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

Hematologic Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00856505
• Other study ID #: 00557
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: March 4, 2009
• Last updated: March 4, 2009
• Start date: March 2008
• Est. completion date: March 2011

Study information

• Verified date: March 2009
• Source: University Hospital Freiburg
• Contact: Reinhard Marks, MD
• Phone: 49-761-270-
• Email: reinhard.marks[@]uniklinik-freiburg.de
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 38
• Est. completion date: March 2011
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hematologic Diseases

Intervention

Drug:
• Everolimus and mycophenolate sodium
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

Locations

Country	Name	City	State
Germany	University Medical Center, Division Hematology/Oncology	Freiburg	Baden-Wuerttemberg

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Freiburg

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity according to CTCAE v3.0		after 100 days and one year after treatment start	Yes
Secondary	Hematopoietic engraftment		day 30 after stem cell transplantation	Yes
Secondary	Incidence of acute and chronic GvHD		one year after stem cell transplantation	Yes
Secondary	Progression free survival		Day 100 and one year after stem cell transplantation	No
Secondary	Overall survival		day 100 and one year after stem cell transplantation	Yes