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Acute LeukemiaPhase 2Gandalf-01NCT01814488

A Phase II Study on Allogeneic Stem Cell Transplantation in Patients With Active Acute Leukemia

A Phase 2 study testing allogeneic transplant in people with Acute Leukemia, run by Gruppo Italiano Trapianto di Midollo Osseo at 30 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Acute Leukemia
What is being tested?
allogeneic transplant
Could I receive a placebo?
No, everyone receives an active treatment
How many people
101 participants
Where
30 sitesItaly
Study dates
Jul 2013to 30 Jun 2017
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

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

Trial locations and contacts

30 sites in 1 country.

30 sites in 1 country

Italy30 sites

  • Azienda Ospedaliera SS Antonio e Biagio

    Alessandria

  • Policlinico

    Bari

  • Divisione di Ematologia - Ospedali Papa Giovanni XXIII

    Bergamo

  • Ospedale San Orsola

    Bologna

  • Ospedale Regionale Generale- Divisione Ematologia

    Bolzano

  • Ospedale Binaghi

    Cagliari

  • Ospedale Oncologico Businco

    Cagliari

  • Ospedale Ferrarotto - Ematologia

    Catania

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

    Cuneo

  • Cattedra di Ematologia - Azienda Ospedaliera di Careggi

    Florence

  • Ospedale Policlinico San Martino - IST

    Genova

  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

    Milan

  • Ospedale Niguarda Ca' Grande

    Milan

  • Ospedale San Raffaele

    Milan

  • Divisione Ematologia - Azienda Ospedaliera Universitaria - Policlinico -

    Modena

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

    Monza

  • AO Ospedali Riuniti Villa Sofia - Cervello

    Palermo

  • Dipartimento Oncologico La Maddalena

    Palermo

  • Fondazione IRCCS San Matteo

    Pavia, 27100

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

    Pescara

  • Ospedale G. Da Saliceto di Piacenza

    Piacenza

  • Cattedra di Ematologia - Policlinico

    Roma

  • Policlinico A. Gemelli

    Roma

  • Policlinico Universitario Tor Vergata

    Roma

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

    Roma

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

    San Giovanni Rotondo

  • Ospedale San Giuseppe Moscato

    Taranto

  • Azienda ospedaliera Città della Salute e della Scienza

    Torino

  • Centro Trapianti Metropolitano

    Torino

  • A.O. Santa Maria della Misericordia

    Udine

Other trials in Italy

About this study

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

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.

Read the 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.

Conditions
Acute Leukemia
Being tested
allogeneic transplant
Keywords
Active acute leukemia, PIF, Allogeneic transplant, Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Marrow Unrelated Donor, Cord Blood, Family Haploidentical donor
Medical subject headings
Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • allogeneic transplantProcedure or surgery

    Also called Marrow Unrelated or Cord Blood or family Haploidentical donor

    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.

Study groups in NCT01814488
Study groupRoleWhat they receive
allogenic transplantExperimentalThe 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.
Receives: Procedure: allogeneic transplant

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 2 years from time of enrolment

  2. 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).

    Measured: 2 years from enrolment

  3. 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).

    Measured: 2 years from enrolment

  4. 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.

    Measured: 2 years from enrolment

  5. 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.

    Measured: 2 years from enrolment

Secondary outcomes (3)

  1. Haematopoietic Recovery

    The day of engraftment is defined as the first day of 3 consecutive days with a persistent blood cell count above a predefined level:

    WBC 1 x 109/l PMN 0.5 x 109/l Platelets 50 x109 /l or 20x 10 9 /l Death without recovery is a competing event, while no engraftment at the last followup is to be considered as a censored observation. Relapse or disease progression could be considered (depending on the disease being studied) as further competing events: this must be discussed with the responsible physician.

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

  2. Acute Graft-versus-Host Disease (aGvHD)

    The available information in the EBMT data regard the date of onset and the maximum grade of aGvHD. It is therefore possible to estimate the probability of aGvHD in a competing risks setting (death is a competing event; whether relapse/progression is a competing event must be discussed with the physician). By definition, patients alive (relapse/progression-free) at day 100 without having experienced aGvHD are censored. If the dates of onset are missing for the majority of patients, the analysis can focus only on the occurrence of aGvHD, which is analyzed by a logistic regression model. This method would however be incorrect if there is a (non negligible) percentage of censored observations or if competing events occurred before day 100.

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

  3. Chronic Graft-versus-Host Disease (cGvHD)

    When possible, if information on the date of 1°occurrence of cGvHD is available, it should be analyzed as a time-to-event outcome, being death (and possibly relapse/progression) the competing event; data are censored for patients alive (relapse/progression-free) without episodes of cGvHD at last follow-up. Since cGvHD is defined only for patients surviving at least 100 days, the survival model should consider a left truncation at 100 days; alternatively, the time of occurrence of cGvHD must be computed from 100 days. If information on the timing of cGvHD is not available, the outcome considered is the occurrence, and the statistical model to be used is the logistic regression. Only patients surviving at least 100 days are considered to be at risk of developing cGvHD, therefore the analysis must be restricted to these patients. This analysis is of course not satisfactory because it does not take into account the occurrence of death and censoring.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Mar 2013 (estimated)
  2. Study startJul 2013
  3. Primary completion30 Jun 2017
  4. Study completion30 Jun 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
101 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01814488
Sponsor's protocol ID
2012-004008-37 Gandalf-01
Acronym
Gandalf-01
Status last verified
Mar 2023
First submitted
14 Mar 2013
Last updated
10 Mar 2023
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing allogeneic transplant in people with Acute Leukemia, run by Gruppo Italiano Trapianto di Midollo Osseo at 30 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) (time frame: 2 years from time of enrolment). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01814488.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2023.

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