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Treatment of Adult ALL With an MRD-directed Programme.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00358072
Recruitment Status : Completed
First Posted : July 28, 2006
Last Update Posted : December 29, 2010
Sponsor:
Collaborator:
Associazione Italiana per la Ricerca sul Cancro
Information provided by:
Northern Italy Leukemia Group

Study Description
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Brief 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 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.


Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Behavioral: Postremission consolidation based on MRD status Phase 2

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 280 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Study Start Date : May 2000
Actual Primary Completion Date : December 2006
Actual Study Completion Date : September 2008

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 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)
 Behavioral: 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)
Other Name: MRD-guided therapy


Outcome Measures
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Primary Outcome Measures :
  1. Disease-free survival at 5 years [ Time Frame: 5 year from date of complete remission ]

Secondary Outcome Measures :
  1. Complete remission [ Time Frame: 4 or 8 weeks from date of therapy start ]
  2. Overall survival [ Time Frame: 5 years from date of diagnosis ]
  3. Cumulative incidence of relpase [ Time Frame: 5 years from date of complete remission ]
  4. Remissional deaths [ Time Frame: 4 weeks from date of therapy start ]
  5. Nonlethal toxicity [ Time Frame: 5 years from date of therapy start ]

Eligibility Criteria
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Ages Eligible for Study:   15 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00358072


Locations
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Italy
Ospedali Riuniti di Bergamo
Bergamo, BG, Italy, 24128
Divisione Ematologia Spedali Civili
Brescia, BS, Italy, 25123
Divisione di Ematologia e TMO Ospedale San Maurizio
Bolzano, BZ, Italy, 39100
U.O. Ematologia e Centro TMO Ospedale Armando Businco
Cagliari, CA, Italy, 09121
Ematologia Azienda Ospedaliera S.Croce e Carle
Cuneo, CN, Italy, 12100
U.S. Ematologia - Centro TMO Istituti Ospedalieri
Cremona, CR, Italy, 26100
Ematologia AOU Careggi
Firenze, FI, Italy, 50134
Ematologia Centro TMO Fondazione IRCSS Ospedale Maggiore
Milano, MI, Italy, 20122
Ematologia e TMO Ospedale San Raffaele
Milano, MI, Italy, 20132
Ematologia - TMO Ospedale San Gerardo
Monza, MI, Italy, 20052
Oncoematologia e TMO Dipartimento Oncologico
Palermo, PA, Italy, 90146
Ematologia 2 Ospedale San Giovanni Battista
Torino, TO, Italy, 10126
Divisione Ematologia Ospedale Umberto I
Mestre, VE, Italy, 30172
Oncologia ed Ematologia Oncologica Institution Regione Veneto, ULSS n.13 - Presidi Ospedalieri di Noale, Mirano, Dolo
Noale, VE, Italy, 30033
Ematologia Ospedale San Bortolo
Vicenza, VI, Italy, 36100
Sponsors and Collaborators
Northern Italy Leukemia Group
Associazione Italiana per la Ricerca sul Cancro
Investigators
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Principal Investigator: Bassan Renato, MD Azienda Ospedaliera Ospedali Riuniti di Bergamo
More Information
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Publications of Results:
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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Renato Bassan, MD, Ospedali Riuniti, Div. Ematologia, Bergamo, Italy
ClinicalTrials.gov Identifier: NCT00358072    
Other Study ID Numbers: NILG-ALL 09/00
First Posted: July 28, 2006    Key Record Dates
Last Update Posted: December 29, 2010
Last Verified: December 2010
Keywords provided by Northern Italy Leukemia Group:
Acute lymphoblastic leukemia
Adult patients
Minimal residual disease
Risk-oriented therapy
Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
 Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases