Treatment of Relapsed Promyelocytic Leukemia With Arsenic Trioxide (ATO)
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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) |
- 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 ]
- 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 2014 |
| Estimated Primary Completion Date: | December 2013 (Final data collection date for primary outcome measure) |
-
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
Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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| 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| Study Chair: | Sanz Miguel Angel, Dr | Hospital La Fe |
| Study Chair: | Esteve Jordi, Dr | HOSPITAL CLÍNIC 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: | February 27, 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 Neoplasms by Histologic Type Neoplasms Leukemia, Myeloid, Acute |
Leukemia, Myeloid Arsenic trioxide Antineoplastic Agents Therapeutic Uses Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 19, 2013