NCT01814488

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
101

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jul 2013

Typical duration for phase_2

Geographic Reach
1 country

30 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 14, 2013

Completed
6 days until next milestone

First Posted

Study publicly available on registry

March 20, 2013

Completed
3 months until next milestone

Study Start

First participant enrolled

July 1, 2013

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2017

Completed
Last Updated

March 10, 2023

Status Verified

March 1, 2023

Enrollment Period

4 years

First QC Date

March 14, 2013

Last Update Submit

March 9, 2023

Conditions

Keywords

Active acute leukemiaPIFAllogeneic transplantAcute Myeloid LeukemiaAcute Lymphoblastic LeukemiaMarrow Unrelated DonorCord BloodFamily Haploidentical donor

Outcome Measures

Primary Outcomes (5)

  • Overall Survival (OS)

    The overall survival at 2 years (from time of enrolment) of all patients enrolled in to the study (either transplanted or not). This is the simplest outcome, defined as the probability of survival irrespective of disease state at any point in time. Patients alive at their last follow-up are censored. It is analyzed by the Kaplan-Meier method, Log-Rank Test and parametric or semiparametric survival models.

    2 years from time of enrolment

  • Disease-Free Survival (DFS)

    DFS is defined as the probability of being alive free of disease at any point in time. Thus, death or disease relapse are treated as events (1). Patients alive and free of disease at their last follow-up are censored. The statistical methods for the analysis of DFS are the same as for OS (Kaplan-Meier curve, Log-Rank Test and survival models).

    2 years from enrolment

  • Relapse Incidence (RI)

    RI is defined as the probability of having had a relapse before time t. Death without experiencing a relapse is a competing event. The correct method of analysis is therefore the estimation of the Cumulative Incidence curve, comparable by the Gray Test and, for the multivariate analysis, the application of the proportional hazard model for the sub-distribution of competing risks, by Fine and Gray. In studying relapse, sometimes the interest is not only in the estimation of the cumulative incidence curve, but also in the estimation of the hazard ratios for comparing groups of patients. It is therefore common to apply also a survival (Cox or parametric) model considering relapse as an event and death without relapse as a censoring (the response time is given by the minimum between time to relapse and time to death without relapse; as usual, a patient who is alive and free of relapse is also censored).

    2 years from enrolment

  • Non-Relapse Mortality (NRM)

    It is defined as the probability of dying without previous occurrence of a relapse, which is a competing event. The same indications as for the analysis of RI apply.

    2 years from enrolment

  • Progression-Free Survival (PFS)

    It is defined as the probability of being alive with no indication of disease progression (relapse is considered as progression for patients in CR). It is analyzed by KaplanMeier curve, Log-Rank Test and parametric or non-parametric survival models.

    2 years from enrolment

Secondary Outcomes (3)

  • Haematopoietic Recovery

    participants will be followed for the duration of hospital stay, an expected average of 30 days

  • Acute Graft-versus-Host Disease (aGvHD)

    from date of transplant to until the date of first event of aCGVD assessed up to 100 days post transplant

  • Chronic Graft-versus-Host Disease (cGvHD)

    from day +100 post transplant to until the date of first event to cGVHD assessed up to 2 years post enrolment

Study Arms (1)

allogenic transplant

EXPERIMENTAL

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.

Procedure: allogeneic transplant

Interventions

Allogenic transplant using either a Marrow Unrelated Donor or a Cord Blood unit or a family Haploidentical donor. The conditioning regimen in standard use is: Thiotepa (Tepadina) i.v. 5 mg/kg/daily (total dose 10 mg/kg) day -7 and -6; Busulfan (Busilvex) i.v. 3,2 mg/kg/day (total dose 9,6 mg/kg) as a single daily dose day -5, -4, -3; Fludarabine i.v. 50 mg/m2 (total dose150 mg/m2) day -5, -4, -3. Primary antifungal prophylaxis is Micafungin 50 mg/die i.v. (1 mg/kg if \<40 kg) day 0 to engraftment. After engraftment continue antifungal prophylaxis according to local practice.

Also known as: Marrow Unrelated or Cord Blood or family Haploidentical donor
allogenic transplant

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • Previous allogeneic transplant (autologous transplant is accepted)
  • Positive pregnancy test
  • Any active, uncontrolled infection.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (30)

Azienda Ospedaliera SS Antonio e Biagio

Alessandria, Italy

Location

Policlinico

Bari, Italy

Location

Divisione di Ematologia - Ospedali Papa Giovanni XXIII

Bergamo, Italy

Location

Ospedale San Orsola

Bologna, Italy

Location

Ospedale Regionale Generale- Divisione Ematologia

Bolzano, Italy

Location

Ospedale Binaghi

Cagliari, Italy

Location

Ospedale Oncologico Businco

Cagliari, Italy

Location

Ospedale Ferrarotto - Ematologia

Catania, Italy

Location

S.C. Ematologia - Azienda Ospedaliera S. Croce e Carle

Cuneo, Italy

Location

Cattedra di Ematologia - Azienda Ospedaliera di Careggi

Florence, Italy

Location

Ospedale Policlinico San Martino - IST

Genova, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Italy

Location

Ospedale Niguarda Ca' Grande

Milan, Italy

Location

Ospedale San Raffaele

Milan, Italy

Location

Divisione Ematologia - Azienda Ospedaliera Universitaria - Policlinico -

Modena, Italy

Location

Cattedra di Medicina Interna ed Ematologia - Ospedale S. Gerardo de' i Tintori - Università degli Studi di Milano

Monza, Italy

Location

AO Ospedali Riuniti Villa Sofia - Cervello

Palermo, Italy

Location

Dipartimento Oncologico La Maddalena

Palermo, Italy

Location

Fondazione IRCCS San Matteo

Pavia, 27100, Italy

Location

Dip. di Ematologia - Unità di Terapia Intensiva Ematologica per il Trapianto Emopoietico - Ospedale Civile di Pescara

Pescara, Italy

Location

Ospedale G. Da Saliceto di Piacenza

Piacenza, Italy

Location

Cattedra di Ematologia - Policlinico

Roma, Italy

Location

Policlinico A. Gemelli

Roma, Italy

Location

Policlinico Universitario Tor Vergata

Roma, Italy

Location

U.O. di Ematologia e Trapianti di Midollo Osseo - Azienda Osp. S. Camillo-Forlanini / Padiglione Morgagni

Roma, Italy

Location

Ematologia e Centro Trapianti Midollo Osseo - Ospedale IRCCS Casa Sollievo della Sofferenza

San Giovanni Rotondo, Italy

Location

Ospedale San Giuseppe Moscato

Taranto, Italy

Location

Azienda ospedaliera Città della Salute e della Scienza

Torino, Italy

Location

Centro Trapianti Metropolitano

Torino, Italy

Location

A.O. Santa Maria della Misericordia

Udine, Italy

Location

MeSH Terms

Conditions

Leukemia, Myeloid, AcutePrecursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Transplantation, Homologous

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLeukemia, LymphoidLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

TransplantationSurgical Procedures, Operative

Study Officials

  • Fabio Ciceri, MD

    Ospedale San Raffaele

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 14, 2013

First Posted

March 20, 2013

Study Start

July 1, 2013

Primary Completion

June 30, 2017

Study Completion

June 30, 2017

Last Updated

March 10, 2023

Record last verified: 2023-03

Locations