Safety Study of Calcineurin Inhibitor Free GvHD Prophylaxis in Allogeneic Stem Cell Transplantation

Study Overview
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Brief Summary
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In stem cell transplantation as treatment for malignant diseases, calcineurin inhibitors like cyclosporine A are commonly used to prevent tissue destruction (GvHD) by activated donor immune cells. The hypothesis for this study is, that replacing calcineurin inhibitors by everolimus and mycophenolate as GvHD prophylaxis not only reduces toxicity of the treatment but also improves tolerance induction of the donor T cells toward the host, eventually increasing the safety of stem cell transplantation.

Official Title
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Everolimus and Mycophenolate Sodium as GvHD Prophylaxis in Allogeneic Stem Cell Transplantation

Conditions
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Hematologic Diseases

Intervention / Treatment
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* Drug: Everolimus and mycophenolate sodium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of hematologic malignancies, indicated for allogeneic stem cell transplantation: acute myeloid leukemia (AML), in CR1, ≥ CR2, primary refractory, relapse chronic myeloid leukemia (CML), in chronic phase, in acceleration or blast crisis myelodysplastic syndrome (MDS), RA/RARS (transfusion dependent), RAEB, RAEB-t and CMML Lymphoma: plasmocytoma immunocytoma (M. Waldenström) chronic-lymphatic leukemia (CLL) additional low and high grade Non-Hodgkin Lymphoma Hodgkins disease HLA-matched (HLA-A, -B, -DRB1) related or unrelated donor available Signed informed consent Exclusion Criteria: CNS involvement by underlying disease Pulmonary disease with VC < 55%, DLCO < 40% Cardiac ejection fraction < 30%, uncontrollable arrhythmia Creatinin > 1,5 mg/dl or Creatinin-Clearance < 30 ml/min Bilirubin > 2 mg/dl Active Hepatitis B or C HIV serologic positive Pregnancy and lactation Pre-menstrual women without medical safe contraception Participation on another clinical trial in between 30 days before start or during the study only if the clinical trial interferes with the outcome measures. Known allergy to study medication or ingredients of the formulation Drug- or alcohol abuse Non-compliance

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Everolimus and mycophenolate sodium<br>Combination of experimental immunosuppressants for GvHD prophylaxis | Drug: Everolimus and mycophenolate sodium<br>* Everolimus tablets, 1.5mg/day bid, dosage adjusted to plasma levels Mycophenolate sodium, 720mg/day bid Duration: Mycophenolate tapering starts at day 56 after stem cell transplantation Everolimus tapering starts at day 100 after stem cell transplantation if no GvHD evident<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity according to CTCAE v3.0 |  | after 100 days and one year after treatment start | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematopoietic engraftment |  | day 30 after stem cell transplantation | 
| Incidence of acute and chronic GvHD |  | one year after stem cell transplantation | 
| Progression free survival |  | Day 100 and one year after stem cell transplantation | 
| Overall survival |  | day 100 and one year after stem cell transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hematopoietic Stem Cell Transplantation, Drug Therapy, Combination, Immunosuppression