Treatment Protocol for Relapsed Acute Promyelocytic Leukemia (APL) With Arsenic
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00196768|
Recruitment Status : Unknown
Verified October 2007 by German AML Cooperative Group.
Recruitment status was: Recruiting
First Posted : September 20, 2005
Last Update Posted : October 23, 2007
|First Submitted Date ICMJE||September 12, 2005|
|First Posted Date ICMJE||September 20, 2005|
|Last Update Posted Date||October 23, 2007|
|Study Start Date ICMJE||January 2005|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE
|Change History||Complete list of historical versions of study NCT00196768 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Treatment Protocol for Relapsed Acute Promyelocytic Leukemia (APL) With Arsenic|
|Official Title ICMJE||Treatment of Relapsed Acute Promyelocytic Leukemia With Arsenic Trioxide (Phase IV Study)|
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:
Induction therapy with ATO is the mandatory part of the protocol.
After remission induction, there are several options for postremission therapy. Factors which have influence on the treatment decision in the individual case are:
A mandatory form of post-remission therapy is not defined in the protocol. Data and outcomes of any post-remission therapy should be documented in order to collect data of treatment after ATO.
The following stratification of post-remission therapy can be performed according to the decision of the treating physician:
Patients with a HLA-compatible donor who are suitable for allogeneic stem cell transplantation should be transplanted. In patients with a positive PCR one cycle of intensive chemotherapy (HAM) before transplantation should be considered and patients with a negative result are immediately transplanted without preceding chemotherapy. In patients who do not qualify for allogeneic, but for autologous transplantation, the intensity of the chemotherapy (Ara-C dose of the HAM cycle) is scheduled according to the PCR status after ATO and to the patient's age. In patients under 60 years, the recommended single Ara-C dose is scheduled to 3 g/m² in case of a positive PCR result and to 1 g/m² in case of a negative PCR result after ATO. In all patients aged over 60 years, the Ara-C dose should be uniformly reduced to 1 g/m² independent of the PCR status. Patients who are not eligible for allogeneic or autologous transplantation (too old, no stem cells collected, PCR positive stem cell transplant, contraindications against intensive chemotherapy) receive three further cycles with ATO and ATRA. The group of patients not qualifying for autologous transplantation, but without contraindications against intensive chemotherapy should receive an age adapted HAM, whenever a positive PCR persists or reappears after the three maintenance cycles of ATO. A close monitoring of the PCR of PML/RARa after each treatment cycle is part of the protocol.
The main objective of the protocol is to take advantage of the expected low toxicity of ATO and to keep the part of chemotherapy as low as possible.
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
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 4|
|Study Design ICMJE||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Study Arms ICMJE||Not Provided|
|Publications *||Toft P, Olsen HT, Jørgensen HK, Strøm T, Nibro HL, Oxlund J, Wian KA, Ytrebø LM, Kroken BA, Chew M. Non-sedation versus sedation with a daily wake-up trial in critically ill patients receiving mechanical ventilation (NONSEDA Trial): study protocol for a randomised controlled trial. Trials. 2014 Dec 20;15:499. doi: 10.1186/1745-6215-15-499.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Unknown status|
|Estimated Enrollment ICMJE
|Original Enrollment ICMJE||Same as current|
|Study Completion Date ICMJE||December 2010|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages ICMJE||18 Years and older (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||Germany|
|Removed Location Countries|
|NCT Number ICMJE||NCT00196768|
|Other Study ID Numbers ICMJE||30052004|
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||German AML Cooperative Group|
|Collaborators ICMJE||Not Provided|
|PRS Account||German AML Cooperative Group|
|Verification Date||October 2007|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP