Multicenter Study of Peritransplantation Immunosuppression for Mismatched Hematopoietic Cell Transplantation After Reduced Intensity Conditioning

Multicenter Phase II Study of Peritransplantation Immunosuppression Using ATG, Rituximab, Sirolimus and Mycophenolate Mofetil in Patient Receiving Mismatched Hematopoietic Cell Transplantation After Reduced Intensity Conditioning With Fludarabine and Treosulfan

Feasibility and toxicity of peritransplantation immunosuppression with ATG, sirolimus, mycophenolate mofetil and rituximab in patients receiving mismatched allogeneic HCT after a reduced intensity conditioning regimen with fludarabine/treosulfan

Study Overview

• Status: Terminated
• Conditions: Patients Receiving Mismatched Allogeneic HCT
• Intervention / Treatment: Drug: immunosuppression

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Mainz, Germany, D-55101
    • Hematology/Oncology Medical Center University Hospital of Mainz
  • Nuernberg, Germany, D-90419
    • Bone Marrow Transplantation Unit Medical Center University Hospital of Nuernberg
  • Tuebingen, Germany, D-72076
    • Department of Hematology/Oncology Medical Center University Hospital of Tuebingen
  • Wiesbaden, Germany, D-65191
    • BMT-Unit Deutsche Klinik für Diagnostik

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients scheduled for mismatched allogeneic HCT
• Unrelated donor with maximal 2 antigen or allelic mismatches in HLA-I or HLA-II
• Age >=75, >=18 years
• Patients Age <=50 if a HCT-CI score > 2 [acc. to Sorror et al., 2005]
• Karnofsky Index >60%

• Patients with:

  • Acute myeloid leukemia in CR (<5% blasts)
  • Acute lymphoblastic leukemia in CR (< 5% blasts)
  • Myelodysplastic syndrome with up to 20% blasts
  • Osteomyelofibrosis
  • Chronic lymphocytic leukemia
  • High grade Non-Hodgkin Lymphoma in CR or PR
  • Low grad Non-Hodgkin Lymphoma in CR or PR
  • M. Hodgkin in CR or PR
  • Chronic myeloid leukaemia in chronic phase or CR of blast crisis

Exclusion Criteria:

• Patients with >5% blasts in BM at the time of transplantation
• Progressive or chemorefractory disease
• Less than 3 months after preceding HCT
• CNS involvement with disease
• Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month.
• Liver function abnormalities with bilirubin >2 mg/dL and elevation of transaminases higher 2x upper limit of normal.
• Chronic active viral hepatitis
• Ejection fraction <40 % on echocardiography
• Patients with > grade II hypertension by CTC criteria
• Creatinine clearance <50 ml/min
• Proteinuria >800 mg/24 h
• Respiratory failure necessitating supplemental oxygen or DLCO <30%
• Allergy against murine antibodies
• Known allergy/intolerance against sirolimus or one of it's excipients
• HIV-Infection
• Female patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control during study treatment and for at least 12 months thereafter. (Women of childbearing potential must have a negative serum pregnancy test at study entry)
• Concurrent severe and/or uncontrolled medical disease (e.g. uncontrolled diabetes, congestive heart failure, myocardial infarction within 6 months prior to the study, unstable and uncontrolled hypertension, chronic renal disease, or active uncontrolled infection) which could compromise participation in the study
• Patients with a history of psychiatric illness or condition which could interfere with their ability to understand the requirements of the study (this includes alcoholism/drug addiction)
• Patients unwilling or unable to comply with the protocol
• Unable to give informed consent
• Enrollment in an other trial interfering with the endpoints of this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Treatment related mortality	12 months after HCT
Treatment related mortality	24 months after HCT

Secondary Outcome Measures

Outcome Measure	Time Frame
Toxicity according CTC of protocol on day 100	on day 100
Engraftment on day 100	on day 100
Overall survival	12 months after HCT
Incidence of graft versus host disease	3 months after HCT
Incidence of infections	2 years after HCT
Immune reconstitution of CD3, CD3/CD4/CD8, CD56, CD19 cells	3 months after HCT
Overall survival	24 months after HCT
Incidence of graft versus host disease	6 months after HCT
Disease free survival	24 months after HCT
Disease response	12 months after HCT
Disease response	24 months after HCT
Immune reconstitution of CD3, CD3/CD4/CD8, CD56, CD19 cells	6 months after HCT
Immune reconstitution of CD3, CD3/CD4/CD8, CD56, CD19 cells	12 months after HCT
Immune reconstitution of CD3, CD3/CD4/CD8, CD56, CD19 cells	24 months after HCT
Incidence of graft versus host disease	12 months after HCT
Incidence of graft versus host disease	24 months after HCT

Collaborators and Investigators

• Sponsor: Prof. Dr. med. Wolfgang Bethge
• Collaborators: Pfizer; medac GmbH; Neovii Biotech
• Investigators: Principal Investigator: Wolfgang A Bethge, MD, Medical Center University Hospital of Tuebingen

Publications and helpful links

Helpful Links

• Results

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (ACTUAL): August 17, 2016
• Study Completion (ACTUAL): August 17, 2016

Study Registration Dates

• First Submitted: April 16, 2012
• First Submitted That Met QC Criteria: April 19, 2012
• First Posted (ESTIMATE): April 20, 2012

Study Record Updates

• Last Update Posted (ACTUAL): July 5, 2022
• Last Update Submitted That Met QC Criteria: June 29, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: E:531/2011; 2011-002192-41 (EUDRACT_NUMBER)