Phase 1
Completed N=58
Study of Dasatinib in Children and Adolescents With Relapsed or Refractory Leukemia
Source: ClinicalTrials.gov NCT00306202 ↗Enrolled (actual)
58
Serious AEs
75.9%
Results posted
Jul 2012
Primary outcomePrimary: Recommended Phase II Dose of Dasatinib in Children and Adolescents With Relapsed or Refractory Leukemia — 60; 80; NA mg/m^2 QD
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Recommended Phase II Dose of Dasatinib in Children and Adolescents With Relapsed or Refractory Leukemia |
60; 80; NA | — |
| SECONDARY Number of Participants With Related Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0. |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Dose-limiting Toxicity (DLT) |
0; 0; 0; 0; 1; 0 | — |
| SECONDARY Number of Participants With Hematology Abnormalities by NCI CTCAE Version 3.0 |
6; 4; 2; 1; 1; 1 | — |
| SECONDARY Number of Participants With Serum Chemistry Abnormalities (Calcium, Magnesium, and Phosphate) by NCI CTCAE Version 3.0 |
3; 0; 2; 2; 2; 0 | — |
| SECONDARY Number of Participants With Serum Chemistry Abnormalities (Liver and Renal Function) by NCI CTCAE Version 3.0 |
1; 3; 5; 3; 1; 4 | — |
| SECONDARY Number of Participants With Major Cytogenetic Response (MCyR) at Any Time in Stratum 1 (Ph+ CP-CML) and Stratum 2/3 (Ph+ ALL or AP/BP-CML) |
9; 6; 4; 7 | — |
| SECONDARY Number of Participants With Major Cytogenetic Response (MCyR) in Stratum 1 (Ph+ CP-CML) Within First 12 and 24 Weeks |
6; 2; 9; 5 | — |
| SECONDARY Best Cytogenetic Response (CyR) in Stratum 1 (Ph+ CP-CML) and Stratum 2/3 (Ph+ ALL or AP/BP-CML) |
1; 0; 0; 1; 0; 0 | — |
| SECONDARY Percentage of Participants With Complete Cytogenetic Response (CCyR) or Major Cytogenetic Response (MCyR) at Recommended Phase II Dose |
72.7; 88.9; 81.8; 88.9 | — |
| SECONDARY Time to Major Cytogenetic Response (MCyR) in Responders: Stratum 1 (Ph+ CP-CML) and Stratum 2/3 (Ph+ ALL or AP/BP-CML) |
75.0; 33.5 | — |
| SECONDARY Duration of Major Cytogenetic Response (MCyR) in Responders (Stratum 1 [Ph+ CP-CML] and Stratum 2/3 [Ph+ ALL or AP/BP-CML]) |
52.2; 4.6 | — |
| SECONDARY Duration of Complete Cytogenetic Response (CCyR) in Responders: Stratum 1 [Ph+ CP-CML] and Stratum 2/3 [Ph+ ALL or AP/BP-CML] |
48.1; 4.6 | — |
| SECONDARY Number of Participants With Major Hematologic Response (MaHR) at Any Time in Stratum 2/3 (Ph+ ALL or AP/BP-CML) and Stratum 4 (Ph- ALL/AML) |
2; 6; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Major Hematologic Response (MaHR) in Stratum 2/3 (Ph+ ALL or AP/BP-CML) Within First 6 and 24 Weeks |
2; 5; 2; 6 | — |
| SECONDARY Best Hematologic Response (HR) At Any Time: Stratum 1 (Ph+ CP-CML) |
10; 6; 1; 0; 10; 6 | — |
| SECONDARY Best Hematologic Response (HR) At Any Time: Stratum 2/3 (Ph+ ALL or AP/BP-CML) |
1; 5; 1; 1; 6; 3 | — |
| SECONDARY Best Hematologic Response (HR) At Any Time: Stratum 4 (Ph- ALL/AML) |
5; 6; 6; 6; 1; 0 | — |
| SECONDARY Time to Major Hematologic Response (MaHR): Stratum 2/3 (PH+ ALL or AP/BP-CML) |
36.0 | — |
| SECONDARY Time to Complete Hematologic Response (CHR): Stratum 1 (Ph+ CP-CML) and Stratum 2/3 (Ph+ALL or AP/BP-CML) |
21.5; 39.5 | — |
| SECONDARY Duration of Major Hematologic Response (MaHR): Stratum 2/3 (Ph+ALL or AP/BP-CML) |
4.4 | — |
| SECONDARY Duration of Complete Hematologic Response (CHR): Stratum 1 (Ph+ CP-CML) and Stratum 2/3 (Ph+ALL or AP/BP-CML) |
NA; 7.3 | — |
| SECONDARY Percentage of Participants With Confirmed Hematologic Response (HR) at Recommended Phase II Dose: Stratum 1 (Ph+ CP-CML) |
90.9 | — |
| SECONDARY Percentage of Participants With Confirmed Hematologic Response (HR) at Recommended Phase II Dose: Stratum 2/3 (Ph+ALL or AP/BP-CML) |
55.6; 66.7; 66.7 | — |
| SECONDARY Number of Participants With Molecular Responses in Stratum 1 (Ph+ CP-CML) |
6; 2; 3; 1; 1; 0 | — |
| SECONDARY Number of Participants With Major Molecular Response (MMR) in Stratum 2/3 (Ph+ ALL or AP/BP-CML) |
2; 6 | — |
| SECONDARY Progression Free Survival (PFS) |
53.6; 4.9; 1.4 | — |
| SECONDARY Overall Survival (OS) |
NA; 8.6; 3.0 | — |
| SECONDARY Dasatinib Plasma Pharmacokinetic (PK) Parameter: Time to Achieve the Observed Maximum Plasma Concentration (Tmax) by Age Group |
0.5; 1.1; 1.0; 0.9; 1.0 | — |
| SECONDARY Dasatinib Plasma Pharmacokinetic Parameter: Terminal Half-life (T 1/2) by Age Group |
2.1; 3.0; 3.8; 7.3; 3.3 | — |
| SECONDARY Dasatinib Plasma Pharmacokinetic Parameter: Dose Normalized Observed Maximum Plasma Concentration (Cmax) by Age Group |
1.0; 1.9; 1.0; 0.9; 1.5 | — |
| SECONDARY Dasatinib Plasma Pharmacokinetic Parameter: Dose Normalized Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-T]) by Age Group |
2.8; 6.1; 3.8; 2.2; 4.9 | — |
| SECONDARY Dasatinib Plasma Pharmacokinetic Parameter: Dose Normalized Area Under the Plasma Concentration Versus Time Curve From Time Zero Extrapolated to Infinite Time (AUC[INF]) by Age Group |
3.2; 6.7; 4.2; 2.4; 5.4 | — |
| SECONDARY Dasatinib Plasma Pharmacokinetic Parameter: Observed Maximum Plasma Concentration (Cmax) by Dose Level and Age Group |
NA; NA; 30.6; 53.8; 110.6; 142.5 | — |
| SECONDARY Dasatinib Plasma Pharmacokinetic (PK) Parameter: Time to Achieve the Observed Maximum Plasma Concentration (Tmax) By Dose Level and Age Group |
NA; NA; 0.5; 0.5; 1.1; 1.5 | — |
| SECONDARY Dasatinib Plasma Pharmacokinetic Parameter: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-T]) by Dose Level and Age Group |
NA; NA; 100.8; 134.9; 295.0; 490.8 | — |
| SECONDARY Dasatinib Plasma Pharmacokinetic Parameter: Area Under the Plasma Concentration Versus Time Curve From Time Zero Extrapolated to Infinite Time (AUC[INF]) by Dose Level and Age Group |
0; 0; 127.7; 142.1; 313.9; 513.6 | — |
| SECONDARY Dasatinib Plasma Pharmacokinetic Parameter: Terminal Half-life (T 1/2) by Dose Level and Age Group |
NA; NA; 2.5; 1.8; 2.4; 3.9 | — |
| SECONDARY Dasatinib Metabolite (BMS-582691) Plasma Pharmacokinetic Parameter: Observed Maximum Plasma Concentration (Cmax) by Dose Level and Age Group |
NA; NA; NA; 1.2; 3.6; 3.4 | — |
| SECONDARY Dasatinib Metabolite (BMS-582691) Plasma Pharmacokinetic (PK) Parameter: Time to Achieve the Observed Maximum Plasma Concentration (Tmax) By Dose Level and Age Group |
NA; NA; NA; 0.9; 2.0; 2.0 | — |
| SECONDARY Dasatinib Metabolite (BMS-582691) Plasma Pharmacokinetic Parameter: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-T]) by Dose Level and Age Group |
NA; NA; NA; 1.9; 8.8; 16.6 | — |
| SECONDARY Concentration of Dasatinib in Cerebrospinal Fluid (CSF) by Dose Level and Age Group |
1.1; 1.5; 1.7; 3.8; 1.1; 1.0 | — |
| SECONDARY Number of Participants With BCR-ABL Mutations at Baseline: Stratum1 Ph+ CP-CML and Stratum 2/3 Ph+ALL or AP/BP-CML |
1; 0; 1; 0; 0; 1 | — |
| SECONDARY Number of Participants With BCR-ABL Mutations at End-of-Treatment: Stratum1 Ph+ CP-CML and Stratum2/3 Ph+ ALL or AP/BP-CML |
0; 4; 8; 9; 9; 4 | — |
| SECONDARY Number of Participants With FLT3 and KIT Mutations in Stratum4 Ph- ALL/AML at Baseline |
20; 1; 3; 21; 0; 3 | — |
| SECONDARY Number of Participants With FLT3 and KIT Mutations in Stratum4 Ph- ALL/AML at End-Of-Treatment |
6; 0; 18; 6; 0; 18 | — |
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 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.
Data sourced from ClinicalTrials.gov (NCT00306202). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.