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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00777036
• Other study ID #: CA180-226
• Secondary ID: 2008-002260-33
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 20, 2009
• Est. completion date: December 7, 2029

Study information

• Verified date: August 2023
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 130
• Est. completion date: December 7, 2029
• Est. primary completion date: September 1, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 18 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Dasatinib

Locations

Country	Name	City	State
Argentina	Local Institution	Bunos Aires	Buenos Aires
Argentina	Local Institution - 0043	Bunos Aires	Buenos Aires
Argentina	Local Institution	Cordoba
Argentina	Local Institution - 0042	Cordoba
Argentina	Hospital Nacional Profesor Alejandro Posadas	El Palomar	Buenos Aires
Argentina	Local Institution - 0049	El Palomar	Buenos Aires
Australia	Local Institution	North Adelaide	South Australia
Australia	Local Institution - 067	North Adelaide	South Australia
Australia	Local Institution	Parkville	Victoria
Australia	Local Institution - 0066	Parkville	Victoria
Australia	Local Institution	Randwick	New South Wales
Australia	Local Institution - 065	Randwick	New South Wales
Australia	Local Institution	Sth Brisbane	Queensland
Australia	Local Institution - 0064	Sth Brisbane	Queensland
Australia	Local Institution	Westmead	New South Wales
Australia	Local Institution - 069	Westmead	New South Wales
Brazil	Local Institution	Campinas
Brazil	Local Institution - 0020	Campinas
Brazil	Local Institution	Curitiba	Parana
Brazil	Local Institution - 0021	Curitiba	Parana
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution - 0022	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Sao Paulo
Brazil	Local Institution	Sao Paulo
Brazil	Local Institution - 0039	Sao Paulo
Brazil	Local Institution - 0019	São Paulo	SAO Paulo
Canada	Alberta Children'S Hospital	Calgary	Alberta
Canada	Local Institution - 0079	Calgary	Alberta
Canada	Local Institution - 0078	Edmonton	Alberta
Canada	Stollery Children'S Hospital	Edmonton	Alberta
Canada	Iwk Health Centre	Halifax	Nova Scotia
Canada	Local Institution - 073	Halifax	Nova Scotia
Canada	Chu Ste-Justine	Montreal	Quebec
Canada	Local Institution - 080	Montreal	Quebec
Canada	Children'S Hospital Of Eastern Ontario	Ottawa	Ontario
Canada	Local Institution - 086	Ottawa	Ontario
Canada	Local Institution - 076	Toronto	Ontario
Canada	The Hospital For Sick Children	Toronto	Ontario
Canada	Bc Children'S Hospital	Vancouver	British Columbia
Canada	Local Institution - 077	Vancouver	British Columbia
France	Local Institution	Lyon
France	Local Institution - 0030	Lyon
France	Local Institution	Nantes
France	Local Institution - 0032	Nantes
France	Local Institution	Paris
France	Local Institution	Paris
France	Local Institution - 0029	Paris
France	Local Institution - 0037	Paris
France	Local Institution	Paris Cedex 12
France	Local Institution	Poitiers
France	Local Institution - 036	Poitiers
Germany	Local Institution	Frankfurt
Germany	Local Institution - 075	Frankfurt
Germany	Local Institution	Hannover
Germany	Local Institution - 0074	Hannover
India	Local Institution	Bangalore	Karnataka
India	Local Institution - 0088	Bangalore
India	Local Institution	Kolkatta
India	Local Institution - 0082	Kolkatta
India	Local Institution	Madurai	Tamil Nadu
India	Local Institution - 0093	Madurai	Tamil Nadu
India	Local Institution	Mumbai
India	Local Institution	Mumbai	Maharashtra
India	Local Institution - 0085	Mumbai
India	Local Institution	Navrangpura, Ahmedabad	Gujarat
India	Local Institution - 0089	Navrangpura, Ahmedabad	Gujarat
India	Local Institution	Pune	Maharashtra
India	Local Institution - 0094	Pune	Maharashtra
India	Local Institution	Trivandrum
India	Local Institution - 0084	Trivandrum
India	Local Institution	Vellore	Tamilnadu
Italy	Local Institution	Bologna
Italy	Local Institution - 038	Bologna
Italy	Local Institution - 006	Monza
Italy	Local Institution	Monza (MB)
Italy	Local Institution	Roma
Italy	Local Institution	Roma
Italy	Local Institution - 0059	Roma
Italy	Local Institution - 070	Roma
Italy	Local Institution	Torino
Italy	Local Institution - 015	Torino
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution - 0091	Seoul
Korea, Republic of	Local Institution - 0092	Seoul
Mexico	Local Institution - 0051	Cuauhtémoc	Distrito Federal
Mexico	Local Institution	Df	Distrito Federal
Mexico	Hospital Civil De Guadalajara - Nuevo Dr. Juan I. Menchaca	Guadalajara	Jalisco
Mexico	Local Institution - 0054	Guadalajara	Jalisco
Mexico	Local Institution	Mexico	Distrito Federal
Mexico	Local Institution - 0053	Mexico	Distrito Federal
Mexico	Local Institution	Mexico D.f.	Distrito Federal
Mexico	Local Institution - 0052	Mexico D.f.	Distrito Federal
Mexico	Local Institution	Mexico, D. F.	Distrito Federal
Mexico	Local Institution	Monterrey	Nuevo Leon
Mexico	Local Institution - 0050	Monterrey	Nuevo Leon
Mexico	Local Institution	Monterrey, N.l.	Nuevo Leon
Mexico	Local Institution - 0060	Monterrey, N.l.	Nuevo Leon
Netherlands	Local Institution	Rotterdam
Netherlands	Local Institution - 0007	Rotterdam
Netherlands	Local Institution - 0099	Utrecht
Romania	Local Institution	Bucharest
Romania	Local Institution - 0095	Bucharest
Romania	Local Institution - 0097	Sector 2
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution - 0017	Moscow
Russian Federation	Local Institution - 0023	Moscow
Russian Federation	Local Institution	Saint-petersburg
Russian Federation	Local Institution - 0018	Saint-petersburg
Singapore	Local Institution	Singapore
Singapore	Local Institution - 0071	Singapore
South Africa	Local Institution	Bloemfontein	FREE State
South Africa	Local Institution - 0055	Bloemfontein	FREE State
South Africa	Local Institution	Cape Town	Western CAPE
South Africa	Local Institution - 0057	Cape Town	Western CAPE
South Africa	Local Institution	Pretoria	Gauteng
South Africa	Local Institution - 058	Pretoria	Gauteng
South Africa	Local Institution	Tygerberg	Western CAPE
South Africa	Local Institution - 062	Tygerberg	Western CAPE
Spain	Local Institution	Barcelona
Spain	Local Institution	Barcelona
Spain	Local Institution - 0012	Barcelona
Spain	Local Institution - 0013	Barcelona
Spain	Local Institution	Madrid
Spain	Local Institution	Madrid
Spain	Local Institution - 0010	Madrid
Spain	Local Institution - 0011	Madrid
Spain	Local Institution	Malaga
Spain	Local Institution - 0041	Malaga
Spain	Local Institution	Valencia
Spain	Local Institution	Valencia
Spain	Local Institution - 0033	Valencia
United Kingdom	Local Institution	Birmingham	West Midlands
United Kingdom	Local Institution - 0008	Birmingham	West Midlands
United Kingdom	Local Institution	Glasgow	Central
United Kingdom	Local Institution - 0016	Glasgow	Central
United Kingdom	Local Institution	Sutton	Surrey
United Kingdom	Local Institution - 0009	Sutton	Surrey
United States	Children's Healthcare Of Atlanta - Egleston	Atlanta	Georgia
United States	Children's Healthcare of Atlanta - Egleston Hospital	Atlanta	Georgia
United States	Children'S Hospital	Aurora	Colorado
United States	Local Institution - 0004	Aurora	Colorado
United States	Local Institution	Birmingham	Alabama
United States	Dana Faber Cancer Institute	Boston	Massachusetts
United States	Dana Farber Cancer Institute.	Boston	Massachusetts
United States	Local Institution - 0040	Boston	Massachusetts
United States	Children's Hospital of Chicago	Chicago	Illinois
United States	Local Institution	Chicago	Illinois
United States	Local Institution - 0072	Chicago	Illinois
United States	Local Institution - 0035	Houston	Texas
United States	Local Institution - 0048	Houston	Texas
United States	MD Anderson Cancer Center	Houston	Texas
United States	Texas Children'S Cancer Center	Houston	Texas
United States	Jonathan Jaques Children'S Cancer Center	Long Beach	California
United States	Jonathan Jaques Children'S Cancer Center	Long Beach	California
United States	Local Institution - 0001	Long Beach	California
United States	Local Institution - 0061	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering Nassau	New York	New York
United States	Stephen D. Hassenfeld Children'S Center	New York	New York
United States	Children'S Hospital Of Orange County	Orange	California
United States	Local Institution - 0024	Orange	California
United States	Children'S Hospital Of Philadelphia	Philadelphia	Pennsylvania
United States	Local Institution - 0014	Philadelphia	Pennsylvania
United States	Local Institution - 0005	Phoenix	Arizona
United States	Phoenix Children'S Hospital	Phoenix	Arizona
United States	Children'S Hospital Of Pittsburgh	Pittsburgh	Pennsylvania
United States	Local Institution - 0003	Pittsburgh	Pennsylvania
United States	Local Institution - 0002	Portland	Oregon
United States	Oregon Health & Sci Univ	Portland	Oregon
United States	Oregon Health & Sci Univ	Portland	Oregon
United States	Local Institution - 0028	Seattle	Washington
United States	Seattle Children'S	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  France,  Germany,  India,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Romania,  Russian Federation,  Singapore,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
Primary	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.	From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
Primary	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.	From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
Secondary	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.	From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
Secondary	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.	From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
Secondary	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. (Based on >=20 Metaphases)	From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
Secondary	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. (Based on >=20 Metaphases)	From first dose until MCyR criteria are met (assessed up to September 2016, approximately 90 months)
Secondary	Duration of Major Cytogenetic Response (MCyR)	Duration of MCyR will be computed from the first day criteria are met for MCyR 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 or cytogenetic assessment, whichever comes last. (Based on >=20 Metaphases)	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	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. (Based on >=20 Metaphases)	From first dose until CCyR criteria are met, assessed up to September 2016 (approximately 90 months)
Secondary	Duration of Complete Cytogenetic Response (CCyR)	Duration of CCyR will be computed from the first day criteria are met for CCyR 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 or cytogenetic assessment, whichever comes last. (Based on >=20 Metaphases)	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	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	2 years
Secondary	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.	From first dose until CHR criteria are met, assessed up to September 2016 (approximately 90 months)
Secondary	Duration of Complete Hemotologic 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.	From first day criteria are met for CHR until date of disease progression or death (assessed up to September 2016, approximately 90 months)
Secondary	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. (CML: Chronic Myeloid Leukemia)	2 years
Secondary	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.	2 years
Secondary	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.	From date of first treatment to date of MMR (assessed up to September 2016, approximately 90 months)
Secondary	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.	From date of first treatment to date of CMR (assessed up to September 2016, approximately 90 months)
Secondary	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.	24 months
Secondary	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.	24 months
Secondary	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.	24 months
Secondary	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.	24 months

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting