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

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

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.

Study Overview

• Status: Unknown
• Conditions: Hematologic Diseases
• Intervention / Treatment: Drug: Everolimus and mycophenolate sodium

• Study Type: Interventional
• Enrollment (Anticipated): 38
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Reinhard Marks, MD; Phone Number: 3278 49-761-270-; Email: reinhard.marks@uniklinik-freiburg.de
• Study Contact Backup: Name: Juergen Finke, MD; Phone Number: 3408 49-761-270-; Email: juergen.finke@uniklinik-freiburg.de

Study Locations

• Germany
  • Baden-Wuerttemberg
    • Freiburg, Baden-Wuerttemberg, Germany, 79104
      • Recruiting
      • University Medical Center, Division Hematology/Oncology
      • Contact: Reinhard Marks, MD; Phone Number: 3278 49-761-270; Email: reinhard.marks@uniklinik-freiburg.de
      • Sub-Investigator: Reinhard Marks, MD
      • Principal Investigator: Juergen Finke, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Everolimus and mycophenolate sodium; Combination of experimental immunosuppressants for GvHD prophylaxis	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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University Hospital Freiburg
• Investigators: Principal Investigator: Juergen Finke, MD, University Medical Center Freiburg, Div. Hematology/Oncology; Study Director: Reinhard Marks, MD, University Medical Center Freiburg, Div. Hematology/Oncology

Publications and helpful links

General Publications

• Schäfer H, Blümel-Lehmann J, Ihorst G, Bertz H, Wäsch 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Anticipated): March 1, 2010
• Study Completion (Anticipated): March 1, 2011

Study Registration Dates

• First Submitted: March 4, 2009
• First Submitted That Met QC Criteria: March 4, 2009
• First Posted (Estimate): March 5, 2009

Study Record Updates

• Last Update Posted (Estimate): March 5, 2009
• Last Update Submitted That Met QC Criteria: March 4, 2009
• Last Verified: March 1, 2009

More Information

Terms related to this study

• Keywords: Immunosuppression; Drug Therapy, Combination; Hematopoietic Stem Cell Transplantation
• Additional Relevant MeSH Terms: Hematologic Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid; Everolimus
• Other Study ID Numbers: 00557