Clinical trial NCT01582048: Multicenter Study of Peritransplantation Immunosuppression for Mismatched Hematopoietic Cell Transplantation After Reduced Intensity Conditioning
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Patients Receiving Mismatched Allogeneic HCT
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
Collaborators: name: medac GmbH
name: Pfizer
name: Neovii Biotech
First posted: 2012-04-20
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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


Eligibility 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

Primary outcomes:
measure: Treatment related mortality
timeFrame: 12 months after HCT
measure: Treatment related mortality
timeFrame: 24 months after HCT
Secondary outcomes:
measure: Toxicity according CTC of protocol on day 100
timeFrame: on day 100
measure: Engraftment on day 100
timeFrame: on day 100
measure: Overall survival
timeFrame: 12 months after HCT
measure: Incidence of graft versus host disease
timeFrame: 3 months after HCT
measure: Incidence of infections
timeFrame: 2 years after HCT
measure: Immune reconstitution of CD3, CD3/CD4/CD8, CD56, CD19 cells
timeFrame: 3 months after HCT
measure: Overall survival
timeFrame: 24 months after HCT
measure: Incidence of graft versus host disease
timeFrame: 6 months after HCT
measure: Disease free survival
timeFrame: 24 months after HCT
measure: Disease response
timeFrame: 12 months after HCT
measure: Disease response
timeFrame: 24 months after HCT
measure: Immune reconstitution of CD3, CD3/CD4/CD8, CD56, CD19 cells
timeFrame: 6 months after HCT
measure: Immune reconstitution of CD3, CD3/CD4/CD8, CD56, CD19 cells
timeFrame: 12 months after HCT
measure: Immune reconstitution of CD3, CD3/CD4/CD8, CD56, CD19 cells
timeFrame: 24 months after HCT
measure: Incidence of graft versus host disease
timeFrame: 12 months after HCT
measure: Incidence of graft versus host disease
timeFrame: 24 months after HCT
Other outcomes:
Locations:
city: Mainz
country: Germany
facility: Hematology/Oncology Medical Center University Hospital of Mainz
city: Nuernberg
country: Germany
facility: Bone Marrow Transplantation Unit Medical Center University Hospital of Nuernberg
city: Tuebingen
country: Germany
facility: Department of Hematology/Oncology Medical Center University Hospital of Tuebingen
city: Wiesbaden
country: Germany
facility: BMT-Unit Deutsche Klinik für Diagnostik
Study officials:
affiliation: Medical Center University Hospital of Tuebingen
name: Wolfgang A Bethge, MD
role: PRINCIPAL_INVESTIGATOR
References: