Study of Dasatinib in Children and Adolescents With Relapsed or Refractory Leukemia

NCT ID: NCT00306202

Last Updated: 2021-02-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-03-31
• Study Completion Date: 2019-05-22

Brief Summary

The purpose of this clinical research study was to establish a recommended phase 2 once daily (QD) dose of dasatinib and to assess the efficacy of the investigational drug for relapsed or refractory (resistant to previous treatment) leukemia in children and adolescents. The side effects that this oral investigational drug may have in children, and the levels of the drug in the blood, will be studied at different doses.

Conditions

Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Stratum 1 (Ph+ CP-CML)

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP)

Group Type: EXPERIMENTAL

Dasatinib

Intervention Type: DRUG

Tablets, Oral, If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice). Starting Dose Level of 60 mg/m^2; Escalated/Dose Level 2 of 80 mg/m^2. Once daily (QD), as long as clinical benefit was maintained.

Intra-participant dose escalation was allowed based on tolerance and on individual response. The starting dose for subsequent participants in a stratum may have been escalated depending on safety, assessed by prior intra-participant dose-escalation, and lack of efficacy in previous participants. Treatment courses were defined as 3 weeks (21 days plus any required delay); for participants who stayed on treatment > 12 months, courses after 12 months were defined in quartiles of 13 weeks. Participants were to be followed until death or up to 5 years after end-of-treatment (EOT).

Stratum 2/3 (Ph+ ALL or AP/BP-CML)

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML)

Group Type: EXPERIMENTAL

Dasatinib

Intervention Type: DRUG

Tablets, Oral, If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice). Starting Dose Level of 60 mg/m^2; Escalated/Dose Level 2 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Intra-participant dose escalation was allowed based on tolerance and on individual response. The starting dose for subsequent participants in a stratum may have been escalated depending on safety, assessed by prior intra-participant dose-escalation, and lack of efficacy in previous participants. Treatment courses were defined as 3 weeks (21 days plus any required delay); for participants who stayed on treatment > 12 months, courses after 12 months were defined in quartiles of 13 weeks. Participants were to be followed until death or up to 5 years after EOT.

Stratum 4 (Ph- ALL/AML)

Participants with second or subsequent relapse of Ph- ALL or Ph- AML

Group Type: EXPERIMENTAL

Dasatinib

Intervention Type: DRUG

Tablets, Oral, If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice). Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2, Escalated/Dose level 3 of 100 mg/m^2, and Escalated/Dose level 4 of 120 mg/m^2. QD, as long as clinical benefit was maintained.

Intra-participant dose escalation was allowed based on tolerance and on individual response. The starting dose for subsequent participants in a stratum may have been escalated depending on safety, assessed by prior intra-participant dose-escalation, and lack of efficacy in previous participants. Treatment courses were defined as 3 weeks (21 days plus any required delay); for participants who stayed on treatment > 12 months, courses after 12 months were defined in quartiles of 13 weeks. Participants were to be followed until death or up to 5 years after EOT.

Interventions

Dasatinib

Tablets, Oral, If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice). Starting Dose Level of 60 mg/m^2; Escalated/Dose Level 2 of 80 mg/m^2. Once daily (QD), as long as clinical benefit was maintained.

Intra-participant dose escalation was allowed based on tolerance and on individual response. The starting dose for subsequent participants in a stratum may have been escalated depending on safety, assessed by prior intra-participant dose-escalation, and lack of efficacy in previous participants. Treatment courses were defined as 3 weeks (21 days plus any required delay); for participants who stayed on treatment > 12 months, courses after 12 months were defined in quartiles of 13 weeks. Participants were to be followed until death or up to 5 years after end-of-treatment (EOT).

Intervention Type: DRUG

Dasatinib

Tablets, Oral, If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice). Starting Dose Level of 60 mg/m^2; Escalated/Dose Level 2 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Intra-participant dose escalation was allowed based on tolerance and on individual response. The starting dose for subsequent participants in a stratum may have been escalated depending on safety, assessed by prior intra-participant dose-escalation, and lack of efficacy in previous participants. Treatment courses were defined as 3 weeks (21 days plus any required delay); for participants who stayed on treatment > 12 months, courses after 12 months were defined in quartiles of 13 weeks. Participants were to be followed until death or up to 5 years after EOT.

Intervention Type: DRUG

Dasatinib

Tablets, Oral, If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice). Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2, Escalated/Dose level 3 of 100 mg/m^2, and Escalated/Dose level 4 of 120 mg/m^2. QD, as long as clinical benefit was maintained.

Intra-participant dose escalation was allowed based on tolerance and on individual response. The starting dose for subsequent participants in a stratum may have been escalated depending on safety, assessed by prior intra-participant dose-escalation, and lack of efficacy in previous participants. Treatment courses were defined as 3 weeks (21 days plus any required delay); for participants who stayed on treatment > 12 months, courses after 12 months were defined in quartiles of 13 weeks. Participants were to be followed until death or up to 5 years after EOT.

Intervention Type: DRUG

Other Intervention Names

Sprycel; BMS-354825; Sprycel; BMS-354825; Sprycel; BMS-354825

Eligibility Criteria

Inclusion Criteria

• Ph-positive (Ph+) Chronic Myelogenous Leukemia in chronic, accelerated or blast phase or Ph+ acute lymphoblastic leukemia (ALL) with imatinib-resistant disease or intolerance to imatinib.
• Ph-negative acute leukemia in second or subsequent relapse
• Age >1 and <21 years
• Lansky or Karnofsky scale >60
• Life expectancy >3 weeks
• Adequate hepatic and renal function
• Written informed consent

Exclusion Criteria

• Subjects for whom potentially-curative therapy was available, including electing immediate [ie, planned <45 days] stem-cell transplantation. Subjects in Stratum 1 were to have had an ongoing identical HLA donor search, and may have discontinued study if a donor became available.)
• Subjects with symptomatic central nervous system (CNS) disease (eg, convulsions due to their CNS disease).
• Subjects who had not recovered from acute toxicity of previous therapy.
• Clinically-significant disorder of platelet function (eg, von Willebrand's disease) or ongoing gastrointestinal bleeding.
• Serious uncontrolled medical disorder or active infection
• Uncontrolled or significant cardiovascular disease
• Use of any investigational agent or any other anticancer agent within 14 days prior to treatment start.
• Prior therapy with dasatinib
• Subjects taking medications that irreversibly inhibit platelet function or anticoagulants.
• Subjects taking certain medications that are accepted to have a risk of causing QTc prolongation.
• Women of Child Bearing Potential with a positive pregnancy test prior to study drug administration.
• Expected noncompliance, or unable to have regular follow-up due to psychologic, social, familial, or geographic reasons.
• Subjects who are compulsorily detained for legal reasons or treatment of either a psychiatric or physical (eg, infectious disease) illness must not be enrolled into this study.

• Minimum Eligible Age: 12 Months
• Maximum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Innovative Therapies For Children with Cancer Consortium

OTHER

Sponsor Role: collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Local Institution

Vienna, , Austria

Local Institution

Nantes, , France

Local Institution

Paris, , France

Local Institution

Paris, , France

Local Institution

Berlin, , Germany

Local Institution

Frankfurt, , Germany

Local Institution

Hanover, , Germany

Local Institution

Monza (mi), , Italy

Local Institution

Rotterdam, , Netherlands

Local Institution

Manchester, Greater Manchester, United Kingdom

Local Institution

Bristol, Somerset, United Kingdom

Local Institution

Sutton, Surrey, United Kingdom

Local Institution

Birmingham, West Midlands, United Kingdom

Countries

Austria; France; Germany; Italy; Netherlands; United Kingdom

References

Zwaan CM, Rizzari C, Mechinaud F, Lancaster DL, Lehrnbecher T, van der Velden VH, Beverloo BB, den Boer ML, Pieters R, Reinhardt D, Dworzak M, Rosenberg J, Manos G, Agrawal S, Strauss L, Baruchel A, Kearns PR. Dasatinib in children and adolescents with relapsed or refractory leukemia: results of the CA180-018 phase I dose-escalation study of the Innovative Therapies for Children with Cancer Consortium. J Clin Oncol. 2013 Jul 1;31(19):2460-8. doi: 10.1200/JCO.2012.46.8280. Epub 2013 May 28.

Reference Type: DERIVED

PMID: 23715577 (View on PubMed)

Related Links

http://www.bms.com/studyconnect/Pages/home.aspx

BMS clinical trial educational resource

http://www.bms.com/clinical_trials/Pages/Investigator_Inquiry_form.aspx

Investigator Inquiry form

Other Identifiers

Protocol ITCC 005

Identifier Type: -

Identifier Source: secondary_id

2005-002882-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CA180-018

Identifier Type: -

Identifier Source: org_study_id