Trial record 1 of 127 for:    ACUTE PROMYELOCYTIC LEUKEMIA
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Treatment Protocol for Relapsed Acute Promyelocytic Leukemia (APL) With Arsenic

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2007 by German AML Cooperative Group.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
German AML Cooperative Group
ClinicalTrials.gov Identifier:
NCT00196768
First received: September 12, 2005
Last updated: October 22, 2007
Last verified: October 2007
  Purpose

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 Intervention Phase
Relapsed Acute Promyelocytic Leukemia
Refractory Acute Promyelocytic Leukemia
Drug: Arsenic trioxide
Drug: Trisenox
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Relapsed Acute Promyelocytic Leukemia With Arsenic Trioxide (Phase IV Study)

Resource links provided by NLM:


Further study details as provided by German AML Cooperative Group:

Primary Outcome Measures:
  • the rate of hematological remission
  • the rate of molecular remission
  • the kinetics of the MRD of PML/RARa during and after ATO

Secondary Outcome Measures:
  • 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

Estimated Enrollment: 30
Study Start Date: January 2005
Estimated Study Completion Date: December 2010
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00196768

Contacts
Contact: Eva Lengfelder, MD, PhD 0049 621 3834110 eva.lengfelder@med3.ma.uni-heidelberg.de

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

No publications provided

ClinicalTrials.gov Identifier: NCT00196768     History of Changes
Other Study ID Numbers: 30052004
Study First Received: September 12, 2005
Last Updated: October 22, 2007
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by German AML Cooperative Group:
relapsed
acute promyelocytic leukemia
arsenic

Additional relevant MeSH terms:
Leukemia
Leukemia, Promyelocytic, Acute
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Arsenic trioxide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 21, 2014