Treatment of Adult ALL With an MRD-directed Programme.

This study has been completed.
Sponsor:
Collaborator:
Associazione Italiana per la Ricerca sul Cancro
Information provided by:
Northern Italy Leukemia Group
ClinicalTrials.gov Identifier:
NCT00358072
First received: July 26, 2006
Last updated: December 28, 2010
Last verified: December 2010
  Purpose

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 Intervention Phase
Acute Lymphoblastic Leukemia
Behavioral: Postremission consolidation based on MRD status
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by Northern Italy Leukemia Group:

Primary Outcome Measures:
  • Disease-free survival at 5 years [ Time Frame: 5 year from date of complete remission ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete remission [ Time Frame: 4 or 8 weeks from date of therapy start ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 5 years from date of diagnosis ] [ Designated as safety issue: No ]
  • Cumulative incidence of relpase [ Time Frame: 5 years from date of complete remission ] [ Designated as safety issue: No ]
  • Remissional deaths [ Time Frame: 4 weeks from date of therapy start ] [ Designated as safety issue: Yes ]
  • Nonlethal toxicity [ Time Frame: 5 years from date of therapy start ] [ Designated as safety issue: Yes ]

Enrollment: 280
Study Start Date: May 2000
Study Completion Date: September 2008
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   15 Years to 65 Years
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00358072

Locations
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
Principal Investigator: Bassan Renato, MD Azienda Ospedaliera Ospedali Riuniti di Bergamo
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Renato Bassan, MD, Ospedali Riuniti, Div. Ematologia, Bergamo, Italy
ClinicalTrials.gov Identifier: NCT00358072     History of Changes
Other Study ID Numbers: NILG-ALL 09/00
Study First Received: July 26, 2006
Last Updated: December 28, 2010
Health Authority: Italy: Ministry of Health

Keywords provided by Northern Italy Leukemia Group:
Acute lymphoblastic leukemia
Adult patients
Minimal residual disease
Risk-oriented therapy

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasm, Residual
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplastic Processes
Pathologic Processes

ClinicalTrials.gov processed this record on April 17, 2014