Treatment of Adult ALL With an MRD-directed Programme.
- Conditions
- Acute Lymphoblastic Leukemia
- Interventions
- Behavioral: Postremission consolidation based on MRD status
- Registration Number
- NCT00358072
- Lead Sponsor
- Northern Italy Leukemia Group
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 280
- 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
- Any co-morbidity precluding the administration of intensive chemotherapy for adult ALL
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 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)
- Primary Outcome Measures
Name Time Method Disease-free survival at 5 years 5 year from date of complete remission
- Secondary Outcome Measures
Name Time Method Nonlethal toxicity 5 years from date of therapy start Complete remission 4 or 8 weeks from date of therapy start Overall survival 5 years from date of diagnosis Cumulative incidence of relpase 5 years from date of complete remission Remissional deaths 4 weeks from date of therapy start
Trial Locations
- Locations (15)
Ospedali Riuniti di Bergamo
🇮🇹Bergamo, BG, Italy
Ematologia Centro TMO Fondazione IRCSS Ospedale Maggiore
🇮🇹Milano, MI, Italy
Divisione Ematologia Spedali Civili
🇮🇹Brescia, BS, Italy
U.O. Ematologia e Centro TMO Ospedale Armando Businco
🇮🇹Cagliari, CA, Italy
Ematologia Azienda Ospedaliera S.Croce e Carle
🇮🇹Cuneo, CN, Italy
U.S. Ematologia - Centro TMO Istituti Ospedalieri
🇮🇹Cremona, CR, Italy
Ematologia AOU Careggi
🇮🇹Firenze, FI, Italy
Ematologia - TMO Ospedale San Gerardo
🇮🇹Monza, MI, Italy
Ematologia e TMO Ospedale San Raffaele
🇮🇹Milano, MI, Italy
Divisione di Ematologia e TMO Ospedale San Maurizio
🇮🇹Bolzano, BZ, Italy
Divisione Ematologia Ospedale Umberto I
🇮🇹Mestre, VE, Italy
Ematologia 2 Ospedale San Giovanni Battista
🇮🇹Torino, TO, Italy
Oncoematologia e TMO Dipartimento Oncologico
🇮🇹Palermo, PA, Italy
Oncologia ed Ematologia Oncologica Institution Regione Veneto, ULSS n.13 - Presidi Ospedalieri di Noale, Mirano, Dolo
🇮🇹Noale, VE, Italy
Ematologia Ospedale San Bortolo
🇮🇹Vicenza, VI, Italy