Clinical trial NCT00777036: A Phase II Study of Dasatinib in Children and Adolescents With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia (CML) or With Ph+ Leukemias Resistant or Intolerant to Imatinib
Official title: A Phase II Study of Dasatinib Therapy in Children and Adolescents With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia or With Ph+ Leukemias Resistant or Intolerant to Imatinib
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Keywords: Leukemia, Pediatric
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2008-10-22
Enrollment: 130
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether dasatinib is safe and effective in children and adolescents with newly diagnosed chronic myeloid leukemia (CML), or in children with Ph+ acute lymphoblastic leukemia (ALL), accelerated or blast phases CML who relapse after imatinib or who are resistant or intolerant to imatinib. The side effects of this oral investigational drug in children and adolescents will be evaluated


Eligibility criteria: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

* CP-CML who prove resistant or intolerant to imatinib (Cohort 1)
* Ph+ ALL, AP-CML, or BP-CML who are resistant or intolerant to or who relapse after imatinib therapy (Cohort 2)
* Newly diagnosed, treatment naive CP-CML (Cohort 3)
* Lansky or Karnofsky scale \>50
* Life expectancy ≥12 weeks
* Adequate hepatic and renal function
* Written informed consent
* Target Population for the PK substudy must obtain written informed consent from subject, or from parents or legal guardians for minor subjects, according to local law and regulation
* Target Population for the PK substudy subjects must have CP-CML and be taking daily dasatinib (tablets or PFOS) either as part of Cohort 1 or Cohort 3 of this protocol. Patients receiving commercial dasatinib tablets outside of this protocol may be invited to participate in this PK substudy
* Target Population for the PK substudy subjects with CP-CML who are tolerating dasatinib tablet dose of at least 60 mg/m2 or dasatinib PFOS dose of at least 72 mg/m2
* Target Population for the PK substudy prior exposure to imatinib or other TKI therapy is permissible
* Target Population for the PK substudy subjects must meet relevant inclusion criteria

Exclusion Criteria:

* Eligibility for potentially-curative therapy including hematopoietic stem-cell transplantation
* Symptomatic CNS involvement (other than signs and symptoms caused by leptomeningeal disease)
* Isolated extramedullary disease
* Prior therapy with Dasatinib
* Target Population for the PK substudy subjects participating in the PK substudy must comply with the relevant exclusion criteria
* Target Population for the PK substudy subjects are not allowed to use proton pump inhibitors, H2 antagonists, CYP3A4 inhibitors and inducers when entering the PK substudy

Other inclusion/exclusion criteria may apply

Primary outcomes:
measure: Major Cytogenetic Response (MCyR) Rate
timeFrame: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
measure: Complete Hematologic Response (CHR) Rate
timeFrame: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
measure: Complete Cytogenetic Response (CCyR) Rate
timeFrame: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
Secondary outcomes:
measure: Major Cytogenetic Response (MCyR) Rate in Cohort 2
timeFrame: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
measure: Complete Hematologic Response (CHR) Rate in Cohorts 1 and 3
timeFrame: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
measure: Rate of Best Cytogenetic Response
timeFrame: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
measure: Time to Major Cytogenetic Response (MCyR)
timeFrame: From first dose until MCyR criteria are met (assessed up to September 2016, approximately 90 months)
measure: Duration of Major Cytogenetic Response (MCyR)
timeFrame: From first day criteria are met for MCyR until the date PD is reported or death (assessed up to September 2016, approximately 90 months)
measure: Time to Complete Cytogenetic Response (CCyR)
timeFrame: From first dose until CCyR criteria are met, assessed up to September 2016 (approximately 90 months)
measure: Duration of Complete Cytogenetic Response (CCyR)
timeFrame: From first day criteria are met for CCyR until the date of progressive disease or death (assessed up to September 2016, approximately 90 months)
measure: Progression-Free Survival (PFS) Rate at 2 Years
timeFrame: 2 years
measure: Time to Complete Hematologic Response (CHR)
timeFrame: From first dose until CHR criteria are met, assessed up to September 2016 (approximately 90 months)
measure: Duration of Complete Hemotologic Response (CHR)
timeFrame: From first day criteria are met for CHR until date of disease progression or death (assessed up to September 2016, approximately 90 months)
measure: Disease-Free Survival Rate at 2 Years
timeFrame: 2 years
measure: Overall Survival (OS) Rate at 2 Years
timeFrame: 2 years
measure: Major Molecular Response (MMR) Rate
timeFrame: From date of first treatment to date of MMR (assessed up to September 2016, approximately 90 months)
measure: Complete Molecular Response (CMR) Rate
timeFrame: From date of first treatment to date of CMR (assessed up to September 2016, approximately 90 months)
measure: Major Cytogenetic Response (MCyR) Rate up to 2 Years
timeFrame: 24 months
measure: Complete Cytogenetic Response (CCyR) Rate up to 2 Years
timeFrame: 24 months
measure: Major Molecular Response (MMR) Rate up to 2 Years
timeFrame: 24 months
measure: Complete Molecular Response (CMR) Rate up to 2 Years
timeFrame: 24 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Local Institution
state: Alabama
city: Phoenix
country: United States
facility: Local Institution - 0005
state: Arizona
city: Phoenix
country: United States
facility: Phoenix Children'S Hospital
state: Arizona
city: Long Beach
country: United States
facility: Jonathan Jaques Children'S Cancer Center
state: California
city: Long Beach
country: United States
facility: Jonathan Jaques Children'S Cancer Center
state: California
city: Long Beach
country: United States
facility: Local Institution - 0001
state: California
city: Orange
country: United States
facility: Children'S Hospital Of Orange County
state: California
city: Orange
country: United States
facility: Local Institution - 0024
state: California
city: Aurora
country: United States
facility: Children'S Hospital
state: Colorado
city: Aurora
country: United States
facility: Local Institution - 0004
state: Colorado
city: Atlanta
country: United States
facility: Children's Healthcare Of Atlanta - Egleston
state: Georgia
city: Atlanta
country: United States
facility: Local Institution - 047
state: Georgia
city: Chicago
country: United States
facility: Children's Hospital of Chicago
state: Illinois
city: Chicago
country: United States
facility: Local Institution - 0072
state: Illinois
city: Chicago
country: United States
facility: Local Institution
state: Illinois
city: Boston
country: United States
facility: Dana Faber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute.
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0040
state: Massachusetts
city: New York
country: United States
facility: Stephen D. Hassenfeld Children'S Center
state: New York
city: New York
country: United States
facility: Local Institution - 0061
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
city: Portland
country: United States
facility: Oregon Health & Sci Univ
state: Oregon
city: Portland
country: United States
facility: Local Institution - 0002
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Sci Univ
state: Oregon
city: Philadelphia
country: United States
facility: Children'S Hospital Of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Local Institution - 0014
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children'S Hospital Of Pittsburgh
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Local Institution - 0003
state: Pennsylvania
city: Houston
country: United States
facility: Local Institution - 0035
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: Local Institution - 0048
state: Texas
city: Houston
country: United States
facility: Texas Children'S Cancer Center
state: Texas
city: Seattle
country: United States
facility: Local Institution - 0028
state: Washington
city: Seattle
country: United States
facility: Seattle Children'S
state: Washington
city: Bunos Aires
country: Argentina
facility: Local Institution - 0043
state: Buenos Aires
city: Bunos Aires
country: Argentina
facility: Local Institution
state: Buenos Aires
city: El Palomar
country: Argentina
facility: Hospital Nacional Profesor Alejandro Posadas
state: Buenos Aires
city: El Palomar
country: Argentina
facility: Local Institution - 0049
state: Buenos Aires
city: Cordoba
country: Argentina
facility: Local Institution - 0042
city: Cordoba
country: Argentina
facility: Local Institution
city: Randwick
country: Australia
facility: Local Institution - 065
state: New South Wales
city: Randwick
country: Australia
facility: Local Institution
state: New South Wales
city: Westmead
country: Australia
facility: Local Institution - 069
state: New South Wales
city: Westmead
country: Australia
facility: Local Institution
state: New South Wales
city: Sth Brisbane
country: Australia
facility: Local Institution - 0064
state: Queensland
city: Sth Brisbane
country: Australia
facility: Local Institution
state: Queensland
city: North Adelaide
country: Australia
facility: Local Institution - 067
state: South Australia
city: North Adelaide
country: Australia
facility: Local Institution
state: South Australia
city: Parkville
country: Australia
facility: Local Institution - 0066
state: Victoria
city: Parkville
country: Australia
facility: Local Institution
state: Victoria
city: Curitiba
country: Brazil
facility: Local Institution - 0021
state: Parana
city: Curitiba
country: Brazil
facility: Local Institution
state: Parana
city: Porto Alegre
country: Brazil
facility: Local Institution - 0022
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: São Paulo
country: Brazil
facility: Local Institution - 0019
state: SAO Paulo
city: Campinas
country: Brazil
facility: Local Institution - 0020
city: Campinas
country: Brazil
facility: Local Institution
city: Sao Paulo
country: Brazil
facility: Local Institution - 0039
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Calgary
country: Canada
facility: Alberta Children'S Hospital
state: Alberta
city: Calgary
country: Canada
facility: Local Institution - 0079
state: Alberta
city: Edmonton
country: Canada
facility: Local Institution - 0078
state: Alberta
city: Edmonton
country: Canada
facility: Stollery Children'S Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Bc Children'S Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: Local Institution - 077
state: British Columbia
city: Halifax
country: Canada
facility: Iwk Health Centre
state: Nova Scotia
city: Halifax
country: Canada
facility: Local Institution - 073
state: Nova Scotia
city: Ottawa
country: Canada
facility: Children'S Hospital Of Eastern Ontario
state: Ontario
city: Ottawa
country: Canada
facility: Local Institution - 086
state: Ontario
city: Toronto
country: Canada
facility: Local Institution - 076
state: Ontario
city: Toronto
country: Canada
facility: The Hospital For Sick Children
state: Ontario
city: Montreal
country: Canada
facility: Chu Ste-Justine
state: Quebec
city: Montreal
country: Canada
facility: Local Institution - 080
state: Quebec
city: Lyon
country: France
facility: Local Institution - 0030
city: Lyon
country: France
facility: Local Institution
city: Nantes
country: France
facility: Local Institution - 0032
city: Nantes
country: France
facility: Local Institution
city: Paris Cedex 12
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution - 0037
city: Paris
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution - 0029
city: Paris
country: France
facility: Local Institution
city: Poitiers
country: France
facility: Local Institution - 036
city: Poitiers
country: France
facility: Local Institution
city: Frankfurt
country: Germany
facility: Local Institution - 075
city: Frankfurt
country: Germany
facility: Local Institution
city: Hannover
country: Germany
facility: Local Institution - 0074
city: Hannover
country: Germany
facility: Local Institution
city: Navrangpura, Ahmedabad
country: India
facility: Local Institution - 0089
state: Gujarat
city: Navrangpura, Ahmedabad
country: India
facility: Local Institution
state: Gujarat
city: Bangalore
country: India
facility: Local Institution
state: Karnataka
city: Mumbai
country: India
facility: Local Institution
state: Maharashtra
city: Pune
country: India
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state: Maharashtra
city: Pune
country: India
facility: Local Institution
state: Maharashtra
city: Madurai
country: India
facility: Local Institution - 0093
state: Tamil Nadu
city: Madurai
country: India
facility: Local Institution
state: Tamil Nadu
city: Vellore
country: India
facility: Local Institution
state: Tamilnadu
city: Bangalore
country: India
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city: Kolkatta
country: India
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city: Kolkatta
country: India
facility: Local Institution
city: Mumbai
country: India
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city: Mumbai
country: India
facility: Local Institution
city: Trivandrum
country: India
facility: Local Institution - 0084
city: Trivandrum
country: India
facility: Local Institution
city: Bologna
country: Italy
facility: Local Institution - 038
city: Bologna
country: Italy
facility: Local Institution
city: Monza (MB)
country: Italy
facility: Local Institution
city: Monza
country: Italy
facility: Local Institution - 006
city: Roma
country: Italy
facility: Local Institution - 070
city: Roma
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution - 0059
city: Roma
country: Italy
facility: Local Institution
city: Torino
country: Italy
facility: Local Institution - 015
city: Torino
country: Italy
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0092
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0091
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Cuauhtémoc
country: Mexico
facility: Local Institution - 0051
state: Distrito Federal
city: Df
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Mexico D.f.
country: Mexico
facility: Local Institution - 0052
state: Distrito Federal
city: Mexico D.f.
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Mexico, D. F.
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Mexico
country: Mexico
facility: Local Institution - 0053
state: Distrito Federal
city: Mexico
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Hospital Civil De Guadalajara - Nuevo Dr. Juan I. Menchaca
state: Jalisco
city: Guadalajara
country: Mexico
facility: Local Institution - 0054
state: Jalisco
city: Monterrey, N.l.
country: Mexico
facility: Local Institution - 0060
state: Nuevo Leon
city: Monterrey, N.l.
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Monterrey
country: Mexico
facility: Local Institution - 0050
state: Nuevo Leon
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Rotterdam
country: Netherlands
facility: Local Institution - 0007
city: Rotterdam
country: Netherlands
facility: Local Institution
city: Utrecht
country: Netherlands
facility: Local Institution - 0099
city: Bucharest
country: Romania
facility: Local Institution - 0095
city: Bucharest
country: Romania
facility: Local Institution
city: Sector 2
country: Romania
facility: Local Institution - 0097
city: Moscow
country: Russian Federation
facility: Local Institution - 0017
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution - 0023
city: Moscow
country: Russian Federation
facility: Local Institution
city: Saint-petersburg
country: Russian Federation
facility: Local Institution - 0018
city: Saint-petersburg
country: Russian Federation
facility: Local Institution
city: Singapore
country: Singapore
facility: Local Institution - 0071
city: Singapore
country: Singapore
facility: Local Institution
city: Bloemfontein
country: South Africa
facility: Local Institution - 0055
state: FREE State
city: Bloemfontein
country: South Africa
facility: Local Institution
state: FREE State
city: Pretoria
country: South Africa
facility: Local Institution - 058
state: Gauteng
city: Pretoria
country: South Africa
facility: Local Institution
state: Gauteng
city: Cape Town
country: South Africa
facility: Local Institution - 0057
state: Western CAPE
city: Cape Town
country: South Africa
facility: Local Institution
state: Western CAPE
city: Tygerberg
country: South Africa
facility: Local Institution - 062
state: Western CAPE
city: Tygerberg
country: South Africa
facility: Local Institution
state: Western CAPE
city: Barcelona
country: Spain
facility: Local Institution - 0013
city: Barcelona
country: Spain
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution - 0012
city: Barcelona
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution - 0011
city: Madrid
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution - 0010
city: Madrid
country: Spain
facility: Local Institution
city: Malaga
country: Spain
facility: Local Institution - 0041
city: Malaga
country: Spain
facility: Local Institution
city: Valencia
country: Spain
facility: Local Institution - 0033
city: Valencia
country: Spain
facility: Local Institution
city: Valencia
country: Spain
facility: Local Institution
city: Glasgow
country: United Kingdom
facility: Local Institution - 0016
state: Central
city: Glasgow
country: United Kingdom
facility: Local Institution
state: Central
city: Sutton
country: United Kingdom
facility: Local Institution - 0009
state: Surrey
city: Sutton
country: United Kingdom
facility: Local Institution
state: Surrey
city: Birmingham
country: United Kingdom
facility: Local Institution - 0008
state: West Midlands
city: Birmingham
country: United Kingdom
facility: Local Institution
state: West Midlands
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Gore L, Kearns PR, de Martino ML, Lee, De Souza CA, Bertrand Y, Hijiya N, Stork LC, Chung NG, Cardos RC, Saikia T, Fagioli F, Seo JJ, Landman-Parker J, Lancaster D, Place AE, Rabin KR, Sacchi M, Swanink R, Zwaan CM. Dasatinib in Pediatric Patients With Chronic Myeloid Leukemia in Chronic Phase: Results From a Phase II Trial. J Clin Oncol. 2018 May 1;36(13):1330-1338. doi: 10.1200/JCO.2017.75.9597. Epub 2018 Mar 2.