Optimization of Therapy in Adult Patients With Newly Diagnosed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma by Individualised, Targeted and Intensified Treatment

Sponsor
Goethe University
Study ID
NCT02881086
Phase
PHASE3
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 55 Years
Healthy Volunteers
Not accepted

Interventions

  • Rituximab — DRUG
  • Nelarabine — DRUG
  • PEG-Asparaginase — DRUG
  • Cranial irradiation — PROCEDURE
  • Imatinib — DRUG
  • Idarubicin — DRUG
  • Dexamethasone — DRUG
  • Cyclophosphamide — DRUG
  • Fludarabine — DRUG
  • Vincristine — DRUG
  • Mercaptopurine — DRUG
  • VP16 — DRUG
  • Daunorubicin (DNR) — DRUG
  • Methotrexate — DRUG
  • Stem cell transplantation — PROCEDURE
  • Cytarabine — DRUG
  • Vindesine — DRUG
  • Adriamycin — DRUG
  • Prednisolone — DRUG

Study Details

A phase IV study with the primary goal to optimize therapy of adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma (LBL) by dose and time intensive, pediatric based chemotherapy, risk adapted stem cell transplantation (SCT) and minimal residual disease (MRD) based individualised and intensified therapy. Study will further evaluate the role of asparaginase intensification, the extended use of rituximab and the use of nelarabine as consolidation therapy in T-ALL in a phase III-part of the study. Furthermore two randomisations will focus on the role of central nervous system (CNS) irradiation in combination with intrathecal therapy versus intrathecal therapy only in B-precursor ALL/LBL and the role of SCT in high-risk patients with molecular complete remission. Finally a new, dose reduced induction therapy in combination with Imatinib will be evaluated in Ph/BCR-ABL positive ALL.

Key Dates

Start date
Aug 31, 2016
Status verified
Dec 2025
Primary completion
Dec 31, 2024
Completion
Dec 31, 2024

Study Design

Enrollment
1,023 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Other: Stratification I - Standard Risk (SR)/ High Risk (HR)
    Induction and consolidation I therapy for standard and high risk patients, PH/BCR-ABL-negative Chemotherapy, immunotherapy, intrathecal prophylaxis, CNS irradiation according to randomisation I Drugs: Rituximab, Vincristine, Daunorubicin, Dexamethasone, Cyclophosphamide, Cytarabine, Mercaptopurine, PEG-Asparaginase, Methotrexate, Vindesine, VP16
  • Other: Stratification I - Philadelphia (PH)+
    Induction and consolidation I therapy for PH+ patients Chemotherapy, immunotherapy, intrathecal prophylaxis Drugs: Rituximab, Vincristine, Imatinib, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, VP16
  • Active Comparator: Rand I - B-Lin + CNS Rad + i.th. MTX
    Chemotherapy according to Stratification I SR/HR CNS prophylaxis: CNS irradiation 24 Gy, intrathecal Methotrexate
  • Experimental: Rand I - B-Lin + i.th. MTX
    Chemotherapy according to Stratification I SR/HR CNS prophylaxis: intrathecal Methotrexate
  • Other: Stratification II - SR + MRD-neg
    Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine, Dexamethasone
  • Other: Stratification II - HR + MRD-neg
    Chemotherapy or stem cell transplantation according to randomisation II
  • Other: Stratification II - SR/HR/PH+ + MRD-pos
    Chemotherapy or targeted therapy, followed by stem cell transplantation Drugs: Fludarabine, Idarubicin, Cytarabine, Nelarabine
  • Active Comparator: Randomisation II - HR + MRD-neg-SCT
    Stem cell transplantation
  • Experimental: Randomisation II - HR + MRD-neg-SR-chemo
    Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine

Primary Outcome Measure

Event free survival [ Time Frame: 3.5 years ]

Related Studies