Treatment of Adult ALL With an MRD-directed Programme.

December 28, 2010 updated by: Northern Italy Leukemia Group

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

280

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • BG
      • Bergamo, BG, Italy, 24128
        • Ospedali Riuniti di Bergamo
    • BS
      • Brescia, BS, Italy, 25123
        • Divisione Ematologia Spedali Civili
    • BZ
      • Bolzano, BZ, Italy, 39100
        • Divisione di Ematologia e TMO Ospedale San Maurizio
    • CA
      • Cagliari, CA, Italy, 09121
        • U.O. Ematologia e Centro TMO Ospedale Armando Businco
    • CN
      • Cuneo, CN, Italy, 12100
        • Ematologia Azienda Ospedaliera S.Croce e Carle
    • CR
      • Cremona, CR, Italy, 26100
        • U.S. Ematologia - Centro TMO Istituti Ospedalieri
    • FI
      • Firenze, FI, Italy, 50134
        • Ematologia AOU Careggi
    • MI
      • Milano, MI, Italy, 20132
        • Ematologia e TMO Ospedale San Raffaele
      • Milano, MI, Italy, 20122
        • Ematologia Centro TMO Fondazione IRCSS Ospedale Maggiore
      • Monza, MI, Italy, 20052
        • Ematologia - TMO Ospedale San Gerardo
    • PA
      • Palermo, PA, Italy, 90146
        • Oncoematologia e TMO Dipartimento Oncologico
    • TO
      • Torino, TO, Italy, 10126
        • Ematologia 2 Ospedale San Giovanni Battista
    • VE
      • Mestre, VE, Italy, 30172
        • Divisione Ematologia Ospedale Umberto I
      • Noale, VE, Italy, 30033
        • Oncologia ed Ematologia Oncologica Institution Regione Veneto, ULSS n.13 - Presidi Ospedalieri di Noale, Mirano, Dolo
    • VI
      • Vicenza, VI, Italy, 36100
        • Ematologia Ospedale San Bortolo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • MRD-guided therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Disease-free survival at 5 years
Time Frame: 5 year from date of complete remission
5 year from date of complete remission

Secondary Outcome Measures

Outcome Measure
Time Frame
Complete remission
Time Frame: 4 or 8 weeks from date of therapy start
4 or 8 weeks from date of therapy start
Overall survival
Time Frame: 5 years from date of diagnosis
5 years from date of diagnosis
Cumulative incidence of relpase
Time Frame: 5 years from date of complete remission
5 years from date of complete remission
Remissional deaths
Time Frame: 4 weeks from date of therapy start
4 weeks from date of therapy start
Nonlethal toxicity
Time Frame: 5 years from date of therapy start
5 years from date of therapy start

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northern Italy Leukemia Group

Collaborators

Associazione Italiana per la Ricerca sul Cancro

Investigators

  • Principal Investigator: Bassan Renato, MD, Azienda Ospedaliera Ospedali Riuniti di Bergamo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2000

Primary Completion (Actual)

December 1, 2006

Study Completion (Actual)

September 1, 2008

Study Registration Dates

First Submitted

July 26, 2006

First Submitted That Met QC Criteria

July 26, 2006

First Posted (Estimate)

July 28, 2006

Study Record Updates

Last Update Posted (Estimate)

December 29, 2010

Last Update Submitted That Met QC Criteria

December 28, 2010

Last Verified

December 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NILG-ALL 09/00

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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