Prevention of severe GVHD after allogeneic hematopoietic stem cell transplantation, applied as consolidation immunotherapy in patients with hematological malignancies. A prospective randomized phase III trial.

Study phase:

Phase III.



Objectives R1:

1. To reduce the proportion of patients without GVHD within 180 days post-allo-SCT;

2. To reduce the progression rate;

3. To improve the progression free survival;

4. To asses the impact on the quality of life
using a time restricted immunosuppressive regimen as compared to a prolonged, standard immunosuppressive regimen.



Additional objectives:

1. 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.



Patient population:

All patients planned to undergo an allogeneic SCT for malignant hematological disorders and with a related or unrelated 8/8 HLA matched donor are eligible for randomization 1. No ATG will be given pre-transplantation as part of the conditioning regimen.



Study design:

Prospective, multicenter, open-label randomized.



Duration of treatment:

The expected duration of full dose immunosuppressive treatment after randomization 1 will be 84 to 180 days.

Randomization 1:

The hypothesis to be tested is that the outcome in arm B is better than in arm A.

Clinical and laboratory evaluations:



Randomization 1:

1. At entry (before start of conditioning);

2. At day 0, 14 and 28;

3. Thereafter monthly during first year after allo-SCT;

4. Every 6 months from 1-5 yr after allo-SCT.



Quality of life:

1. At entry, i.e. at admission prior to the initiation of the conditioning regimen;

2. At 180 days after allo-SCT;

3. At 1 year after allo-SCT;

4. At 2 years after allo-SCT;

5. At 5 years after allo-SCT.

The quality of life measurements will be stopped at progression.

Patients planned to undergo an allogeneic SCT for malignant hematological disorders and with a related or unrelated 8/8 HLA matched donor will be randomized to either standard immunosuppression (arm 1) or time restricted immunosuppression (arm 2). No ATG will be given pretransplantation as part of the conditioning regimen.