Clinical trial NCT00856505: Safety Study of Calcineurin Inhibitor Free GvHD Prophylaxis in Allogeneic Stem Cell Transplantation
Official title: Everolimus and Mycophenolate Sodium as GvHD Prophylaxis in Allogeneic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Hematologic Diseases
Keywords: Hematopoietic Stem Cell Transplantation
Drug Therapy, Combination
Immunosuppression
Lead sponsor: University Hospital Freiburg
Sponsor class: OTHER
First posted: 2009-03-05
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Toxicity according to CTCAE v3.0
timeFrame: after 100 days and one year after treatment start
Secondary outcomes:
measure: Hematopoietic engraftment
timeFrame: day 30 after stem cell transplantation
measure: Incidence of acute and chronic GvHD
timeFrame: one year after stem cell transplantation
measure: Progression free survival
timeFrame: Day 100 and one year after stem cell transplantation
measure: Overall survival
timeFrame: day 100 and one year after stem cell transplantation
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: University Medical Center, Division Hematology/Oncology
state: Baden-Wuerttemberg
Study officials:
affiliation: University Medical Center Freiburg, Div. Hematology/Oncology
name: Juergen Finke, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center Freiburg, Div. Hematology/Oncology
name: Reinhard Marks, MD
role: STUDY_DIRECTOR
References:
citation: Schafer H, Blumel-Lehmann J, Ihorst G, Bertz H, Wasch R, Zeiser R, Finke J, Marks R. A prospective single-center study on CNI-free GVHD prophylaxis with everolimus plus mycophenolate mofetil in allogeneic HCT. Ann Hematol. 2021 Aug;100(8):2095-2103. doi: 10.1007/s00277-021-04487-y. Epub 2021 Mar 23.