TriangleNCT00306202 · CITED IN SOURCE DOCUMENTS
Study of Dasatinib in Children and Adolescents With Relapsed or Refractory Leukemia
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE1
- Status at capture
- COMPLETED
- Registry last update
- 2021-02-26
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.
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What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Recommended Phase II Dose of Dasatinib in Children and Adolescents With Relapsed or Refractory Leukemia
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.
Number of Participants With Dose-limiting Toxicity (DLT)
Number of Participants With Hematology Abnormalities by NCI CTCAE Version 3.0
Number of Participants With Serum Chemistry Abnormalities (Calcium, Magnesium, and Phosphate) by NCI CTCAE Version 3.0
Number of Participants With Serum Chemistry Abnormalities (Liver and Renal Function) by NCI CTCAE Version 3.0
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)
Number of Participants With Major Cytogenetic Response (MCyR) in Stratum 1 (Ph+ CP-CML) Within First 12 and 24 Weeks
Best Cytogenetic Response (CyR) in Stratum 1 (Ph+ CP-CML) and Stratum 2/3 (Ph+ ALL or AP/BP-CML)
Percentage of Participants With Complete Cytogenetic Response (CCyR) or Major Cytogenetic Response (MCyR) at Recommended Phase II Dose
Time to Major Cytogenetic Response (MCyR) in Responders: Stratum 1 (Ph+ CP-CML) and Stratum 2/3 (Ph+ ALL or AP/BP-CML)
Duration of Major Cytogenetic Response (MCyR) in Responders (Stratum 1 [Ph+ CP-CML] and Stratum 2/3 [Ph+ ALL or AP/BP-CML])
Duration of Complete Cytogenetic Response (CCyR) in Responders: Stratum 1 [Ph+ CP-CML] and Stratum 2/3 [Ph+ ALL or AP/BP-CML]
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)
Number of Participants With Major Hematologic Response (MaHR) in Stratum 2/3 (Ph+ ALL or AP/BP-CML) Within First 6 and 24 Weeks
Best Hematologic Response (HR) At Any Time: Stratum 1 (Ph+ CP-CML)
Best Hematologic Response (HR) At Any Time: Stratum 2/3 (Ph+ ALL or AP/BP-CML)
Best Hematologic Response (HR) At Any Time: Stratum 4 (Ph- ALL/AML)
Time to Major Hematologic Response (MaHR): Stratum 2/3 (PH+ ALL or AP/BP-CML)
Time to Complete Hematologic Response (CHR): Stratum 1 (Ph+ CP-CML) and Stratum 2/3 (Ph+ALL or AP/BP-CML)
Duration of Major Hematologic Response (MaHR): Stratum 2/3 (Ph+ALL or AP/BP-CML)
Duration of Complete Hematologic Response (CHR): Stratum 1 (Ph+ CP-CML) and Stratum 2/3 (Ph+ALL or AP/BP-CML)
Percentage of Participants With Confirmed Hematologic Response (HR) at Recommended Phase II Dose: Stratum 1 (Ph+ CP-CML)
Percentage of Participants With Confirmed Hematologic Response (HR) at Recommended Phase II Dose: Stratum 2/3 (Ph+ALL or AP/BP-CML)
Number of Participants With Molecular Responses in Stratum 1 (Ph+ CP-CML)
Number of Participants With Major Molecular Response (MMR) in Stratum 2/3 (Ph+ ALL or AP/BP-CML)
Progression Free Survival (PFS)
Overall Survival (OS)
Dasatinib Plasma Pharmacokinetic (PK) Parameter: Time to Achieve the Observed Maximum Plasma Concentration (Tmax) by Age Group
Dasatinib Plasma Pharmacokinetic Parameter: Terminal Half-life (T 1/2) by Age Group
Dasatinib Plasma Pharmacokinetic Parameter: Dose Normalized Observed Maximum Plasma Concentration (Cmax) by Age Group
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
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
Dasatinib Plasma Pharmacokinetic Parameter: Observed Maximum Plasma Concentration (Cmax) by Dose Level and Age Group
Dasatinib Plasma Pharmacokinetic (PK) Parameter: Time to Achieve the Observed Maximum Plasma Concentration (Tmax) By Dose Level and Age Group
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
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
Dasatinib Plasma Pharmacokinetic Parameter: Terminal Half-life (T 1/2) by Dose Level and Age Group
Dasatinib Metabolite (BMS-582691) Plasma Pharmacokinetic Parameter: Observed Maximum Plasma Concentration (Cmax) by Dose Level and Age Group
Dasatinib Metabolite (BMS-582691) Plasma Pharmacokinetic (PK) Parameter: Time to Achieve the Observed Maximum Plasma Concentration (Tmax) By Dose Level and Age Group
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
Concentration of Dasatinib in Cerebrospinal Fluid (CSF) by Dose Level and Age Group
Number of Participants With BCR-ABL Mutations at Baseline: Stratum1 Ph+ CP-CML and Stratum 2/3 Ph+ALL or AP/BP-CML
Number of Participants With Hematologic Toxicity at Baseline by NCI CTCAE Version 3.0
Number of Participants With Serum Chemistry Abnormalities (Liver and Renal Function) at Baseline by NCI CTCAE Version 3.0
Number of Participants With Serum Chemistry Abnormalities (Calcium, Magnesium, and Phosphate) at Baseline by NCI CTCAE Version 3.0
Number of Participants With BCR-ABL Mutations at End-of-Treatment: Stratum1 Ph+ CP-CML and Stratum2/3 Ph+ ALL or AP/BP-CML
Number of Participants With FLT3 and KIT Mutations in Stratum4 Ph- ALL/AML at Baseline
Number of Participants With FLT3 and KIT Mutations in Stratum4 Ph- ALL/AML at End-Of-Treatment
Adverse events
Limitations, agreements, and source contact
Who could take part
- 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.
- healthy Volunteers
- false
- maximum Age
- 20 Years
- minimum Age
- 12 Months
- sex
- ALL
- std Ages
- CHILD
- ADULT
Treatment arms and interventions
- arm Groups
- description
- Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP)
- intervention Names
- Drug: Dasatinib
- label
- Stratum 1 (Ph+ CP-CML)
- type
- EXPERIMENTAL
- description
- 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)
- intervention Names
- Drug: Dasatinib
- label
- Stratum 2/3 (Ph+ ALL or AP/BP-CML)
- type
- EXPERIMENTAL
- description
- Participants with second or subsequent relapse of Ph- ALL or Ph- AML
- intervention Names
- Drug: Dasatinib
- label
- Stratum 4 (Ph- ALL/AML)
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Stratum 1 (Ph+ CP-CML)
- 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).
- name
- Dasatinib
- other Names
- Sprycel
- BMS-354825
- type
- DRUG
- arm Group Labels
- Stratum 2/3 (Ph+ ALL or AP/BP-CML)
- 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. 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.
- name
- Dasatinib
- other Names
- Sprycel
- BMS-354825
- type
- DRUG
- arm Group Labels
- Stratum 4 (Ph- ALL/AML)
- 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, 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.
- name
- Dasatinib
- other Names
- Sprycel
- BMS-354825
- type
- DRUG
Study design
- allocation
- NON_RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 63
- type
- ACTUAL
Registered outcome plans (not posted results)
- other Outcomes
- description
- GR1=Mild; GR2=Moderate; GR3=Severe; GR4=Life-threatening or disabling. Normal ranges provided by local laboratory and may also vary from site to site. White Blood Cell (WBC):GR1=\<LLN-3.0\*10\^9/L; GR2=\<3.0-2.0\*10\^9/L; GR3=\<2.0-1.0\*10\^9/L; GR4=\<1.0\*10\^9/L. Absolute Neutrophil Count (ANC): GR1=\<LLN-1.5\*10\^9 /L; GR2=\<1.5-1.0\*10\^9/L; GR3=\<1.0-0.5\*10\^9/L; GR4=\<0.5\*10\^9/L. Hemoglobin: GR1=\<LLN-10.0g/dL; GR2=\<10.0-8.0g/dL; GR3=\<8.0-6.5g/dL; GR4=\<6.5g/dL. Platelets: GR1=\<LLN-75.0\*10\^9/L; GR2=\<75.0-50.0\*10\^9/L; GR3=\<50.0-25.0\*10\^9/L; GR4=\<25.0\*10\^9/L. LLN=lower limit of normal.
- measure
- Number of Participants With Hematologic Toxicity at Baseline by NCI CTCAE Version 3.0
- time Frame
- At baseline (within 1 week before initiation of study therapy)
- description
- GR1=Mild; GR2=Moderate; GR3=Severe; GR4=Life-threatening or disabling. Normal ranges provided by local laboratory and may also vary from site to site. Aspartate aminotransferase (AST) and alanine aminotransferase(ALT): GR1=\>ULN-2.5\*ULN; GR2=\>2.5-5.0\*ULN; GR3=\>5.0-20.0\*ULN; GR4=\>20.0\*ULN. Total bilirubin:GR1=\>ULN-1.5\*ULN, GR2=\>1.5-3.0\*ULN, GR3=\>3-10\*ULN, GR4=\>10\*ULN. Creatinine: GR1=\>ULN-1.5\*ULN, GR2=\>1.5-3.0\*ULN, GR3=\>3.0-6.0\*ULN, GR4=\>6.0\*ULN. ULN=upper limit of normal.
- measure
- Number of Participants With Serum Chemistry Abnormalities (Liver and Renal Function) at Baseline by NCI CTCAE Version 3.0
- time Frame
- At baseline (within 1 week before initiation of study therapy)
- description
- GR1=Mild; GR2=Moderate; GR3=Severe; GR4=Life-threatening or disabling. Normal ranges provided by local laboratory and may also vary from site to site. Low calcium: GR1=\<LLN-8.0 mg/dL, GR2=\<8.0-7.0 mg/dL, GR3=\<7.0-6.0 mg/dL, GR4=\<6.0 mg/dL; Low magnesium: GR1=\<LLN-1.2 mg/dL, GR2=\<1.2-0.9 mg/dL, GR3=\<0.9-0.7 mg/dL, GR4=\<0.7 mg/dL; Low phosphate: GR1=\<LLN - 2.5 mg/dL, GR2=\<2.5 - 2.0 mg/dL, GR3=\<2.0 - 1.0 mg/dL, GR4=\<1.0 mg/dL.
- measure
- Number of Participants With Serum Chemistry Abnormalities (Calcium, Magnesium, and Phosphate) at Baseline by NCI CTCAE Version 3.0
- time Frame
- At baseline (within 1 week before initiation of study therapy)
- primary Outcomes
- description
- The recommended phase 2 dasatinib dose was determined based on efficacy, safety, and pharmacokinetic data obtained at the prespecified dose levels.
- measure
- Recommended Phase II Dose of Dasatinib in Children and Adolescents With Relapsed or Refractory Leukemia
- time Frame
- From the date of first dose to end-of-treatment (EOT) (Median duration of therapy in months: Stratum 1=24.11 [Range:2.27-50.63]; Stratum 2/3=3.02 [Range: 0.53-37.72]; Stratum 4=1.14 [Range: 0.03-3.38])
- secondary Outcomes
- description
- AE: New untoward medical occurrence or worsening of a preexisting medical condition that does not have causal relationship with this treatment. SAE: Untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, drug dependency/abuse; life-threatening, an important medical event, a congenital anomaly/birth defect; requires inpatient hospitalization/prolongs existing hospitalization. Grade 3 = Severe; Grade 4 = Life-threatening or disabling.
- measure
- 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.
- time Frame
- From the date of first dose until at least 30 days after the last dose of study drug (Median duration of therapy in months: Stratum 1=24.11 [Range: 2.27-50.63]; Stratum 2/3=3.02 [Range: 0.53-37.72]; Stratum 4=1.14 [Range: 0.03-3.38])
- description
- DLTs: AEs which were at least possibly drug-related occurring within first 3 weeks of dasatinib therapy (toxicities occurring after 21 days were also considered) and are:- --Any nonhematologic clinically-apparent toxicity of Grade(GR)≥3 occurring despite appropriate medical management and GR4 laboratory abnormality/GR3 lasting ≥7 days --GR4 neutropenia or thrombocytopenia lasting ≥7 days and not explained by the presence of leukemia after hematopoietic reconstitution --Any clinically important toxicity of GR≥2 requiring treatment discontinuation or interruption ≥7 days.
- measure
- Number of Participants With Dose-limiting Toxicity (DLT)
- time Frame
- From the date of first dose until at least 30 days after the last dose of study drug (Median duration of therapy in months: Stratum 1=24.11 [Range: 2.27-50.63]; Stratum 2/3=3.02 [Range: 0.53-37.72]; Stratum 4=1.14 [Range: 0.03-3.38])
- description
- GR1=Mild; GR2=Moderate; GR3=Severe; GR4=Life-threatening or disabling. Normal ranges provided by local laboratory and may also vary from site to site. WBC: GR1=\<LLN-3.0\*10\^9/L; GR2=\<3.0-2.0\*10\^9/L; GR3=\<2.0-1.0\*10\^9/L; GR4=\<1.0\*10\^9/L. ANC: GR1=\<LLN-1.5\*10\^9 /L; GR2=\<1.5-1.0\*10\^9/L; GR3=\<1.0-0.5\*10\^9/L; GR4=\<0.5\*10\^9/L. Hemoglobin: GR1=\<LLN-10.0g/dL; GR2=\<10.0-8.0g/dL; GR3=\<8.0-6.5g/dL; GR4=\<6.5g/dL. Platelets: GR1=\<LLN-75.0\*10\^9/L; GR2=\<75.0-50.0\*10\^9/L; GR3=\<50.0-25.0\*10\^9/L; GR4=\<25.0\*10\^9/L.
- measure
- Number of Participants With Hematology Abnormalities by NCI CTCAE Version 3.0
- time Frame
- Days 8, 15, 22, 29, 36, 43, then every 3 weeks, then every 3 months after 1 Year, EOT (Median duration of therapy in months: Stratum 1=24.11 [Range: 2.27-50.63]; Stratum 2/3=3.02 [Range: 0.53-37.72]; Stratum 4=1.14 [Range: 0.03-3.38])
- description
- GR1=Mild; GR2=Moderate; GR3=Severe; GR4=Life-threatening or disabling. Normal ranges provided by local laboratory and may also vary from site to site. Low calcium: GR1=\<LLN-8.0 mg/dL, GR2=\<8.0-7.0 mg/dL, GR3=\<7.0-6.0 mg/dL, GR4=\<6.0 mg/dL; Low magnesium: GR1=\<LLN-1.2 mg/dL, GR2=\<1.2-0.9 mg/dL, GR3=\<0.9-0.7 mg/dL, GR4=\<0.7 mg/dL; Low phosphate: GR1=\<LLN - 2.5 mg/dL, GR2=\<2.5 - 2.0 mg/dL, GR3=\<2.0 - 1.0 mg/dL, GR4=\<1.0 mg/dL.
- measure
- Number of Participants With Serum Chemistry Abnormalities (Calcium, Magnesium, and Phosphate) by NCI CTCAE Version 3.0
- time Frame
- Days 22 and 43, then every 12 weeks, then every 24 weeks after 24 months of treatment, EOT (Median duration of therapy in months: Stratum 1=24.11 [Range: 2.27-50.63]; Stratum 2/3=3.02 [Range: 0.53-37.72]; Stratum 4=1.14 [Range: 0.03-3.38])
- description
- GR1=Mild; GR2=Moderate; GR3=Severe; GR4=Life-threatening or disabling. Normal ranges provided by local laboratory and may also vary from site to site. AST and ALT: GR1=\>ULN-2.5\*ULN; GR2=\>2.5-5.0\*ULN; GR3=\>5.0-20.0\*ULN; GR4:\>20.0\*ULN. Total bilirubin:GR1=\>ULN-1.5\*ULN, GR2=\>1.5-3.0\*ULN, GR3=\>3-10\*ULN, GR4=\>10\*ULN. Creatinine: GR1=\>ULN-1.5\*ULN, GR2=\>1.5-3.0\*ULN, GR3=\>3.0-6.0\*ULN, GR4=\>6.0\*ULN.
- measure
- Number of Participants With Serum Chemistry Abnormalities (Liver and Renal Function) by NCI CTCAE Version 3.0
- time Frame
- Days 22 and 43, then every 12 weeks, then every 24 weeks after 24 months of treatment, EOT (Median duration of therapy in months: Stratum 1=24.11 [Range: 2.27-50.63]; Stratum 2/3=3.02 [Range: 0.53-37.72]; Stratum 4=1.14 [Range: 0.03-3.38])
- description
- Cytogenetic responses were based on the karyotype analysis of the percentage of Ph+ metaphases among cells in metaphase on a BM sample. At least 20 metaphase cells from a BM sample were evaluated. MCyR: A cytogenetic response that is either complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). CCyR: 0% Ph+ cells in metaphase in BM. PCyR: \>0% to 35% Ph+ cells in metaphase in BM.
- measure
- 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)
- time Frame
- Strata 1 and 2/3: At Week 7, 13, then every 12 weeks, and EOT; Stratum 2/3: Additionally at Week 4, 19, 31 (Median duration of therapy in months: Stratum 1=24.11 [Range: 2.27-50.63]; Stratum 2/3=3.02 [Range: 0.53-37.72])
- description
- Cytogenetic responses were based on the karyotype analysis of the percentage of Ph+ metaphases among cells in metaphase on a BM sample. At least 20 metaphase cells from a BM sample were evaluated. MCyR: A cytogenetic response that was either CCyR or PCyR. CCyR: 0% Ph+ cells in metaphase in BM. PCyR: \>0% to 35% Ph+ cells in metaphase in BM.
- measure
- Number of Participants With Major Cytogenetic Response (MCyR) in Stratum 1 (Ph+ CP-CML) Within First 12 and 24 Weeks
- time Frame
- After completion of Week 12 and 24 (measured at Weeks 13 and 25)
- description
- Best CyR was assessed based on the percentages of Ph+ metaphases of ≥20 analyzed metaphases in BM sample. Participants with complete, partial, minor, minimal, or no CyR. Refer to Outcome Measure 7 for definitions of CCyR and PCyR. Minor CyR:\>35%-65% Ph+ cells in metaphase in BM. Minimal CyR:\>65%-95% Ph+ cells in metaphase in BM. No CyR:\>95%-100% Ph+ cells in metaphase in BM. Unable to determine:Participants without valid cytogenetic assessment (i.e., at least 1 metaphase observed and number of Ph+ metaphases smaller than total number of metaphases \[%Ph+ \<100%\]).
- measure
- Best Cytogenetic Response (CyR) in Stratum 1 (Ph+ CP-CML) and Stratum 2/3 (Ph+ ALL or AP/BP-CML)
- time Frame
- Strata 1 and 2/3: At Weeks 7, 13, then every 12 weeks, and EOT; Stratum 2/3: Additionally at Weeks 4, 19, 25, 31 (Median duration of therapy in months: Stratum 1=24.11 [Range: 2.27-50.63]; Stratum 2/3=3.02 [Range: 0.53-37.72])
- description
- Cytogenetic responses were based on the karyotype analysis of the percentage of Ph+ metaphases among cells in metaphase on a BM sample. At least 20 metaphase cells from a BM sample were evaluated. MCyR: A cytogenetic response that was either CCyR or PCyR. CCyR: 0% Ph+ cells in metaphase in BM. PCyR: \>0% to 35% Ph+ cells in metaphase in BM.
- measure
- Percentage of Participants With Complete Cytogenetic Response (CCyR) or Major Cytogenetic Response (MCyR) at Recommended Phase II Dose
- time Frame
- Strata 1 and 2/3: At Week 7, 13, then every 12 weeks, and EOT; Stratum 2/3: Additionally at Week 4, 19, 31 (Median duration of therapy in months: Stratum 1=24.11 [Range: 2.27-50.63]; Stratum 2/3=3.02 [Range: 0.53-37.72])
- description
- Defined as time (in days) from the first dose of dasatinib until criteria were first met for MCyR. MCyR: A CyR that was either CCyR or PCyR. CCyR: 0% Ph+ cells in metaphase in BM. PCyR: \>0% to 35% Ph+ cells in metaphase in BM. The Kaplan-Meier plot was used. A 2-sided, 95% confidence interval (CI) for the median was computed using the Brookmeyer and Crowley method.
- measure
- Time to Major Cytogenetic Response (MCyR) in Responders: Stratum 1 (Ph+ CP-CML) and Stratum 2/3 (Ph+ ALL or AP/BP-CML)
- time Frame
- Strata 1 and 2/3: At Weeks 7, 13, 25, 37, then every 12 weeks; Stratum 2/3: Additionally at Weeks 4, 19, 31; until first MCyR (maximum participant time to first MCyR of 92 days).
- description
- Defined as the time (in months) from the first day that all criteria were met for MCyR until the date of progression (based on the Investigator's assessment) or death (for participants whose best responses were MCyR and CCyR respectively). MCyR: A cytogenetic response that was either CCyR or PCyR. CCyR: 0% Ph+ cells in metaphase in BM. PCyR: \>0% to 35% Ph+ cells in metaphase in BM. The Kaplan-Meier plot was used. A 2-sided, 95% CI for the median was computed using the Brookmeyer and Crowley method.
- measure
- Duration of Major Cytogenetic Response (MCyR) in Responders (Stratum 1 [Ph+ CP-CML] and Stratum 2/3 [Ph+ ALL or AP/BP-CML])
- time Frame
- From the date of first MCyR assessment to date of progression, death, or last tumor assessment (maximum participant duration of response of 48.6 months)
- description
- Defined as time (in months) from the first day that all criteria were met for CCyR until the date of progression (based on the Investigator's assessment) or death (for participants whose best response was CCyR). CCyR = 0% Ph+ metaphases of ≥ 20 analyzed metaphases in BM aspiration. The Kaplan-Meier plot was used. A 2-sided, 95% CI for the median was computed using the Brookmeyer and Crowley method.
- measure
- Duration of Complete Cytogenetic Response (CCyR) in Responders: Stratum 1 [Ph+ CP-CML] and Stratum 2/3 [Ph+ ALL or AP/BP-CML]
- time Frame
- From the date of first CCyR assessment to date of progression, death, or last tumor assessment (maximum participant duration of response of 45.1 months)
Full study description
- 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.
Source references
- references
- citation
- 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.
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Preserved source evidence · Not medical advice