Objectives: - to increase the proportion of patients with non-severe GVHD within 180 days post-allo-SCT - to reduce the progression rate - to improve the progression free survival- to asses the impact on the quality of life using a time restricted…
ID
Source
Brief title
Condition
- Haematological disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Proportion of patients with non-severe GVHD (acute GVHD grade I, grade II
without gut infiltration, or chronic GVHD not requiring systemic treatment)
within D180 after randomization / registration.
Secondary outcome
- time to acute GVHD grade I, II, III, IV
- cumulative incidence of progression
- progression-free survival (defined as time from randomization 1 until
progression or death, whichever occurs first)
- cumulative incidence of non-relapse mortality
- overall survival
- time to chronic GVHD limited and extensive
- adverse events
- Quality of life (of randomized patients) as defined by the EORTC QLQ-C30 and
the FACT-BMT definitions
Background summary
Allogeneic hematopoietic stem cell transplantation (SCT) has been established
as the powerful treatment modality for patients with acute leukemia.
Especially, the immunotherapeutic effect, known as the graft versus leukemia
effect, significantly reduces the rate of relapse in leukemic patients,
receiving their allograft as consolidation therapy in first or subsequent
remission. In addition, the graft versus tumor effect can also be observed in
patients with malignant lymphoma or multiple myeloma. That immunotherapeutic
effect is strongly associated with the occurrence of acute and/or chronic graft
versus host disease (GVHD). However, patients with severe acute grade III-IV or
chronic extensive GVHD may experience excess mortality and thereby severe GVHD
remains the most important complication of allogeneic SCT. Currently, different
immunosuppressive regimens are used in order to prevent GVHD. The optimal
duration of GVHD prevention is, however, not known and a subject of continuing
debate. In the current study 3 regimens will be compared: a prolonged
immunosuppressive regimen, a time-restricted regimen and a short-course GVHD
prophylaxis consisting of post-transplant cyclophosphamide. The aim of the
study is to make optimal use of the immunotherapeutic effect of the allo-SCT by
increasing the number of patients with non-severe GVHD, without compromising
this by a substantial increase of serious GVHD.
Study objective
Objectives:
- to increase the proportion of patients with non-severe GVHD within 180 days
post-allo-SCT
- to reduce the progression rate
- to improve the progression free survival
- to asses the impact on the quality of life
using a time restricted immunosuppressive regimen or a short-course
post-transplant GVHD prophylaxis consisting of high-dose cyclophosphamide as
compared to a prolonged, standard immunosuppressive regimen
Additional objectives:
- to develop a predictive score, by means of clinical and laboratory parameters
(using genomic and proteomic approaches) that allows for accurate
identification of patients at high risk of severe GVHD as well as for
identification of patients, who will not develop GVHD
Study design
A phase III randomized trial.
Intervention
Prevention of GvHD
3 regimens will be compared: a time-restricted immunosuppressive regimen
(Myfortic for 28 days and Cyclosporine A for 84 days), a prolonged regimen
(Myfortic for 84 days and Cyclosporine A for 180 days) and a short-course
post-transplant GVHD prophylaxis consisting of high-dose cyclophosphamide
Study burden and risks
The extra burden associated with participation is
- once an extra bloodsample (during regular bloodsamping) of 48 ml
- filling out 5 Qol questionnaires.
Since patients are already very thorougly followed after allo SCT, the extra
burden associated with particpation in this trial is limited.
On theoretical grounds there could occur more severe GVHD in a time-restricted
immunosuppressive regimen. However, from previous experience the chance of this
happening is small. This study is deemed justified from the fact that a
time-restricted immunosuprresive regimen can accomplish a lower relapse rate.
The main risk of arm 3 is increased mucosal toxicity and a prolonged duration
of admission. However, if in the setting of arm 1 or 2 the patient will be
treated with a myeloablative conditioning regimen, mucosal toxicity will be
worse compared to arm 3. World-wide experience with arm 3 has shown no other
specific risks. Compared to arm 1 and 2 , the chance to develop severe GvHD or
fatal infections might be less.
HOVON Centraal Bureau, VUmc, De Boelelaan 1117
Amsterdam 1081 HV
NL
HOVON Centraal Bureau, VUmc, De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
-Age 18-70 inclusive
-AML, MDS, ALL, MM, CML, CLL, NHL, HL, or a myeloproliferative disease (MPD)
-Planned allogeneic stem cell transplantation
-Related or unrelated donor with a 8/8 HLA match (HLA A, B, C, DRB1)
-WHO performance status 0-2
-Written Informed Consent
-Negative pregnancy test (if applicable)
-Patients who are willing and capable to use adequate contraception during
Myfortic treatment (all pre-menopausal women)
Exclusion criteria
- Renal dysfunction (serum creatinine > 150 mmol/L or clearance < 50 ml/min)
- Patients with active, uncontrolled infection
- Cord Blood transplantation
- Patients receiving ATG pre-transplantation as part of the conditioning regimen
- Patients with progressive disease in case of MM, CLL, NHL, HL
- Patients with > 5% marrow blasts in case of AML, ALL, CML
- Patients with EMD in case of AML, ALL, CML
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2008-003540-11-NL |
| CCMO | NL27061.078.09 |