Clinical Trial: Study for Patients With Newly Diagnosed, High-risk Acute Promyelocytic Leukemia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Randomized Phase III Study to Compare Arsenic Trioxide (ATO) Combined to ATRA and Idarubicin Versus Standard ATRA and Anthracyclines-based Chemotherapy (AIDA Regimen) for Patients With Newly Diagnos

Brief Summary:

Acute promyelocytic leukemia (APL) is a rare subtype of acute myeloid leukemia (AML) characterized by consistent clinical, morphologic, and genetic features. According to the FAB classification APL is designated as"M3 leukemia" and assigned to the WHO defined type of AML with recurrent cytogenetic abnormalities, "acute promyelocytic leukemia with t(15;17)(q22;q12), (PML/RARα) and variants".

Despite the dramatic progress achieved in frontline therapy of APL with ATRA plus anthracycline-based regimens, relapses still occur in approximately 20% of patients. Moreover, these regimens are associated with significant toxicities due to severe myelosuppression frequently associated with life-threatening infections and potentially serious late effects including development of secondary MDS/AML. In a recent randomized clinical trial in low/intermediate-risk APL (WBC ≤ 10 GPt/l APL0406 trial) a combination of arsenic trioxide (ATO) and ATRA has been shown to result into better survival with significantly lower toxicity rates compared to the standard ATRA + idarubicin (AIDA) therapy. Inspired by the results of this trial the investigators intend to perform a randomized study in high-risk APL (WBC at diagnosis > 10 GPt/l) comparing standard AIDA-based treatment with ATO/ATRA combination including low-doses idarubicin during induction. The investigators propose a modified ATO/ATRA protocol with the addition of two doses of IDA (50% compared to standard AIDA induction) for induction because of the anticipated need of adding anthracyclines to control hyperleukocytosis and to achieve long-term disease control in this high-risk APL population. This is followed by 4 cycles of ATO/ATRA consolidation therapy. As in the APL0406 study for low/intermediate-risk patients the investigators expect less severe hematologic toxicity and treatment-related mortality resu

Detailed Summary:
Sponsor: Technische Universität Dresden

Current Primary Outcome: Event-free survival [ Time Frame: From date of randomization until the date of first documented event, assessed up to 66 months ]

events are: no achievement of haematological complete remission after induction therapy; no achievement of molecular remission after the last consolidation course; relapse; death including early death or development of secondary AML or MDS


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Rate of hematological complete remission [ Time Frame: up to 60 days, from date of randomization until end of induction therapy ]
  • Rate of early death within 30 days after randomization [ Time Frame: up to 30 days after randomization ]
  • Rate of overall survival (OS) [ Time Frame: at 2 years ]
  • Rate of cumulative incidence of secondary MDS or AML [ Time Frame: assessed up to 66 months, from date of randomization until occurance of secondary AML or MDS ]
  • Rate of cumulative incidence of relapse (CIR) [ Time Frame: at 2 years ]
  • Incidence of hematological and non-hematological toxicity [ Time Frame: assessed up to 30 months after randomization ]
  • Rate of molecular remission after the last consolidation cycle [ Time Frame: up to 256 days after randomization ]
  • Assessment of acute promyelocytic leukemia/RARa transcript level reduction after induction therapy until end of study [ Time Frame: assessed up to 30 months after randomization ]
  • Quality of Life at the end of induction therapy until the end of study [ Time Frame: assessed up to 30 months after randomization ]
  • To investigate differences in the immune reconstitution between the two arms [ Time Frame: assessed up to 30 months after randomization ]
  • Total hospitalization days during therapy [ Time Frame: assessed up to 30 months after randomization ]


Original Secondary Outcome: Same as current

Information By: Technische Universität Dresden

Dates:
Date Received: February 11, 2016
Date Started: June 2016
Date Completion: January 2022
Last Updated: July 7, 2016
Last Verified: July 2016