Safety and Efficacy of Nilotinib in Newly Diagnosed Chronic Myeloid Leukemia Patients

Chronic Myeloid Leukemia Clinical Trial

— ENESTxtnd  

Official title:

Extending Molecular Responses With Nilotinib in Newly Diagnosed Chronic Myeloid Leukemia (CML) Patients in Chronic Phase

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01254188
• Other study ID #: CAMN107E2401
• Status: Completed
• Phase: Phase 3
• First received: December 2, 2010
• Last updated: February 3, 2016
• Start date: April 2011
• Est. completion date: November 2014

Study information

• Verified date: February 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAlgeria: Ministry of HealthArgentina: Ministry of HealthAustralia: Institutional Review BoardBahrain: Institutional Review BoardBrazil: Ministry of HealthCanada: Health CanadaEgypt: Ministry of Health and PopulationIndia: Drugs Controller General IndiaIsrael: Ministry of HealthLebanon: Institutional Review BoardMalaysia: Ministry of HealthMexico: Federal Commission for Sanitary Risks ProtectionMorocco: Ministry of Public HealthPhilippines: Philippine Food and Drug AdministrationQatar: Institutional Review BoardRussia: Ministry of HealthSaudi Arabia: Saudi Food & Drug AdministrationSouth Africa: Department of Health
• Study type: Interventional

Clinical Trial Summary

This study will further investigate the safety and efficacy of nilotinib in newly diagnosed chronic myeloid leukemia patients in the chronic phase

Other known NCT identifiers

• NCT01580059

Recruitment information / eligibility

• Status: Completed
• Enrollment: 421
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

-Patients with chronic myeloid leukemia in the chronic phase diagnosed within 6 months of study entry

Exclusion Criteria:

• Treatment with tyrosine kinase inhibitor or other antileukemic agents or treatments (including HSCT) for longer than 2 weeks, with exception of hydroxyurea and/or anagrelide

• Uncontrolled congestive heart failure or hypertension

• Myocardial infarction or unstable angina pectoris within past 12 months

• Known T315I mutations

• QTcF >450 msec

• Significant arrhythmias

Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

Intervention

Drug:
• Nilotinib
This was an open-label, single-arm, prospective, multi-center, Phase IIIb clinical study with nilotinib 300 mg bid treatment in newly diagnosed CML-CP patients not previously treated with imatinib therapy and diagnosed within 6 months of study entry. For patients insufficiently responding to nilotinib 300 mg bid, the dose may have been increased to 400 mg bid. Among patients with adverse events who had dose reduction, this study also allowed a possible re-escalation to 300 mg bid.

Locations

Country	Name	City	State
Algeria	Novartis Investigative Site	Alger	Bouzareah
Algeria	Novartis Investigative Site	Oran
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Paraná	Entre Rios
Australia	Novartis Investigative Site	Adelaide	South Australia
Australia	Novartis Investigative Site	Bedford Park	South Australia
Australia	Novartis Investigative Site	Box Hill	Victoria
Australia	Novartis Investigative Site	Canberra	Australian Capital Territory
Australia	Novartis Investigative Site	Clayton	Victoria
Australia	Novartis Investigative Site	Concord NSW	New South Wales
Australia	Novartis Investigative Site	Douglas	Queensland
Australia	Novartis Investigative Site	Fitzroy	Victoria
Australia	Novartis Investigative Site	Gosford	New South Wales
Australia	Novartis Investigative Site	Heidelberg	Victoria
Australia	Novartis Investigative Site	Hobart	Tasmania
Australia	Novartis Investigative Site	Kingswood	New South Wales
Australia	Novartis Investigative Site	Kogarah	New South Wales
Australia	Novartis Investigative Site	Liverpool	New South Wales
Australia	Novartis Investigative Site	Nedlands	Western Australia
Australia	Novartis Investigative Site	Parkville	Victoria
Australia	Novartis Investigative Site	Perth	Western Australia
Australia	Novartis Investigative Site	St. Leonards	New South Wales
Australia	Novartis Investigative Site	Westmead	New South Wales
Australia	Novartis Investigative Site	Wodonga	Victoria
Australia	Novartis Investigative Site	Woolloongabba	Queensland
Brazil	Novartis Investigative Site	Curitiba	PR
Brazil	Novartis Investigative Site	Goiania	GO
Brazil	Novartis Investigative Site	Porto Alegre	RS
Brazil	Novartis Investigative Site	Salvador	BA
Canada	Novartis Investigative Site	Barrie	Ontario
Canada	Novartis Investigative Site	Brampton	Ontario
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	Halifax	Nova Scotia
Canada	Novartis Investigative Site	Hamilton	Ontario
Canada	Novartis Investigative Site	London	Ontario
Canada	Novartis Investigative Site	Moncton	New Brunswick
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Québec	Quebec
Canada	Novartis Investigative Site	Saint John	New Brunswick
Canada	Novartis Investigative Site	Saskatoon	Saskatchewan
Canada	Novartis Investigative Site	St. John's	Newfoundland and Labrador
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Vancouver	British Columbia
Canada	Novartis Investigative Site	Vancouver	British Columbia
Canada	Novartis Investigative Site	Weston	Ontario
Canada	Novartis Investigative Site	Windsor	Ontario
Egypt	Novartis Investigative Site	Alexandria
Egypt	Novartis Investigative Site	Cairo
Egypt	Novartis Investigative Site	Cairo
Egypt	Novartis Investigative Site	Mansoura
India	Novartis Investigative Site	Pune	Maharashtra
India	Novartis Investigative Site	Tamil Nadu	Chennai
India	Novartis Investigative Site	Vellore	Tamil Nadu
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Petach Tikva
Israel	Novartis Investigative Site	Ramat Gan
Lebanon	Novartis Investigative Site	Beirut
Lebanon	Novartis Investigative Site	Saida
Malaysia	Novartis Investigative Site	Pulau Pinang
Malaysia	Novartis Investigative Site	Selangor
Mexico	Novartis Investigative Site	Hermosillo	Sonora
Mexico	Novartis Investigative Site	San Luis Potosi
Oman	Novartis Investigative Site	Muscat
Russian Federation	Novartis Investigative Site	Arkhangelsk	Russia
Russian Federation	Novartis Investigative Site	Ekaterinburg
Russian Federation	Novartis Investigative Site	Irkutsk
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Nizhnii Novgorod
Russian Federation	Novartis Investigative Site	Novosibirsk	Russia
Russian Federation	Novartis Investigative Site	Perm	Russia
Russian Federation	Novartis Investigative Site	Rostov-on-Don
Russian Federation	Novartis Investigative Site	Rostov-on-Don
Russian Federation	Novartis Investigative Site	Ryazan	Russia
Russian Federation	Novartis Investigative Site	St Petersburg	Russia
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	St-Petersburg
Russian Federation	Novartis Investigative Site	Tula
Russian Federation	Novartis Investigative Site	Tumen	Russia
Saudi Arabia	Novartis Investigative Site	Dammam
Saudi Arabia	Novartis Investigative Site	Jeddah
Saudi Arabia	Novartis Investigative Site	Jeddah
Saudi Arabia	Novartis Investigative Site	Riyadh
Saudi Arabia	Novartis Investigative Site	Riyadh
South Africa	Novartis Investigative Site	Bloemfontein
South Africa	Novartis Investigative Site	Observatory
South Africa	Novartis Investigative Site	Parktown
South Africa	Novartis Investigative Site	Pretoria
South Africa	Novartis Investigative Site	Soweto	Gauteng
Taiwan	Novartis Investigative Site	Lin-Kou
Taiwan	Novartis Investigative Site	Niaosong Township
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taipei	Taiwan, ROC
Thailand	Novartis Investigative Site	Chiang Mai
Thailand	Novartis Investigative Site	Muang
Tunisia	Novartis Investigative Site	Sousse	Tunisie
Tunisia	Novartis Investigative Site	Tunis
United Arab Emirates	Novartis Investigative Site	Dubai

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Algeria,  Argentina,  Australia,  Brazil,  Canada,  Egypt,  India,  Israel,  Lebanon,  Malaysia,  Mexico,  Oman,  Russian Federation,  Saudi Arabia,  South Africa,  Taiwan,  Thailand,  Tunisia,  United Arab Emirates, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Percentage of Patients Achieving MMR by 12 Months	MMR is defined as BCR-ABL ratio (%) on IS <= 0.1% (corresponds to >=3 log reduction of BCR-ABL transcripts from standardized baseline value). Clopper-Pearson method	12 months	No
Secondary	Time to Molecular Response at 24 Months	Estimated median time to first MMR by Kaplan-Meier method	24 months	No
Secondary	Duration of Major Molecular Response	Kaplan-Meier estimates of duration of first MMR among patients who achieved MMR (FAS) Duration of first MMR (months) = (Minimum date of (loss of first MMR , CML-related death, progression to AP/BC during study treatment, censoring) - date of first MMR + 1) / 30.4375	3, 6, 9, 12, 15, 18, 21, 24 Months after MMR was detected	No
Secondary	Complete Cytogenetic Response	Complete cytogenetic response (CCyR) is defined as a value of 0% Ph+ metaphases in bone marrow.	6 months	No
Secondary	Percentage of Participants Estimated to Maintain Their First CCyR for 6, 12, 18, and 24 Months After the First CCyR Was Achieved as Determined by Kaplan Meier Estimatation.	* CCyR = 0% Ph+ metaphases based on at least 20 metaphases from bone marrow cytogenetics.; Duration of first CCyR (months) = (date of CCyR loss or censoring - date of first CCyR +1) / 30.4375	6,12,18 and 24 months	No
Secondary	Overall Survival	OS was defined as the time between date of study entry and date of death due to any cause at any time during the study, including the follow-up period after discontinuation of treatment.	3, 6, 9, 12, 15, 18, 21, 24 Months	No
Secondary	Kaplan-Meier Estimates of Progression-free Survival	PFS was defined as the time from the date of study entry to the date of event defined as the first documented disease progression to AP/BC or the date of death from any cause occurring on treatment.	3,6,9,12,15,18,21,and 24 months	No
Secondary	Kaplan-Meier Estimates of Failure-free Survival	Time to event (months) = (date of event or censoring - date of study entry + 1) / 30.4375. Date of event is the earliest date of the following events during treatment : discontinuation of nilotinib for nilotinib-related adverse events, death due to any cause, progression to AP or BC, loss of PCyR, loss of CCyR, loss of CHR. Time is censored at the date of last assessment in the trial for patients without event.	3,6,9,12,15,18,21,and 24 months	No