Treatment of Relapsed Promyelocytic Leukemia With Arsenic Trioxide (ATO)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by PETHEMA Foundation
Sponsor:
Information provided by (Responsible Party):
PETHEMA Foundation
ClinicalTrials.gov Identifier:
NCT00504764
First received: July 19, 2007
Last updated: November 19, 2013
Last verified: November 2013
  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.

After remission induction, there are several options for postremission therapy Previous studies shows that risk of relapse is higher in patients treated with ATO postremission in monotherapy , than in other that receive ATO plus chemotherapy or transplantation (TPH). Also, compared with chemotherapy, ATO induction and consolidation has a favorable impact in posterior response to transplantation. It is due to a low toxicity or a best quality of remission to TPH. It seems better, for these reasons, the intensification with TPH (autologous or allogenic) in patients with relapsed APL treated with ATO. For another hand, patients no candidates to TPH can be treated with ATO combined with other active agents in APL, as ATRA, anthracyclines o Mylotarg


Condition Intervention Phase
Acute Promyelocytic Leukemia
Drug: Arsenic Trioxide
Procedure: Autologous Transplantation
Procedure: Allogenic Transplantation
Drug: ATRA
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: APL-R2007: Treatment of Relapsed Promyelocytic Leukemia With Arsenic Trioxide (ATO)

Resource links provided by NLM:


Further study details as provided by PETHEMA Foundation:

Primary Outcome Measures:
  • Evaluate the hematological and molecular remission rate after induction and consolidation with ATO [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Evaluate the induction mortality with ATO in monotherapy [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Evaluate the hematological and molecular relapse rate in patients treated with autologous transplantation, allogenic transplantation or ATO + ATRA +/- Mylotarg [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluate kinetics of the MDR of PML/RARa during and after ATO [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Evaluate the mortality related with postremission treatment [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Side effects of ATO and the different treatments post-consolidation [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: July 2007
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Arsenic Trioxide

    Induction ATO 0.15 mg/kg/day IV until CR or a maximum of 60 days In isolated molecular relapse ATO will be administered at same dose, 5 days a week, during 6 weeks.

    Consolidation ATO 0.15 mg/kg/day IV 5 days week, during 5 weeks

    Procedure: Autologous Transplantation
    Autologous Transplantation
    Procedure: Allogenic Transplantation
    Allogenic Transplantation
    Drug: ATRA
    Consolidation: ATRA 45 mg/m²/day oral during 5 weeks
  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • ECOG ≤ 3.
  • Patients in first or subsequent hematological or molecular relapse of APL
  • Persistence of a positive PCR (positive PCR after 3 consolidation cycles of first line therapy).
  • Diagnostic measures Confirmation of relapse by RT-PCR of PML/RARa, cytogenetics, FISH or positive PGM3.
  • Age over 18 years (No upper age limit)
  • Informed consent of the patient

Exclusion Criteria:

  • ECOG 4.
  • Heart failure NYHA grade III and IV.
  • Renal or hepatic failure WHO grade ³III
  • Positive HIV.
  • Psychological dysfunction
  • Associated active neoplasia
  • Pregnancy.
  • Arsenic Hypersensibility.
  • QTc-interval prolonged over 460 msec before therapy (normal electrolytes, no other drugs prolonging the QT-interval )
  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: NCT00504764

Contacts
Contact: Sanz Miguel Angel, Dr 34 (96) 197 3057 msanz@uv.es
Contact: Priego Miguel, Data manager 34 635 964 539 miguepriego@gmail.com

  Show 86 Study Locations
Sponsors and Collaborators
PETHEMA Foundation
Investigators
Study Chair: Sanz Miguel Angel, Dr Hospital La Fe
Study Chair: Esteve Jordi, Dr Hospital Clinic of Barcelona
Study Chair: Montesinos Pau, Dr Hospital general de Valencia
  More Information

Additional Information:
No publications provided

Responsible Party: PETHEMA Foundation
ClinicalTrials.gov Identifier: NCT00504764     History of Changes
Other Study ID Numbers: LAP-R2007
Study First Received: July 19, 2007
Last Updated: November 19, 2013
Health Authority: Spain: Ministry of Health

Keywords provided by PETHEMA Foundation:
Relapsed Acute Promyelocytic Leukemia
Arsenic Trioxide

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

ClinicalTrials.gov processed this record on October 21, 2014