Clinical trial NCT01814488: A Phase II Study on Allogeneic Stem Cell Transplantation in Patients With Active Acute Leukemia
Official title: A Phase II Multicentre Open-label Study on Allogeneic Stem Cell Transplantation From Unrelated, Cord-blood and Family Haploidentical Donors in Patients With Active Acute Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Leukemia
Keywords: Active acute leukemia
PIF
Allogeneic transplant
Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Marrow Unrelated Donor
Cord Blood
Family Haploidentical donor
Lead sponsor: Gruppo Italiano Trapianto di Midollo Osseo
Sponsor class: OTHER
First posted: 2013-03-20
Enrollment: 101
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The experimental treatment consists in the application of a therapeutic strategy of allogeneic transplantation as a potential curative procedure in a population of patients with chemoresistant acute leukemias.

Therapeutic intervention, namely the conditioning regimen as well as GVHD prophylaxis, are based on regimens currently in standard use in the context of allogeneic transplantation.

Detailed description: The experimental treatment consists in the application of a therapeutic strategy of allogeneic transplantation using either a Marrow Unrelated Donor (MUD) or a Cord Blood (CB) unit or a family Haploidentical (Haplo) donor as a potential curative procedure in a population of patients with chemoresistant acute leukemias for increase the overall survival in this patients.

Therapeutic intervention, namely the conditioning regimen as well as GVHD prophylaxis, are based on regimens currently in standard use in the context of allogeneic transplantation.

The Data Safety Monitoring Board (DSMB) in collaboration with the Steering Committee (SC) will make periodic monitoring to ensure the safety of patients enrolled in to the study. In particular, DSMB will check the periodic safety reports of serious adverse events, the primary or secondary graft failure and treated related mortality (TRM) data generated by the Data Management Center. A safety report will be generated every 30 enrolled patients completed 100 days of follow-up.

The population for analysis in the trial will be the Intention to Treat (ITT) population. All patients enrolled in the study will be included in the ITT analysis.

This study will explore the feasibility, safety and efficacy of allogeneic stem cell transplantation from unrelated, cord-blood and haploidentical donor in patients with an active leukemia. Due to the lack of detailed information from literature and the absence of alternative curative options in this patient population, criteria for sample size assessment do not refer to a formal statistical power calculation. Therefore, GITMO will promote enrollment of all patients with active leukemia eligible to allogeneic SCT in all Italian centres with the aim to collect outcome variables in ITT in the widest and most representative cohort of this specific patient population.

The choice of 80 patients transplanted is based on feasibility reasons and the expected patient population with these characteristics referred to the main Italian Transplant Centres in two year. GITMO survey data on transplant activity points to an estimated accrual of 40 patients per year over a 24 months enrolment period. Criteria for defining sample size do not follow statistical power estimates in order to demonstrate difference between the alternative donor options.

Eligibility criteria: Inclusion Criteria:

Diagnosis of Primary induction Failure or chemoresistant relapse in Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL) patients

Activation of an alternative donor search by the Italian Bone Marrow Donor Registry (IBMDR)

Age \>=18\<=70

Unavailability of a HLA-matched related donor (MRD)

Performance status: ECOG\<=3

Written and signed informed consent

Life expectancy not severely limited by concomitant illness.

Exclusion Criteria:

Previous allogeneic transplant (autologous transplant is accepted)

Positive pregnancy test

Any active, uncontrolled infection.

-

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: 2 years from time of enrolment
measure: Disease-Free Survival (DFS)
timeFrame: 2 years from enrolment
measure: Relapse Incidence (RI)
timeFrame: 2 years from enrolment
measure: Non-Relapse Mortality (NRM)
timeFrame: 2 years from enrolment
measure: Progression-Free Survival (PFS)
timeFrame: 2 years from enrolment
Secondary outcomes:
measure: Haematopoietic Recovery
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 30 days
measure: Acute Graft-versus-Host Disease (aGvHD)
timeFrame: from date of transplant to until the date of first event of aCGVD assessed up to 100 days post transplant
measure: Chronic Graft-versus-Host Disease (cGvHD)
timeFrame: from day +100 post transplant to until the date of first event to cGVHD assessed up to 2 years post enrolment
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: Azienda Ospedaliera SS Antonio e Biagio
city: Bari
country: Italy
facility: Policlinico
city: Bergamo
country: Italy
facility: Divisione di Ematologia - Ospedali Papa Giovanni XXIII
city: Bologna
country: Italy
facility: Ospedale San Orsola
city: Bolzano
country: Italy
facility: Ospedale Regionale Generale- Divisione Ematologia
city: Cagliari
country: Italy
facility: Ospedale Binaghi
city: Cagliari
country: Italy
facility: Ospedale Oncologico Businco
city: Catania
country: Italy
facility: Ospedale Ferrarotto - Ematologia
city: Cuneo
country: Italy
facility: S.C. Ematologia - Azienda Ospedaliera S. Croce e Carle
city: Firenze
country: Italy
facility: Cattedra di Ematologia - Azienda Ospedaliera di Careggi
city: Genova
country: Italy
facility: Ospedale Policlinico San Martino - IST
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: Ospedale Niguarda Ca' Grande
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Modena
country: Italy
facility: Divisione Ematologia - Azienda Ospedaliera Universitaria - Policlinico -
city: Monza
country: Italy
facility: Cattedra di Medicina Interna ed Ematologia - Ospedale S. Gerardo de' i Tintori - Università degli Studi di Milano
city: Palermo
country: Italy
facility: AO Ospedali Riuniti Villa Sofia - Cervello
city: Palermo
country: Italy
facility: Dipartimento Oncologico La Maddalena
city: Pavia
country: Italy
facility: Fondazione IRCCS San Matteo
city: Pescara
country: Italy
facility: Dip. di Ematologia - Unità di Terapia Intensiva Ematologica per il Trapianto Emopoietico - Ospedale Civile di Pescara
city: Piacenza
country: Italy
facility: Ospedale G. Da Saliceto di Piacenza
city: Roma
country: Italy
facility: Cattedra di Ematologia - Policlinico
city: Roma
country: Italy
facility: Policlinico A. Gemelli
city: Roma
country: Italy
facility: Policlinico Universitario Tor Vergata
city: Roma
country: Italy
facility: U.O. di Ematologia e Trapianti di Midollo Osseo - Azienda Osp. S. Camillo-Forlanini / Padiglione Morgagni
city: San Giovanni Rotondo
country: Italy
facility: Ematologia e Centro Trapianti Midollo Osseo - Ospedale IRCCS Casa Sollievo della Sofferenza
city: Taranto
country: Italy
facility: Ospedale San Giuseppe Moscato
city: Torino
country: Italy
facility: Azienda ospedaliera Città della Salute e della Scienza
city: Torino
country: Italy
facility: Centro Trapianti Metropolitano
city: Udine
country: Italy
facility: A.O. Santa Maria della Misericordia
Study officials:
affiliation: Ospedale San Raffaele
name: Fabio Ciceri, MD
role: PRINCIPAL_INVESTIGATOR
References: