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Acute Lymphoblastic LeukemiaPhase 2NCT00358072

Treatment of Adult ALL With an MRD-directed Programme.

A Phase 2 study testing Postremission consolidation based on MRD status in people with Acute Lymphoblastic Leukemia, run by Northern Italy Leukemia Group at 15 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 study aims to optimize the concept of risk-oriented postremission consolidation therapy, by offering (i) standard consolidation-maintenance to patients at lowest risk of relapse as defined by MRD(Minimal Residual Disease) negative status, and (ii) allogeneic stem cell transplantation (related/unrelated donor… Read more about this study

Who is it for?
Ages 15 to 65 years
Conditions the study is for
Acute Lymphoblastic Leukemia
What is being tested?
Postremission consolidation based on MRD status
Could I receive a placebo?
No, everyone receives an active treatment
How many people
280 participants
Where
15 sitesItaly
Study dates
May 2000to Sep 2008
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 15 to 65 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Untreated Acute lymphoblastic leukemia or lymphoblastic lymphoma (T-cell, precursor B-cell)
  • Age 15-65 years (older patients if biologically fit according to responsible physician)
  • Written informed consent

Who cannot join

  • Any co-morbidity precluding the administration of intensive chemotherapy for adult ALL

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

Italy15 sites

  • Ospedali Riuniti di Bergamo

    Bergamo, BG, 24128

  • Divisione di Ematologia e TMO Ospedale San Maurizio

    Bolzano, BZ, 39100

  • Divisione Ematologia Spedali Civili

    Brescia, BS, 25123

  • U.O. Ematologia e Centro TMO Ospedale Armando Businco

    Cagliari, CA, 09121

  • U.S. Ematologia - Centro TMO Istituti Ospedalieri

    Cremona, CR, 26100

  • Ematologia Azienda Ospedaliera S.Croce e Carle

    Cuneo, CN, 12100

  • Ematologia AOU Careggi

    Florence, FI, 50134

  • Divisione Ematologia Ospedale Umberto I

    Mestre, VE, 30172

  • Ematologia Centro TMO Fondazione IRCSS Ospedale Maggiore

    Milan, MI, 20122

  • Ematologia e TMO Ospedale San Raffaele

    Milan, MI, 20132

  • Ematologia - TMO Ospedale San Gerardo

    Monza, MI, 20052

  • Oncologia ed Ematologia Oncologica Institution Regione Veneto, ULSS n.13 - Presidi Ospedalieri di Noale, Mirano, Dolo

    Noale, VE, 30033

  • Oncoematologia e TMO Dipartimento Oncologico

    Palermo, PA, 90146

  • Ematologia 2 Ospedale San Giovanni Battista

    Torino, TO, 10126

  • Ematologia Ospedale San Bortolo

    Vicenza, VI, 36100

Other trials in Italy

About this study

Official title: Treatment of Adult Acute Lymphoblastic Leukemia Using a Post-remission Programme Whose Intensity Varies Depending on the Risk Class Defined on the Basis of Minimal Residual Disease.

The study aims to optimize the concept of risk-oriented postremission consolidation therapy, by offering (i) standard consolidation-maintenance to patients at lowest risk of relapse as defined by MRD(Minimal Residual Disease) negative status, and (ii) allogeneic stem cell transplantation (related/unrelated donor available) or multicycle high-dose therapy with autologous blood stem cell transplant (no donor) to patients at highest risk of relapse as defined by MRD+ status.

The prognostic role of MRD evaluation in unselected patients will be evaluated.

Read the detailed description

Improved outcome of adult ALL through the application of:

  • Risk-adapted induction (cycle no. 1: IVAP i.e idarubicin-vincristine-asparaginase-prednisone, plus fractionated cyclophosphamide in T-ALL,and imatinib in Ph/BCR-ABL+ ALL)
  • Risk stratification (clinical) according to morphology, immunophenotype, cytogentics and molecular biology results. Standard risk (SR) is defined by pre-B CD10+ phenotype, Ph/BCR-ABL- status, and a blast count <10x10e9/L. All other subgroups are HR (high-risk) except for Ph/BCR-ABL+ and t(4;11)+ ALL (VHR, very high-risk)
  • Homogeneous early consolidation programme including both conventional therapy with idarubicin-vincristine-cyclophosphamide-dexamethasone/prednisone(cycles no. 2,3,5,6,8) and high-dose treatemt with MTX/Ara-C (cycles no. 4,7) and meningeal prophylaxis (triple intrathecal therapy x8-12, skull irradiation), plus imatinib in Ph+ ALL (Phase A). Autologous bllo stem cells are mobilized and cryopreserved after cycle no. 4.
  • Serial evaluation of minimal residual disease (MRD) with RQ-PCT technology, aiming to define in individual patients the rate of reduction during early consolidation. The molecular study was centralized and aimed at obtaining one or more patient-specific probe(s)with a sensitivity of at least 10e-3. Patient bone marrow was sampled for MRD analysis at timepoints 13 i.e. after cycles no.3,5, and 7. Only patients with a negative result at timepoint 3 and a negative/low positive (<10e-4) result at timepoint 3 are considered MRD-, all other combinations being regarded MRD+.
  • Phase B therapy according to MRD results and ALL subset:
  • MRD- nonPh/t(4;11): standard maintenance
  • MRD+ nonPh/t(4;11): allogeneic stem cell transplantation (from sibling/MUD) or, alternatively, intensified high-dose therapy (2-4 "hypercycles")with autologous stem cell support and anti CD20 MoAb (if CD20+), followed by maintenance. Each "hypercycle" consists of high-dose mercaptopurine-etoposide-melphalan (cycles no. 1,3) or methotrexate-cytarabine (cycles no. 2,4)
  • MRD unknown nonPh/t(4;11): treatment by clinical risk (SR: maintenance; HR, as per MRD+)
  • Ph/t(4;11)+: allogeneic stem cell transplantation as soon as possible into complete remission; if a transplant is not possible, consolidation is as for HR patients. each cycle is supplemented by imatinib in Ph+ ALL

The illustrated strategy aims to optimize postremission consolidation therapy by offering standard treatment "only" to patients at lowest risk of relapse (MRD-), thereby reducing the risks of high dose treatments (expected TRM from allogeneic SCT 20-30%), while maintaining the latter approach in MRD+ cases and very HR subsets.

The prognostic role of MRD evaluation in unselected patients will be evaluated.

Being tested
Postremission consolidation based on MRD status
Keywords
Acute lymphoblastic leukemia, Adult patients, Minimal residual disease, Risk-oriented therapy
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neoplasm, Residual

What participants receive

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

  • Postremission consolidation based on MRD statusBehavioural

    Also called MRD-guided therapy

    Application of combination chemotherapy aimed to reduce MRD burden in unselected patients, followed by MRD-adjusted therapy that range from maintenance chemotherapy (MRD-negative patients) to allogeneic SCT (MRD-positive patients) or high-dose therapy with autologous blood stem cell support (MRD-positive patients without compatible donor for allogeneic SCT)

Study groups in NCT00358072
Study groupRoleWhat they receive
1ExperimentalApplication of combination chemotherapy aimed to reduce MRD burden in unselected patients, followed by MRD-adjusted therapy that range from maintenance chemotherapy (MRD-negative patients) to allogeneic SCT (MRD-positive patients) or high-dose therapy with autologous blood stem cell support (MRD-positive patients without compatible donor for allogeneic SCT)
Receives: Behavioral: Postremission consolidation based on MRD status

What is being measured

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

  1. Disease-free survival at 5 years

    Measured: 5 year from date of complete remission

Secondary outcomes (5)

  1. Complete remission

    Measured: 4 or 8 weeks from date of therapy start

  2. Overall survival

    Measured: 5 years from date of diagnosis

  3. Cumulative incidence of relpase

    Measured: 5 years from date of complete remission

  4. Remissional deaths

    Measured: 4 weeks from date of therapy start

  5. Nonlethal toxicity

    Measured: 5 years from date of therapy start

Timeline

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

  1. First posted28 Jul 2006 (estimated)
  2. Study startMay 2000
  3. Primary completionDec 2006
  4. Study completionSep 2008

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
280 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00358072
Sponsor's protocol ID
NILG-ALL 09/00
Status last verified
Dec 2010
First submitted
26 Jul 2006
Last updated
29 Dec 2010
Results posted
No
Data monitoring committee
No

Publications

  • Bassan R, Spinelli O, Oldani e et al. Minimal residual disease (MRD) and risk-oriented therapy in adult acute lymhoblastic leukemia (ALL). Blood (ASH Annual Meeting Abstract) 106: abstract 1836, 2005.

  • Bassan R, Spinelli O, Oldani E, Intermesoli T, Tosi M, Peruta B, Rossi G, Borlenghi E, Pogliani EM, Terruzzi E, Fabris P, Cassibba V, Lambertenghi-Deliliers G, Cortelezzi A, Bosi A, Gianfaldoni G, Ciceri F, Bernardi M, Gallamini A, Mattei D, Di Bona E, Romani C, Scattolin AM, Barbui T, Rambaldi A. Improved risk classification for risk-specific therapy based on the molecular study of minimal residual disease (MRD) in adult acute lymphoblastic leukemia (ALL). Blood. 2009 Apr 30;113(18):4153-62. doi: 10.1182/blood-2008-11-185132. Epub 2009 Jan 13.

    PubMed 19141862

  • Bassan R, Rossi G, Pogliani EM, Di Bona E, Angelucci E, Cavattoni I, Lambertenghi-Deliliers G, Mannelli F, Levis A, Ciceri F, Mattei D, Borlenghi E, Terruzzi E, Borghero C, Romani C, Spinelli O, Tosi M, Oldani E, Intermesoli T, Rambaldi A. Chemotherapy-phased imatinib pulses improve long-term outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: Northern Italy Leukemia Group protocol 09/00. J Clin Oncol. 2010 Aug 1;28(22):3644-52. doi: 10.1200/JCO.2010.28.1287. Epub 2010 Jul 6.

    PubMed 20606084

  • Mannelli F, Gianfaldoni G, Intermesoli T, Cattaneo C, Borlenghi E, Cortelazzo S, Cavattoni I, Pogliani EM, Fumagalli M, Angelucci E, Romani C, Ciceri F, Corti C, Scattolin A, Cortelezzi A, Mattei D, Audisio E, Spinelli O, Oldani E, Bosi A, Rambaldi A, Bassan R. CD20 expression has no prognostic role in Philadelphia-negative B-precursor acute lymphoblastic leukemia: new insights from the molecular study of minimal residual disease. Haematologica. 2012 Apr;97(4):568-71. doi: 10.3324/haematol.2011.054064. Epub 2011 Nov 4.

    PubMed 22058217

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Postremission consolidation based on MRD status in people with Acute Lymphoblastic Leukemia, run by Northern Italy Leukemia Group at 15 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 3 inclusion and 1 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 29 Dec 2010. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 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?

Disease-free survival at 5 years (time frame: 5 year from date of complete remission). 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 NCT00358072, which also lists 4 linked publications.

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 29 Dec 2010.

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