and identical GVHD prophylaxis with post-transplantation
cyclophosphamide
Hypothesis: haploidentical stem cell transplantation with post cyclophosphamide
induces a stronger anti-leukemic activity in comparison to 10/10 HLA matched
unrelated donor and reduces the risk of relapse at 2 years after stem cell
transplantation by 10%.
Study objective
Primary objective of this open label, two-arm, multicenter, multinational,
randomized trial is to compare anit-leukemic activity of allogeneic stem cell
transplantation for patients with acute leukemia in complete remission between
a 10/10 HLA matched unrelated donor and a haploidentical donor.
Secondary objectives are to assess and compare the safety and efficacy of study
treatments therapy in both study arms on non-relapse mortality (NRM),
relapse-free survival (RFS), overal survival (OS), QOL, toxicity, development
of acute and chronic GvHD as well as engraftment and chimerism and impact of
measurable residual disease.
Study design
Open label, two-arm, mulicenter, multinational, randomized phase II trial.
Treatment arm A is allogeneic stem cell transplantation form 10/10 HLA matched
unrelated donor. Treatment arm B is allogeneic stem cell transplantation from
haploidentical donor.
Intervention
Allogeneic stem cell transplantation with PBSC as stem cell source from the
matched unrelated donor or haploindentical donor.
The conditioning regime in both arms is the same, but based on patients age:
<= 50 years: Busulfan (16 mg/kgBW orally or 12.8 mg/kgBW i.v.) / fludarabine
(160 mg/m2) or TBI (12 - 13.2 Gy) / fludarabine (160 mg/m2)
> 50 years (or Sorror score >= 3): Busulfan (12 mg/kgBW orally or 9.6 mg/kgBW
i.v.) / fludarabine (160 mg/m2) or TBI (8 Gy) / fludarabine (160 mg/m2)
The Graft versus Host Disease prophylaxe is the same in both arms:
Cyclophosphamide 50 mg/kg on day +3 and +4
Tacrolimus from day +5 until day +120
MMF from day +5 until day +35
Study burden and risks
the risk associated with paritcipation is the same as the regular risks of
undergoing an allogeneic stemcell transplantation.
Martinistrasse 32
Hamburg D-20246
DE
Martinistrasse 32
Hamburg D-20246
DE
Listed location countries
Age
Inclusion criteria
- AML intermediate or high risk according to ELN or ALL high risk according to
ESMO guidelines in 1. CR or AML/ALL in 2. CR, or high risk MDS (according to
IPSS-R) in 1. CR or 2. CR.
- Patients age 18 - 70 years.
- Signed informed consent form
- ECOG <= 2
- 10/10 HLA-matched unrelated donor and haploidentical (>= 5/10 and <= 8/10 HLA)
relative
matched donor
Exclusion criteria
- Severe renal, hepatic, pulmonary or cardiac disease,
- Positive serology for HIV
- Pregnant or lactating women
- Uncontrolled invasive fungal infection at time of screening (baseline)
- Serious psychiatric or psychological disorders
- Uncontrolled severe autoimmune disease or uncontrolled other malignancy
- Availability of an HLA-identical sibling as donor source
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT04232241 |
| CCMO | NL72936.000.21 |