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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00777036




Registration number
NCT00777036
Ethics application status
Date submitted
21/10/2008
Date registered
22/10/2008
Date last updated
29/01/2018

Titles & IDs
Public title
A Phase II Study of Dasatinib in Children and Adolescents With Newly Diagnosed Chronic Phase CML or With Ph+ Leukemias Resistant or Intolerant to Imatinib
Scientific title
A Phase II Study of Dasatinib in Children and Adolescents With Newly Diagnosed Chronic Phase CML or With Ph+ Leukemias Resistant or Intolerant to Imatinib
Secondary ID [1] 0 0
2008-002260-33
Secondary ID [2] 0 0
CA180-226
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dasatinib

Experimental: Cohort 1: Imatinib-resistant/intolerant CP-CML - Dasatinib 60 mg/m² tablet every day (QD) [with a maximum dose of 100 mg QD for subjects with high BSA] for minimum of 24 months, may continue as long as deriving clinical benefit
OR
Dasatinib 72 mg/m² powder for oral suspension (PFSO) QD [with a maximum dose of 120 mg QD for subjects with high BSA] for minimum of 24 months, may continue as long as deriving clinical benefit

Experimental: Cohort 2: Ph+ALL or AP- or BP-CML - Dasatinib 80 mg/m² tablet QD [with a maximum dose of 140 mg QD for subjects with high BSA] for minimum of 24 months, may continue as long as deriving clinical benefit
OR
Dasatinib 96 mg/m² PFSO QD [with a maximum dose of 170 mg QD for subjects with high BSA] for minimum of 24 months, may continue as long as deriving clinical benefit

Experimental: Cohort 3: Newly diagnosed, treatment naïve CP-CML - Dasatinib 60 mg/m² tablet QD [with a maximum dose of 100 mg QD for subjects with high BSA] for minimum of 24 months, may continue as long as deriving clinical benefit
OR
Dasatinib 72 mg/m² PFSO QD [with a maximum dose of 120 mg QD for subjects with high BSA] for minimum of 24 months, may continue as long as deriving clinical benefit


Treatment: Drugs: Dasatinib


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Major Cytogenetic Response (MCyR) Rate - Major Cytogenetic Response (MCyR) rate is defined as the proportion of all treated participants who achieved a complete (0%) or partial (1%-35% Ph+ metaphases in at least 20 metaphases in bone marrow) cytogenetic response, expressed as percentage. The denominator of the MCyR response rate consists of all treated participants in Cohort 1, and the numerator is all participants in Cohort 1 achieving MCyR. 95% confidence interval was calculated by Clopper-Pearson exact method.
Timepoint [1] 0 0
From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
Primary outcome [2] 0 0
Complete Hematologic Response (CHR) Rate - Complete Hematologic Response (CHR) rate is defined as the proportion of all treated participants who achieve a confirmed CHR while on-study, expressed as percentage. CHR is defined as including no more than 5% blasts in bone marrow and normal white blood cell count without blasts in peripheral blood, expressed as percentage. The denominator of the CHR response rate consists of all treated participants in Cohort 2, and the numerator is all participants in Cohort 2 achieving CHR. 95% confidence interval was calculated by Clopper-Pearson exact method.
Timepoint [2] 0 0
From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
Primary outcome [3] 0 0
Complete Cytogenetic Response (CCyR) Rate - Complete Cytogenetic Response (CCyR) rate is defined as the proportion of all treated participants who achieve a CCyR while on-study, expressed as a percentage. CCyR rate is defined as 0% Ph+ metaphases in at least 20 metaphases in bone marrow. The denominator of the CCyR response rate consists of all treated participants in Cohort 3, and the numerator is all participants in Cohort 3 achieving CCyR. 95% confidence interval was calculated by Clopper-Pearson exact method.
Timepoint [3] 0 0
From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
Secondary outcome [1] 0 0
Major Cytogenetic Response (MCyR) Rate in Cohort 2 - Major Cytogenetic Response (MCyR) rate was defined as the proportion of all treated participants who achieved a complete (0%) or partial (1%-35% Ph+ metaphases in at least 20 metaphases in bone marrow) cytogenetic response. The percentage of treated participants in each arm with MCyR is reported.
Timepoint [1] 0 0
From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
Secondary outcome [2] 0 0
Complete Hematologic Response (CHR) Rate in Cohorts 1 and 3 - Complete Hematologic Response (CHR) rate defined as the proportion of all treated participants who achieve a confirmed CHR while on-study. CHR is defined as including no more than 5% blasts in bone marrow and normal white blood cell count without blasts in peripheral blood. The percentage of treated participants in each arm with CHR is reported.
Timepoint [2] 0 0
From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
Secondary outcome [3] 0 0
Rate of Best Cytogenetic Response - The number of participants achieving their best on-study cytogenetic response was reported as a percentage of all treated participants in that arm.
Timepoint [3] 0 0
From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
Secondary outcome [4] 0 0
Time to Major Cytogenetic Response (MCyR) - Time to MCyR is defined as the time from first dose of dasatinib until the first day MCyR criteria are met, computed only for participants whose best response is MCyR.
Timepoint [4] 0 0
From first dose until MCyR criteria are met (assessed up to September 2016, approximately 90 months)
Secondary outcome [5] 0 0
Duration of Major Cytogenetic Response (MCyR) - Duration of MCyR will be computed from the first day criteria are met for MCyR until the date PD is reported (or treatment is discontinued for PD) or death. Participants who neither discontinue due to PD nor die will be censored on the date of their last hematologic or cytogenetic assessment, whichever comes last.
Timepoint [5] 0 0
From first day criteria are met for MCyR until the date PD is reported or death (assessed up to September 2016, approximately 90 months)
Secondary outcome [6] 0 0
Time to Complete Cytogenetic Response (CCyR) - Time to CCyR is defined as the time from first dose of dasatinib until the first day CCyR criteria are met, computed only for participants whose best response is CCyR.
Timepoint [6] 0 0
From first dose until CCyR criteria are met, assessed up to September 2016 (approximately 90 months)
Secondary outcome [7] 0 0
Duration of Complete Cytogenetic Response (CCyR) - Duration of CCyR will be computed from the first day criteria are met for CCyR until the date PD is reported (or treatment is discontinued for PD) or death. Participants who neither discontinue due to PD nor die will be censored on the date of their last hematologic or cytogenetic assessment, whichever comes last.
Timepoint [7] 0 0
From first day criteria are met for CCyR until the date of progressive disease or death (assessed up to September 2016, approximately 90 months)
Secondary outcome [8] 0 0
Progression-Free Survival (PFS) Rate at 2 Years - PFS is defined as time from the first dosing date until the time PD is first documented by the investigator or death. Participants who die without a reported date of progression will be considered to have progressed on the date of death. Participants who neither progress nor die will be censored on the date of their last cytogenetic or hematologic assessment. The percentages of progression-free participants at 2 years are based on Kaplan-Meier estimation.
Disease Progression was defined as any of the following criteria:
For CP-CML, progression to AP-CML or BP-CML while at highest tolerated dose
Increasing WBC
Loss of CHR (defined as any of the following: WBC count rises to >20.0x10^9/L; Platelet count rises to >600x10^9/L; appearance of extramedullary disease; appearance of >5% myelocytes+metamyelocytes in blood; appearance of blasts/promyelocytes in peripheral blood)
Loss of MCyR or increase in Ph+ bone marrow cells by >=30% from nadir
Death from any case during treatment
Timepoint [8] 0 0
2 years
Secondary outcome [9] 0 0
Time to Complete Hematologic Response (CHR) - Time to CHR is defined as the time from first dose of dasatinib until the first day CHR criteria are met, provided they are confirmed 4 weeks later, computed only for participants whose best response is CHR.
Timepoint [9] 0 0
From first dose until CHR criteria are met, assessed up to September 2016 (approximately 90 months)
Secondary outcome [10] 0 0
Duration of Complete Hematologic Response (CHR) - Duration of CHR will be computed from the first day all criteria are met for CHR, provided they are confirmed 4 weeks later, until the date progressive disease (PD) is reported (or treatment is discontinued for PD) or death. Participants who neither discontinue due to PD nor die will be censored on the date of their last hematologic assessment.
Timepoint [10] 0 0
From first day criteria are met for CHR until date of disease progression or death (assessed up to September 2016, approximately 90 months)
Secondary outcome [11] 0 0
Disease-Free Survival Rate at 2 Years - Disease free survival is defined as time from CCyR for participants with newly diagnosed chronic phase CML and for participants with chronic phase CML who are resistant or intolerant to imatinib (cohort 3 and cohort 1), and as time from CHR for participants with advanced phase CML and PH + ALL (cohort 2) until the time progression is first documented by the investigator or death from any cause. The percentages of disease-free participants at 2 years are based on Kaplan-Meier estimation.
Timepoint [11] 0 0
2 years
Secondary outcome [12] 0 0
Overall Survival (OS) Rate at 2 Years - OS is defined as time from the first dosing date until the time of death. All participants will be followed yearly for survival for up to 5 years after treatment discontinuation. Participants who have not died or who are lost to follow-up will be censored on the last date the participant is known to be alive. The percentages of surviving participants at 2 years are based on Kaplan-Meier estimation.
Timepoint [12] 0 0
2 years
Secondary outcome [13] 0 0
Major Molecular Response (MMR) Rate - Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (qPCR). MMR for participants with the p210 BCR-ABL transcript variant was defined as a ratio BCR-ABL/ABL <= 10-3 or 0.1% on the international scale. In this study, ABL was used as the control-gene. For a participant with the p190 BCR-ABL transcript variant (occurring in Cohort 2 only), on-study assessments were compared to the participant's individual baseline BCR-ABL/ABL ratio and a reduction to < 0.1% or a 3-log reduction from baseline was considered an MMR.
Timepoint [13] 0 0
From date of first treatment to date of MMR (assessed up to September 2016, approximately 90 months)
Secondary outcome [14] 0 0
Complete Molecular Response (CMR) Rate - Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (qPCR). (CMR) is defined as absence of BCR-ABL rearrangements by real-time qPCR analysis. The percentage of treated participants with CMR is reported by arm.
Timepoint [14] 0 0
From date of first treatment to date of CMR (assessed up to September 2016, approximately 90 months)
Secondary outcome [15] 0 0
Major Cytogenetic Response (MCyR) Rate up to 2 Years - Major Cytogenetic Response (MCyR) rate is defined as the proportion of all treated participants who achieved a complete (0%) or partial (1%-35% Ph+ metaphases in at least 20 metaphases in bone marrow) cytogenetic response. The percentage of treated participants with MCyR is reported by arm.
Timepoint [15] 0 0
24 months
Secondary outcome [16] 0 0
Complete Cytogenetic Response (CCyR) Rate up to 2 Years - Complete Cytogenetic Response (CCyR) rate is defined as the proportion of all treated participants who achieve a CCyR while on-study. CCyR rate is defined as 0% Ph+ metaphases in at least 20 metaphases in bone marrow. The percentage of treated participants with CCyR is reported by arm.
Timepoint [16] 0 0
24 months
Secondary outcome [17] 0 0
Major Molecular Response (MMR) Rate up to 2 Years - Molecular response will be assessed using BCR-ABL transcript levels measurement by real-time qPCR. MMR for participants with the p210 BCR-ABL transcript variant is defined according to the recommendations of Hughes et al. as a ratio BCR-ABL/ABL <= 10-3 or 0.1% on the international scale proposed by the authors. The standardized baseline, as established in the IRIS trial, is taken to represent 100% on the international scale and a 3-log reduction in ratio (BCR-ABL transcripts/ABL or BCR) from the standardized baseline (MMR) is fixed at 0.1%. In this study, ABL or other housekeeping gene, will be used as the control-gene. For a participant with the p190 BCR-ABL transcript variant, on-study assessments will be compared to the participant's individual baseline BCR-ABL/ABL ratio and a reduction to < 0.1% or a 3-log reduction from baseline will be considered an MMR. The percentage of treated participants with MMR is reported by arm.
Timepoint [17] 0 0
24 months
Secondary outcome [18] 0 0
Complete Molecular Response (CMR) Rate up to 2 Years - Molecular response will be assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (qPCR). (CMR) is defined as absence of BCR-ABL rearrangements by real-time qPCR analysis. The percentage of treated participants with CMR is reported by arm.
Timepoint [18] 0 0
24 months

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



- 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
Minimum age
No limit
Maximum age
18 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Local Institution - Randwick
Recruitment hospital [2] 0 0
Local Institution - Westmead
Recruitment hospital [3] 0 0
Local Institution - Sth Brisbane
Recruitment hospital [4] 0 0
Local Institution - North Adelaide
Recruitment hospital [5] 0 0
Local Institution - Parkville
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4101 - Sth Brisbane
Recruitment postcode(s) [4] 0 0
5006 - North Adelaide
Recruitment postcode(s) [5] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Oregon
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
Argentina
State/province [12] 0 0
Buenos Aires
Country [13] 0 0
Argentina
State/province [13] 0 0
Cordoba
Country [14] 0 0
Brazil
State/province [14] 0 0
Parana
Country [15] 0 0
Brazil
State/province [15] 0 0
RIO Grande DO SUL
Country [16] 0 0
Brazil
State/province [16] 0 0
Campinas
Country [17] 0 0
Brazil
State/province [17] 0 0
Sao Paulo
Country [18] 0 0
Canada
State/province [18] 0 0
Alberta
Country [19] 0 0
Canada
State/province [19] 0 0
British Columbia
Country [20] 0 0
Canada
State/province [20] 0 0
Nova Scotia
Country [21] 0 0
Canada
State/province [21] 0 0
Ontario
Country [22] 0 0
Canada
State/province [22] 0 0
Quebec
Country [23] 0 0
France
State/province [23] 0 0
Lyon
Country [24] 0 0
France
State/province [24] 0 0
Nantes
Country [25] 0 0
France
State/province [25] 0 0
Paris Cedex 12
Country [26] 0 0
France
State/province [26] 0 0
Paris
Country [27] 0 0
France
State/province [27] 0 0
Poitiers
Country [28] 0 0
Germany
State/province [28] 0 0
Frankfurt
Country [29] 0 0
Germany
State/province [29] 0 0
Hannover
Country [30] 0 0
India
State/province [30] 0 0
Gujarat
Country [31] 0 0
India
State/province [31] 0 0
Karnataka
Country [32] 0 0
India
State/province [32] 0 0
Maharashtra
Country [33] 0 0
India
State/province [33] 0 0
Tamil NADU
Country [34] 0 0
India
State/province [34] 0 0
Tamilnadu
Country [35] 0 0
India
State/province [35] 0 0
Kolkatta
Country [36] 0 0
India
State/province [36] 0 0
Mumbai
Country [37] 0 0
India
State/province [37] 0 0
Trivandrum
Country [38] 0 0
Italy
State/province [38] 0 0
Bologna
Country [39] 0 0
Italy
State/province [39] 0 0
Monza (MB)
Country [40] 0 0
Italy
State/province [40] 0 0
Roma
Country [41] 0 0
Italy
State/province [41] 0 0
Torino
Country [42] 0 0
Korea, Republic of
State/province [42] 0 0
Seoul
Country [43] 0 0
Mexico
State/province [43] 0 0
Distrito Federal
Country [44] 0 0
Mexico
State/province [44] 0 0
Jalisco
Country [45] 0 0
Mexico
State/province [45] 0 0
Nuevo LEON
Country [46] 0 0
Netherlands
State/province [46] 0 0
Rotterdam
Country [47] 0 0
Romania
State/province [47] 0 0
Bucharest
Country [48] 0 0
Russian Federation
State/province [48] 0 0
Moscow
Country [49] 0 0
Russian Federation
State/province [49] 0 0
Saint-petersburg
Country [50] 0 0
Singapore
State/province [50] 0 0
Singapore
Country [51] 0 0
South Africa
State/province [51] 0 0
FREE State
Country [52] 0 0
South Africa
State/province [52] 0 0
Gauteng
Country [53] 0 0
South Africa
State/province [53] 0 0
Western CAPE
Country [54] 0 0
Spain
State/province [54] 0 0
Barcelona
Country [55] 0 0
Spain
State/province [55] 0 0
Madrid
Country [56] 0 0
Spain
State/province [56] 0 0
Malaga
Country [57] 0 0
Spain
State/province [57] 0 0
Valencia
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Central
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Surrey
Country [60] 0 0
United Kingdom
State/province [60] 0 0
WEST Midlands

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/show/NCT00777036
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications