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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. 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
Information provided by:
German AML Cooperative Group

Brief 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:

  1. in patients with hematological or molecular first or subsequent relapse of APL and
  2. 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.

After remission induction, there are several options for postremission therapy. Factors which have influence on the treatment decision in the individual case are:

  1. the eligibility for allogeneic transplantation
  2. the eligibility for autologous transplantation
  3. the presence or absence of contraindications against intensive chemotherapy
  4. the PCR status after induction and during follow up (RT-PCR of PML/RARa, sensitivity 10-4)

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.

Condition or disease Intervention/treatment Phase
Relapsed Acute Promyelocytic Leukemia Refractory Acute Promyelocytic Leukemia Drug: Arsenic trioxide Drug: Trisenox Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Relapsed Acute Promyelocytic Leukemia With Arsenic Trioxide (Phase IV Study)
Study Start Date : January 2005
Study Completion Date : December 2010

Primary Outcome Measures :
  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

Secondary Outcome Measures :
  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

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients in first or subsequent hematological or molecular relapse of APL
  • Persistence of a positive PCR or no hematological complete remission (CR) after first line therapy
  • No complete hematological remission after first line therapy
  • Age over 18 years
  • No upper age limit
  • Informed consent of the patient

Exclusion Criteria:

  • Absolute QTc-interval prolonged over 460 msec before therapy (normal electrolytes, no other drugs prolonging the QT-interval)
  • Heart failure New York Health Association grade III and IV
  • Renal or hepatic failure World Health Organization grade >= III
  • Pneumonia with hypoxemia
  • Uncontrolled sepsis
  • Pregnancy and lactation period
  • Secondary malignancy, which will have major influence on the prognosis
  • Expected noncompliance
  • No informed consent of the patient.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00196768

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Contact: Eva Lengfelder, MD, PhD 0049 621 3834110

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Eva Lengfelder, MD, PhD Recruiting
Mannheim, Germany, 68305
Principal Investigator: Eva Lengfelder, MD, PhD         
Sponsors and Collaborators
German AML Cooperative Group
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Principal Investigator: Eva Lengfelder, MD, PhD German AMLCG

Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information Identifier: NCT00196768     History of Changes
Other Study ID Numbers: 30052004
First Posted: September 20, 2005    Key Record Dates
Last Update Posted: October 23, 2007
Last Verified: October 2007
Keywords provided by German AML Cooperative Group:
acute promyelocytic leukemia
Additional relevant MeSH terms:
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Leukemia, Promyelocytic, Acute
Neoplasms by Histologic Type
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Arsenic Trioxide
Antineoplastic Agents