Clinical Trial: Treatment Protocol for Relapsed Acute Promyelocytic Leukemia (APL) With Arsenic
Study Status: Recruiting
Recruit Status: Unknown status
Study Type: Interventional
Official Title: Treatment of Relapsed Acute Promyelocytic Leukemia With Arsenic Trioxide (Phase IV Study)
Brief Summary:
Summary
Acute promyelocytic leukemia is defined by a characteristic morphology (AML FAB M3/M3v), by the specific translocation t(15;17) and its molecular correlates (PML/RARa and RARa/PML). Thereby it can be separated from all other forms of acute leukemia.
By all-trans retinoic acid in combination with chemotherapy cure rates of 70 to 80% can be reached. On average, about 10% of patients still die in the early phase of the treatment and about 20 to 30% relapse. Molecular monitoring of the minimal residual disease (MRD) by qualitative nested RT-PCR and quantitative REAL-time PCR of PML/RARa allows to follow the individual kinetics of MRD and to identify patients with an imminent hematological relapse.
A standardized treatment for patients with relapsed APL has not yet been established. With arsenic trioxide (ATO) monotherapy remission rates over 80% were achieved and long-lasting molecular remissions are described. The drug was mostly well tolerated. ATO exerts a dose dependent dual effect on APL blasts, apoptosis in higher and partial differentiation in lower concentrations. ATO was also successfully administered before allogeneic and autologous transplantation. ATO is approved for the treatment of relapsed and refractory APL in Europe and in the USA.
In the present protocol, ATO is given for remission induction:
- in patients with hematological or molecular first or subsequent relapse of APL and
- in patients who do not reach a hematological or molecular remission after first line therapy.
Induction therapy with ATO is the mandatory part of the protocol.
Detailed Summary:
Synopsis
Title of study
Treatment of acute promyelocytic leukemia (APL) with arsenic trioxide (ATO). A phase-IV study to assess the effectiveness and toxicity of ATO as well as the kinetics of minimal residual disease (MRD) in patients with first and subsequent hematological or molecular relapse of APL.
Study coordination: Priv.-Doz. Dr. Eva Lengfelder
Protocol committee: German AMLCG and German AML-Intergroup (open for other participating groups)
Study duration: Time of recruitment 3 years, individual follow up scheduled for 3 years
Objectives of the study
Primary objectives
Assessment of:
- the rate of hematological remission
- the rate of molecular remission
- the kinetics of the MRD of PML/RARa during and after ATO
Secondary objectives
Assessment of:
- the side effects of ATO
- percentage of transplantable patients in comparison to the historical results after chemotherapy
- the overall survival
-
duration of the hematological and molecular remission
Study characteristics: Open-label multicenter controlled
Sponsor: German AML Cooperative Group
Current Primary Outcome:
- the rate of hematological remission
- the rate of molecular remission
- the kinetics of the MRD of PML/RARa during and after ATO
Original Primary Outcome:
- Assessment of
- 1) the rate of hematological remission
- 2) the rate of molecular remission
- 3) the kinetics of the MRD of PML/RARa during and after ATO
Current Secondary Outcome:
- the side effects of ATO
- percentage of transplantable patients in comparison to the historical results after chemotherapy
- the overall survival
- duration of the hematological and molecular remission
Original Secondary Outcome:
- Secondary objectives
- Assessment of
- 1) the side effects of ATO
- 2) percentage of transplantable patients in comparison to the historical results after chemotherapy
- 3) the overall survival
- 4) duration of the hematological and molecular remission
Information By: German AML Cooperative Group
Dates:
Date Received: September 12, 2005
Date Started: January 2005
Date Completion: December 2010
Last Updated: October 22, 2007
Last Verified: October 2007
