Treatment of Adult ALL With an MRD-directed Programme.

NCT ID: NCT00358072

Last Updated: 2010-12-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

280 participants

Study Classification

INTERVENTIONAL

Study Start Date

2000-05-31

Study Completion Date

2008-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Acute Lymphoblastic Leukemia

Keywords

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Acute lymphoblastic leukemia Adult patients Minimal residual disease Risk-oriented therapy

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

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)

Group Type EXPERIMENTAL

Postremission consolidation based on MRD status

Intervention Type BEHAVIORAL

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)

Interventions

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Postremission consolidation based on MRD status

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)

Intervention Type BEHAVIORAL

Other Intervention Names

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MRD-guided therapy

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* Any co-morbidity precluding the administration of intensive chemotherapy for adult ALL
Minimum Eligible Age

15 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Associazione Italiana per la Ricerca sul Cancro

OTHER

Sponsor Role collaborator

Northern Italy Leukemia Group

OTHER

Sponsor Role lead

Responsible Party

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Ospedali Riuniti, Div. Ematologia, Bergamo, Italy

Principal Investigators

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Bassan Renato, MD

Role: PRINCIPAL_INVESTIGATOR

Azienda Ospedaliera Ospedali Riuniti di Bergamo

Locations

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Ospedali Riuniti di Bergamo

Bergamo, BG, Italy

Site Status

Divisione Ematologia Spedali Civili

Brescia, BS, Italy

Site Status

Divisione di Ematologia e TMO Ospedale San Maurizio

Bolzano, BZ, Italy

Site Status

U.O. Ematologia e Centro TMO Ospedale Armando Businco

Cagliari, CA, Italy

Site Status

Ematologia Azienda Ospedaliera S.Croce e Carle

Cuneo, CN, Italy

Site Status

U.S. Ematologia - Centro TMO Istituti Ospedalieri

Cremona, CR, Italy

Site Status

Ematologia AOU Careggi

Florence, FI, Italy

Site Status

Ematologia Centro TMO Fondazione IRCSS Ospedale Maggiore

Milan, MI, Italy

Site Status

Ematologia e TMO Ospedale San Raffaele

Milan, MI, Italy

Site Status

Ematologia - TMO Ospedale San Gerardo

Monza, MI, Italy

Site Status

Oncoematologia e TMO Dipartimento Oncologico

Palermo, PA, Italy

Site Status

Ematologia 2 Ospedale San Giovanni Battista

Torino, TO, Italy

Site Status

Divisione Ematologia Ospedale Umberto I

Mestre, VE, Italy

Site Status

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

Noale, VE, Italy

Site Status

Ematologia Ospedale San Bortolo

Vicenza, VI, Italy

Site Status

Countries

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Italy

References

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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.

Reference Type RESULT

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.

Reference Type RESULT
PMID: 19141862 (View on PubMed)

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.

Reference Type RESULT
PMID: 20606084 (View on PubMed)

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.

Reference Type DERIVED
PMID: 22058217 (View on PubMed)

Other Identifiers

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NILG-ALL 09/00

Identifier Type: -

Identifier Source: org_study_id