Clinical trial NCT01020175: Peripheral Blood (PB) Versus Bone Marrow (BM) in Allogeneic Stem Cell Transplantation
Official title: A Phase III, Randomized, Multicentre Trial Comparing Allogeneic Filgrastim Mobilised Peripheral Blood Progenitor Cell Transplantation (PBPCT) With Allogeneic Bone Marrow Transplantation (BMT) in Patients With Acute Leukemia, Chronic Myelogenous Leukemia or Myelodysplastic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Leukemia
Chronic Myelogenous Leukemia
Myelodysplastic Syndrome
Keywords: allogeneic transplantation
Leukemia
GvHD
MDS
Lead sponsor: European Society for Blood and Marrow Transplantation
Sponsor class: NETWORK
Collaborators: name: Amgen
name: Hoffmann-La Roche
First posted: 2009-11-25
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 350 patients with early leukemias were assigned to receive peripheral blood or bone marrow transplantation; the occurrence of acute and chronic graft versus host disease, survival, transplantation-related mortality, and relapse rates were compared.

Detailed description: The trial was designed to investigate the safety and outcome of allogeneic filgrastim-mobilized PBPCT compared with allogeneic BMT in patients with standard-risk leukemia. A total of 350 patients between 18 and 55 years of age with acute leukemias in remission or chronic myelogenous leukemia in first chronic phase were randomized to receive either filgrastim-mobilized peripheral blood progenitor cells or bone marrow cells from HLA-identical sibling donors after standard high-dose chemoradiotherapy. The study was approved by the ethics committees of all participating centers, and all patients and donors gave informed consent before any study-related procedure was performed. Donor-recipient pairs were randomized to undergo either BMT or PBPCT. Randomization was carried out centrally at the International Institute for Drug Development (id2), Brussels, Belgium, and used the minimization method to allocate donor and recipient to allogeneic BMT or PBPCT. The randomization strata were as follows: diagnosis (chronic myeloid leukemia \[CML\] vs other diseases), sex mismatch of donor and recipient, and whether the donor was female and nulliparous. Follow-up visits were scheduled for 6, 12, 24, and 36 months after the date of transplantation.

Neutrophil and platelet recovery occurred significantly faster after transplantation of peripheral blood progenitor cells than after bone marrow transplantation. Acute graft versus host disease of grades II-IV was significantly more frequent in recipients of peripheral blood progenitor cells than in recipients of marrow cells The cumulative incidence of chronic graft versus host disease was higher with peripheral blood progenitor cells than with bone marrow cells

Eligibility criteria: Inclusion Criteria:

* Patients with either diagnosis of AML in first or second remission, in first untreated relapse (blast count in marrow \< 30%); ALL in first or second remission, in first untreated relapse (blast count in marrow \< 30%); CML in first chronic phase, in first accelerated phase (total blast and promyelocytes in marrow and or peripheral blood \< 30%) or MDS (excluding RAEB-t).
* Age between 18 and 55 years.
* ECOG performance status between 0,1 or 2.
* HLA-identical sibling donor.
* Written informed consent.

Exclusion Criteria:

* Serum creatinine more than 10% above the normal range for the centre.
* Left ventricular size and function abnormal.
* DLCO \< 50%.
* Bilirubin \> 2mg/dL (34.2 µmol/L).
* Splenectomised or splenic irradiation.
* Psychiatric, addictive, or any other disorder, which compromises ability to give truly informed consent for participation in this study.
* Currently receiving non-licensed drugs which may affect GVHD or engraftment.
* Pregnant or lactating women.
* Known sensitivity to E.coli derived products.
* HIV positive.
* Previously received BM/PBPC transplant.

Primary outcomes:
measure: The primary end point of the study was the maximum grade of acute graft versus host (GVH) disease observed in the recipient.
Secondary outcomes:
measure: Incidence of acute GVH disease grade II or above
measure: Time to acute GVH disease
measure: Time to an unsupported platelet count of 20 _ 109/L and 50 _ 109/L
measure: Time to absolute neutrophil count (ANC) of 0.5 x 10e9/L and 1 x 10e9/L
measure: Incidence and severity of chronic GVH disease
measure: Leukemia-free survival
measure: Overall survival
Other outcomes:
Locations:
city: Hamburg
country: Germany
facility: Dr. Norbert Schmitz
Study officials:
affiliation: Christian-Albrechts- Universita¨t, Kiel, Germany
name: Nobert Schmitz, Prof.
role: STUDY_CHAIR
affiliation: Allgemeines Krankenhaus, Vienna, Austria
name: H Greinix, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Innsbruck, Austria
name: D Niederwieser, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Leuven, Belgium
name: M. Boogaerts, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Cliniques Universitaires St Luc, Brussels, Belgium
name: A Ferrant, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Charite der Humboldt Universität, Berlin, Germany
name: R. Arnold, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital St Louis, Paris, France
name: E Gluckman, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Hoˆpital St Antoine, Paris, France
name: N C Gorin, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Universita¨t Ulm, Germany
name: N Frickhofen, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Christian-Albrechts- Universita¨t, Kiel, Germany
name: P Dreger, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitätsklinikum Eppendorf, Hamburg, Germany
name: A Zander, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: St James Hospital, Dublin, Ireland
name: S McCann, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Hadassah University Hospital, Jerusalem, Israel
name: A Nagler, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale San Martino, Genova, Italy
name: A Bacigalupo, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Kantonsspital, Basel, Switzerland
name: A Gratwohl, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Hammersmith Hospital, London, United Kingdom
name: J Apperley, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Nottingham City Hospital, United Kingdom
name: N H Russell, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Huddinge Hospital, Sweden
name: O Ringde´n, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale V Cervello-USL, Palermo, Italy
name: I Majolino, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Claude Huriez, Lille, France
name: J P Jouet, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Necker, Paris, France
name: B Varet, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Klinikum der Albert-Ludwigs-Universität, Freiburg, Germany
name: J Finke, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Leeds General Infirmary, United Kingdom
name: G. Smith, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Azienda Ospedaliera Careggi, Firenze, Italy
name: A Bosi, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Padiglione G Marcora, Ospedale Maggiore di Milano, Italy
name: G Lambertenghi-Deliliers, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitatsklinikum, Mainz, Germany
name: K Kolbe, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Helsinki University CT. Rentral Hospital, Finland
name: T Ruutu, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Westmead Hospital, Australia
name: K A Bradstock), Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: LCHRU de Hautepierre, Strasbourg, France
name: B Lioure, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Hanson Centre for Cancer Research, Royal Adelaide Hospital, Australia
name: T Hughes, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Melbourne Hospital, Parkville, Australia
name: J Szer, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Perth Hospital, Australia
name: R Herrmann, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitätsklinik, Homburg, Germany
name: L Tru¨mper, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro Dipartimentale Trapianti di Midollo, Ospedale Molinette, Torino, Italy
name: M Falda, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Ankara University Medical Facility, Turkey
name: M Beksac, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Evangelismos General Hospital, Athens, Greece
name: E Nikiforakis, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto Portugues de Oncologia Francisco Gentil, Lisboa, Portugal
name: M Abecasis, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Rambam Medical Center, Haifa, Israel
name: J Rowe, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Free Hospital Hampstead, London, United Kingdom
name: M Potter, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Medizinische Klinik Nurnberg, Germany
name: H Wandt, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Stiftung Deutsche Klinik f. Diagnostik, Wiesbaden, Germany
name: R Schwerdtfeger, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: University Rostock, Germany
name: J Casper, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: King's College Hospital, London, United Kingdom
name: A. Pagliuca, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Friedrichs B, Tichelli A, Bacigalupo A, Russell NH, Ruutu T, Shapira MY, Beksac M, Hasenclever D, Socie G, Schmitz N. Long-term outcome and late effects in patients transplanted with mobilised blood or bone marrow: a randomised trial. Lancet Oncol. 2010 Apr;11(4):331-8. doi: 10.1016/S1470-2045(09)70352-3. Epub 2010 Jan 30.