Study Description
The study is designed to compare the tolerability of asciminib versus nilotinib for the treatment of newly diagnosed, previously untreated patients with Positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP).
This study is a phase IIIb, multi-center, open-label, randomized study of oral asciminib 80 mg once daily (QD) versus nilotinib 300 mg twice daily (BID) in adult patients with newly diagnosed Ph+ CML-CP.
Participants will be randomized in the study in a 1:1 ratio to asciminib or nilotinib. No crossover of study treatment across arms will be allowed.
Participants will be treated until unacceptable toxicity, disease progression and/or at the discretion of the investigator or the participants. A safety follow up visit/call will be performed approximately 30 days after end of treatment visit. Participants who discontinue study treatment prematurely due to any reason, will be followed up for survival and progression (to Accelerated Phase (AP)/Blast Crisis (BC)) up until end of study.
Interventions
Asciminib
Nilotinib
Eligibility Criteria
Inclusion Criteria:
Patients with CML-CP within 3 months of diagnosis.
Diagnosis of CML-CP (ELN 2020 criteria) with cytogenetic confirmation of the Philadelphia chromosome
Documented chronic phase CML will meet all the below criteria Baccarani et al 2013:
< 15% blasts in peripheral blood and bone marrow,
< 30% blasts plus promyelocytes in peripheral blood and bone marrow,
< 20% basophils in the peripheral blood,
PLT count ≥ 100 x 10^9/L (≥ 100,000/mm3), except treatment induced thrombocytopenia
No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly.
Evidence of typical BCR::ABL1 transcript [e14a2 and/or e13a2] which is amenable to standardized RQ-PCR quantification by the central laboratory assessment.
ECOG performance status of 0 or 1.
Adequate end organ function as defined by:
Total bilirubin (TBL) < 3 x ULN; patients with Gilbert's syndrome may only be included if TBL ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN,
CrCl ≥ 30 mL/min as calculated using Cockcroft-Gault formula, Serum lipase ≤ 1.5 x ULN. For serum lipase > ULN - ≤ 1.5 x ULN, value must be considered not clinically significant and not associated with risk factors for acute pancreatitis.
Patients must have the following laboratory values within normal limits or corrected to within normal limits with supplements prior to randomization:
Potassium (potassium increase of up to 6.0 mmol/L is acceptable if associated with CrCl* ≥ 90 mL/min)**,
Total calcium (corrected for serum albumin); (calcium increase of up to 12.5 mg/dl or 3.1 mmol/L is acceptable if associated with CrCl* ≥ 90 mL/min),
Magnesium (magnesium increase of up to 3.0 mg/dL or 1.23 mmol/L if associated with CrCl* ≥ 90 mL/min),
For patients with mild to moderate renal impairment (CrCl* ≥ 30 mL/min and <90 mL/min) - potassium, total calcium (corrected for serum albumin) and magnesium should be within normal limits or corrected to within normal limits with supplements prior to randomization.
CrCl as calculated using Cockcroft-Gault formula. **Pseudohyperkaliemia in case of thrombocytosis is not an exclusion criterion.
Exclusion Criteria:
Previous treatment of CML with any other anticancer agents including chemotherapy and/or biologic agents or prior stem cell transplant, with the exception of hydroxyurea and/or anagrelide.
Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required).
Impaired cardiac function or cardiac repolarization abnormality including but not limited to any one of the following:
History of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG) within 6 months prior to starting study treatment.
Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block).
QTcF ≥ 450 ms on the average of three serial baseline ECG (using the QTcF formula). If QTcF ≥ 450 ms and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTcF.
Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia.
Concomitant medication(s) with a "Known risk of Torsades de Pointes" per www.crediblemeds.org that cannot be discontinued or replaced 7 days prior to starting study drug by safe alternative medication.
Inability to determine the QTcF interval.
Severe and/or uncontrolled concurrent medical disease that in the opinion of the Investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. uncontrolled diabetes, active or uncontrolled infection; uncontrolled arterial or pulmonary hypertension, uncontrolled clinically significant hyperlipidemia).
History of significant congenital or acquired bleeding disorder unrelated to cancer.
Major surgery within 4 weeks prior to study entry or patients who have not recovered from prior surgery.
History of other active malignancy within 3 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively.
History of acute pancreatitis within 1 year prior to randomization or medical history of chronic pancreatitis.
History of chronic liver disease leading to severe hepatic impairment, or ongoing acute liver disease.
Known history of chronic Hepatitis B (HBV), or chronic Hepatitis C (HCV) infection. Testing for Hepatitis B surface antigen (HBs Ag) and Hepatitis B core antibody (HBc Ab/anti HBc) will be performed at screening. If anti-HBc is positive, HBV-DNA evaluation will be carried out at screening. A patient having positive HBV-DNA will not be enrolled in the study. Also, a patient with positive HBsAg will not be enrolled in the study. HCV Ab testing will also be performed at screening. For details on the criteria see Appendix 4.
History of Human Immunodeficiency Virus (HIV) unless well-controlled on a stable dose of anti-retroviral therapy at the time of screening.
Other protocol-defined Inclusion/exclusion criteria will apply.
Study Location
Novartis Investigative Site
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Caba,Buenos Aires,C1181ACH,Argentina
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Caba,Buenos Aires,C1221ADH,Argentina
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Buenos aires,C1039AAC,Argentina
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Buenos Aires,C1114AAN,Argentina
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Buenos Aires,C1425AUM,Argentina
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Pleven,5800,Bulgaria
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Sofia,1413,Bulgaria
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Plovdiv,4002,Bulgaria
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Sofia,1431,Bulgaria
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Sofia,1797,Bulgaria
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Varna,9010,Bulgaria
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Toronto,Ontario,M5G 2M9,Canada
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Plzen-Bory,30599,Czech Republic
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Praha 10,100 34,Czech Republic
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Brno Bohunice,Czech Republic,625 00,Czech Republic
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Praha 2,Czech Republic,128 20,Czech Republic
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Clermont Ferrand,63003,France
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Lyon,69373,France
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Paris 10,75475,France
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Bordeaux,33076,France
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Lille,59037,France
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Poitiers,86000,France
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Vandoeuvre les Nancy cedex,54511,France
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Caen Cedex,14033,France
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Nantes Cedex 1,44093,France
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Toulouse,31059,France
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Marseille,13273,France
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Strasbourg,67200,France
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Nice,06202,France
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Erlangen,91054,Germany
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Velbert,North Rhine-Westphalia,42551,Germany
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Aachen,52074,Germany
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Tuebingen,72076,Germany
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Paderborn,33098,Germany
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Bonn,53105,Germany
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Regensburg,93049,Germany
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Essen,45147,Germany
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Muenchen,Bayern,81241,Germany
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Wuerzburg,97080,Germany
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Magdeburg,39104,Germany
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Halle S,06120,Germany
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Leipzig,04103,Germany
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Augsburg,86179,Germany
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Frankfurt,60590,Germany
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Muenchen,80377,Germany
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Mannheim,Baden Wuerttemberg,68305,Germany
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Ulm,89081,Germany
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Hamburg,20246,Germany
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Bad Saarow,15526,Germany
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Freiburg,79106,Germany
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Jena,07740,Germany
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Marburg,35039,Germany
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Bremen,28177,Germany
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Hannover,30161,Germany
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Dresden,Sachsen,01307,Germany
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Chemnitz,09113,Germany
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Bayreuth,95445,Germany
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Heidelberg,69120,Germany
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Luebeck,23538,Germany
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Berlin,13353,Germany
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Thessaloniki,GR,570 10,Greece
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Athens,106 76,Greece
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Ioannina,GR,455 00,Greece
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Larissa,GR,411 10,Greece
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Athens,115 27,Greece
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Patras,265 00,Greece
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Budapest,1085,Hungary
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Budapest,1097,Hungary
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Eger,3300,Hungary
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Rishikesh,Uttarakhand,249203,India
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Ahmedabad,Gujrat,380009,India
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Varanasi,Uttar Pradesh,221010,India
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New Delhi,110029,India
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Chennai,Tamilnadu,600036,India
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Milano,MI,20162,Italy
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Torino,TO,10126,Italy
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Bari,BA,70124,Italy
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Meldola,FC,47014,Italy
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Pisa,PI,56126,Italy
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Amman,11941,Jordan
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Bundang Gu,Gyeonggi Do,13620,Korea, Republic of
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Uijeongbu si,Gyeonggi Do,11759,Korea, Republic of
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Alor Setar,Kedah,05460,Malaysia
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Penang,10050,Malaysia
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Petaling Jaya,Selangor Darul Ehsan,46150,Malaysia
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Kuala Lumpur,59100,Malaysia
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Kuching,Sarawak,93586,Malaysia
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Dordrecht,3318AT,Netherlands
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Muscat,123,Oman
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Bucharest,030 171,Romania
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Timisoara,300079,Romania
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Bucuresti,021494,Romania
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Cluj-Napoca,400124,Romania
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Craiova,200136,Romania
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Sibiu,550245,Romania
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Tg Mures,Mures,540136,Romania
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Bucharest,District 2,022328,Romania
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Singapore,119228,Singapore
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Singapore,169608,Singapore
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Singapore,S308433,Singapore
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Bratislava,85107,Slovakia
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Kosice,Slovak Republic,040 66,Slovakia
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Soweto,Gauteng,2013,South Africa
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Pretoria,0044,South Africa
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Genève,1211,Switzerland
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Istanbul,TUR,34098,Turkey
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Izmir,35040,Turkey
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Ankara,06100,Turkey
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Abu Dhabi,United Arab Emirates
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Gwent,NP9 2UB,United Kingdom
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London,SE5 9RS,United Kingdom
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London,W12 0HS,United Kingdom
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Glasgow,G12 0YN,United Kingdom
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Gloucester,GL1 3NN,United Kingdom
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Truro,Cornwall,TR1 3LJ,United Kingdom
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Dallas,Shawnty Witham (512-421-4100) email: [email protected] -- Jason M Melear,75251 - Texas,United States
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Baton Rouge,Paige Pigee email: [email protected] -- Michael Castine III,70809 - Louisiana,United States
Oncology Hematology Care Inc .
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Cincinnati,Zachary Beck email: [email protected] -- Kruti Patel,45242 - Ohio,United States
Virginia Oncology Associates VOA - Princess Anne
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Norfolk,Emily Jones (757-368-0437) email: [email protected] -- Celeste Bremer,23502 - Virginia,United States
Illinois Cancer Care
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Peoria,Heather Thulean (309-243-3661) email: [email protected] -- Srinivas Jujjavarapu,61615 - Illinois,United States
Regions Hospital Oncology Research Consortium
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Saint Paul,Yan Ji,55101 - Minnesota,United States
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Eugene,Alexandra Chavez email: [email protected] -- Luke Fletcher,97401 - Oregon,United States
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Kingwood,Whitney Nwole (281-809-0676) email: [email protected] -- Saleha Sajid,77339 - Texas,United States
Rocky Mountain Cancer Centers USOR
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Boulder,Lee Dimopoulos (303-385-2000) email: [email protected] -- David J Andorsky,80304 - Colorado,United States
Messino Cancer Centers
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Asheville,Taylor McNeely email: [email protected] -- Andrew Beardsley,28806 - North Carolina,United States
Sarah Cannon Research Institute HCA Healthcare Research Inst
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Nashville,Vanesa Veletanlic (615-515-1900) email: [email protected] -- Stephen Strickland,37203 - Tennessee,United States
Arizona Oncology Associates .
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Phoenix,Alan Langerak,85016 - Arizona,United States
Minnesota Oncology Hematology P A Minnesota Oncology Hematology
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Minneapolis,Brianna Lennox (612-884-6300) email: [email protected] -- Danielle Tippit,55404 - Minnesota,United States
Florida Cancer Specialists Dept of Oncology (2)
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Fort Myers,Kelly Whitehead (+1 727 216 1143) email: [email protected] -- Adewale Alade Fawole,33901 - Florida,United States
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