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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University Hospital Tuebingen
Sponsor:
Collaborators:
medac GmbH
Pfizer
Neovii Biotech
Information provided by (Responsible Party):
Prof. Dr. med. Wolfgang Bethge, University Hospital Tuebingen
ClinicalTrials.gov Identifier:
NCT01582048
First received: April 16, 2012
Last updated: May 28, 2014
Last verified: May 2014
  Purpose

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


Condition Intervention Phase
Patients Receiving Mismatched Allogeneic HCT
Drug: immunosuppression
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University Hospital Tuebingen:

Primary Outcome Measures:
  • Treatment related mortality [ Time Frame: 12 months after HCT ] [ Designated as safety issue: Yes ]
  • Treatment related mortality [ Time Frame: 24 months after HCT ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Toxicity according CTC of protocol on day 100 [ Time Frame: on day 100 ] [ Designated as safety issue: Yes ]
  • Engraftment on day 100 [ Time Frame: on day 100 ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: 12 months after HCT ] [ Designated as safety issue: Yes ]
  • Incidence of graft versus host disease [ Time Frame: 3 months after HCT ] [ Designated as safety issue: Yes ]
  • Incidence of infections [ Time Frame: 2 years after HCT ] [ Designated as safety issue: Yes ]
  • Immune reconstitution of CD3, CD3/CD4/CD8, CD56, CD19 cells [ Time Frame: 3 months after HCT ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: 24 months after HCT ] [ Designated as safety issue: Yes ]
  • Incidence of graft versus host disease [ Time Frame: 6 months after HCT ] [ Designated as safety issue: Yes ]
  • Disease free survival [ Time Frame: 24 months after HCT ] [ Designated as safety issue: Yes ]
  • Disease response [ Time Frame: 12 months after HCT ] [ Designated as safety issue: Yes ]
  • Disease response [ Time Frame: 24 months after HCT ] [ Designated as safety issue: Yes ]
  • Immune reconstitution of CD3, CD3/CD4/CD8, CD56, CD19 cells [ Time Frame: 6 months after HCT ] [ Designated as safety issue: Yes ]
  • Immune reconstitution of CD3, CD3/CD4/CD8, CD56, CD19 cells [ Time Frame: 12 months after HCT ] [ Designated as safety issue: Yes ]
  • Immune reconstitution of CD3, CD3/CD4/CD8, CD56, CD19 cells [ Time Frame: 24 months after HCT ] [ Designated as safety issue: Yes ]
  • Incidence of graft versus host disease [ Time Frame: 12 months after HCT ] [ Designated as safety issue: Yes ]
  • Incidence of graft versus host disease [ Time Frame: 24 months after HCT ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: April 2012
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: immunosuppression
    Conditioning with treosulfan 14 g/m2 day -6 to -4, fludarabine 30 mg/m2/24h day-6 to -2, ATG-Fresenius 20 mg/kg day -4 to -2, rituximab 500 mg/m2 day -1. Unmanipulated PBSC day 0. Postgrafting immunosuppression with mycophenolate mofetil (15 mg/kg TID) and sirolimus (2 mg QD).
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01582048

Contacts
Contact: Wolfgang A Bethge, MD +49-7071-2983176 wolfgang.bethge@med.uni-tuebingen.de

Locations
Germany
Hematology/Oncology Medical Center University Hospital of Mainz Recruiting
Mainz, Germany, D-55101
Contact: Eva M Wagner, MD       eva.wagner@unimedizin-mainz.de   
Principal Investigator: Eva M Wagner, MD         
Bone Marrow Transplantation Unit Medical Center University Hospital of Nuernberg Recruiting
Nuernberg, Germany, D-90419
Contact: K Schaefer-Eckart, MD       Kerstin.Schaefer-Eckart@klinikum-nuernberg.de   
Principal Investigator: K Schaefer-Eckart, MD         
Department of Hematology/Oncology Medical Center University Hospital of Tuebingen Recruiting
Tuebingen, Germany, D-72076
Contact: Wolfgang A Bethge, MD    +49-7071-2983176    wolfgang.bethge@med.uni-tuebingen.de   
Principal Investigator: Wolfgang A Bethge, MD         
BMT-Unit Deutsche Klinik für Diagnostik Recruiting
Wiesbaden, Germany, D-65191
Contact: Gernot Stuhler, MD       kmt@dkd-wiesbaden.de   
Contact: Michael Schleuning, MD       kmt@dkd-wiesbaden.de   
Principal Investigator: Gernot Stuhler, MD         
Sub-Investigator: Herrad Baurmann, MD         
Sponsors and Collaborators
Prof. Dr. med. Wolfgang Bethge
medac GmbH
Pfizer
Neovii Biotech
Investigators
Principal Investigator: Wolfgang A Bethge, MD Medical Center University Hospital of Tuebingen
  More Information

No publications provided

Responsible Party: Prof. Dr. med. Wolfgang Bethge, Associate Professor Hematology/Oncology, University Hospital Tuebingen
ClinicalTrials.gov Identifier: NCT01582048     History of Changes
Other Study ID Numbers: E:531/2011, 2011-002192-41
Study First Received: April 16, 2012
Last Updated: May 28, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Mycophenolate mofetil
Mycophenolic Acid
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014