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Treatment of Adult ALL With an MRD-directed Programme.

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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

Tracking Information
First Submitted Date  ICMJE July 26, 2006
First Posted Date  ICMJE July 28, 2006
Last Update Posted Date December 29, 2010
Study Start Date  ICMJE May 2000
Actual Primary Completion Date December 2006   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 28, 2010)
Disease-free survival at 5 years [ Time Frame: 5 year from date of complete remission ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 26, 2006)
Disease-free survival at 5 years
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 28, 2010)
  • Complete remission [ Time Frame: 4 or 8 weeks from date of therapy start ]
  • Overall survival [ Time Frame: 5 years from date of diagnosis ]
  • Cumulative incidence of relpase [ Time Frame: 5 years from date of complete remission ]
  • Remissional deaths [ Time Frame: 4 weeks from date of therapy start ]
  • Nonlethal toxicity [ Time Frame: 5 years from date of therapy start ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 26, 2006)
  • Complete remission
  • Overall survival
  • Cumulative incidence of relpase
  • Remissional deaths
  • Nonlethal toxicity
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Treatment of Adult ALL With an MRD-directed Programme.
Official Title  ICMJE 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.
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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Lymphoblastic Leukemia
Intervention  ICMJE 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
Study Arms  ICMJE 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)
Intervention: Behavioral: Postremission consolidation based on MRD status
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 28, 2010)
280
Original Enrollment  ICMJE
 (submitted: July 26, 2006)
250
Actual Study Completion Date  ICMJE September 2008
Actual Primary Completion Date December 2006   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 15 Years to 65 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00358072
Other Study ID Numbers  ICMJE NILG-ALL 09/00
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Renato Bassan, MD, Ospedali Riuniti, Div. Ematologia, Bergamo, Italy
Study Sponsor  ICMJE Northern Italy Leukemia Group
Collaborators  ICMJE Associazione Italiana per la Ricerca sul Cancro
Investigators  ICMJE
Principal Investigator: Bassan Renato, MD Azienda Ospedaliera Ospedali Riuniti di Bergamo
PRS Account Northern Italy Leukemia Group
Verification Date December 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP