Study of Dasatinib in Children and Adolescents With Relapsed or Refractory Leukemia
Condition: Leukemia
MeSH terms: Leukemia
Intervention: Dasatinib; Dasatinib; Dasatinib
Intervention description: 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).; 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.; 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 MeSH terms: Dasatinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 63.0
Sex: All
Minimum age: 12 Months
Maximum age: 20 Years
Healthy volunteers: No
Keywords: Relapsed and Refractory Leukemia

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.
    

Eligibility criteria:

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