Effectiveness and Safety of Therapy Based on Attenuated ATO Plus Low-Dose ATRA in Patients With APL.
Study Details
Study Description
Brief Summary
ATRA is the standard of care for all patients with APL. The use of lower doses of ATRA has been shown since the 1990s to achieve therapeutic efficacy with doses of 25mg/m2/day. ATO demonstrated considerable effectiveness in this disease. More recently, an attenuated regimen has been proven to be effective. In this study we intent to demonstrate the effectiveness of combined therapy of low-dose ATRA plus attenuated dose ATO.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Detailed Description
The use of lower doses of ATRA has been shown since the 1990s to achieve therapeutic plasma concentrations sufficient to achieve therapeutic efficacy with doses of 25mg/m2/day. ATO alone demonstrated considerable effectiveness in this disease. More recently, an attenuated regimen has been proven to be effective in inducing similar remission rates and achieving prolonged survival, also demonstrating a reduction in associated toxicities, mainly hepatic and cardiac when using this new scheme.
We will conduct a phase 1/2, non-randomized, single center, non-comparative clinical trial to demonstrate the effectiveness of combined therapy of low-dose ATRA plus attenuated dose ATO which is accessible to a population with limited resources while maintaining acceptable efficacy and safety.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Induction with attenuated ATO plus low-dose ATRA Remission induction therapy will be administrated as ATRA 25/mg/m2/day for 28 continuous days without interruption if APL is suspected. ATO 0.3mg/kg/day for days 1-5 (5 doses) and then 0.25 mg/kg/day every other day twice a week for the next 3 weeks (6 doses). |
Drug: Arsenic trioxide
Patients will receive ATO 0.3mg/kg/day for days 1-5 (5 doses) and then 0.25 mg/kg/day every other day twice a week for the next 3 weeks (6 doses).
Other Names:
Drug: all-trans retinoic acid
Patients will receive ATRA 25/mg/m2/day for 28 continuous days without interruption.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Safety of therapy [28 days]
Safety will be defined by the number of patients deceased after 1 induction cycle of 28 days
Secondary Outcome Measures
- Overall response [28 days]
Overall response rate was definide as partial response plus complete response after 1
- Progression-free survival [6 months]
Time from achievement of complete hematologic remission to relapse
- Event-free survival [6 months]
Time from registration to induction failure, relapse, or death.
- Rate of treatment discontinuation due to toxicity. [28 days]
Rate of treatment discontinuation due to toxicity.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age >18 years
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Both genders
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new diagnosis of APL
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Diagnosis of relapsed APL who have not been previously treated with ATO
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Morphological diagnosis of APL confirmed by PCR or FISH
Exclusion Criteria:
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Poor functional status (ECOG>2)
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Organic dysfunction (Marshall score ≥2)
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Pregnancy
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Heart failure (NYHA III or IV)
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Renal failure (GFR <30 ml/min/1.72m2)
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History of ventricular arrhythmias or uncontrolled arrhythmias
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Acute myocardial infarction, unstable angina, or stable angina in the last six months
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Uncontrolled active infection
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Liver disease (Child-Pugh C)
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Hopsital Universitario Dr. Jose E. Gonzalez, Centro Universitario contra el Cancer | Monterrey | Nuevo Leon | Mexico | 64460 |
Sponsors and Collaborators
- Hospital Universitario Dr. Jose E. Gonzalez
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Burnett AK, Russell NH, Hills RK, Bowen D, Kell J, Knapper S, Morgan YG, Lok J, Grech A, Jones G, Khwaja A, Friis L, McMullin MF, Hunter A, Clark RE, Grimwade D; UK National Cancer Research Institute Acute Myeloid Leukaemia Working Group. Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2015 Oct;16(13):1295-305. doi: 10.1016/S1470-2045(15)00193-X. Epub 2015 Sep 14.
- Castaigne S, Lefebvre P, Chomienne C, Suc E, Rigal-Huguet F, Gardin C, Delmer A, Archimbaud E, Tilly H, Janvier M, et al. Effectiveness and pharmacokinetics of low-dose all-trans retinoic acid (25 mg/m2) in acute promyelocytic leukemia. Blood. 1993 Dec 15;82(12):3560-3.
- Chen GQ, Shen ZX, Wu F, Han JY, Miao JM, Zhong HJ, Li XS, Zhao JQ, Zhu J, Fang ZW, Chen SJ, Chen Z, Wang ZY. Pharmacokinetics and efficacy of low-dose all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Leukemia. 1996 May;10(5):825-8.
- Chen GQ, Zhu J, Shi XG, Ni JH, Zhong HJ, Si GY, Jin XL, Tang W, Li XS, Xong SM, Shen ZX, Sun GL, Ma J, Zhang P, Zhang TD, Gazin C, Naoe T, Chen SJ, Wang ZY, Chen Z. In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Blood. 1996 Aug 1;88(3):1052-61.
- Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ, Wang ZY. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988 Aug;72(2):567-72.
- Jaime-Pérez JC, González-Leal XJ, Pinzón-Uresti MA, Gómez-De León A, Cantú-Rodríguez OG, Gutiérrez-Aguirre H, Gómez-Almaguer D. Is There Still a Role for Low-Dose All-Transretinoic Acid in the Treatment of Acute Promyelocytic Leukemia in the Arsenic Trioxide Era? Clin Lymphoma Myeloma Leuk. 2015 Dec;15(12):816-9. doi: 10.1016/j.clml.2015.09.002. Epub 2015 Sep 25.
- HE22-00019