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

NCT00306202 | Completed Phase 1 Results

• 3 other identifiers: CA180-018Protocol ITCC 0052005-002882-35
• Study Type: interventional
• Target: 63
• Locations: 6 countries
• Sites: 13

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

Keywords

Relapsed and Refractory Leukemia

Outcome Measures

Primary Outcomes (1)

• Recommended Phase II Dose of Dasatinib in Children and Adolescents With Relapsed or Refractory Leukemia

  The recommended phase 2 dasatinib dose was determined based on efficacy, safety, and pharmacokinetic data obtained at the prespecified dose levels.

  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 (45)

• 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.

  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])

• Number of Participants With Dose-limiting Toxicity (DLT)

  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])

• Number of Participants With Hematology Abnormalities by NCI CTCAE Version 3.0

  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])

• Number of Participants With Serum Chemistry Abnormalities (Calcium, Magnesium, and Phosphate) by NCI CTCAE Version 3.0

  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])

• Number of Participants With Serum Chemistry Abnormalities (Liver and Renal Function) by NCI CTCAE Version 3.0

  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])

Other Outcomes (3)

• Number of Participants With Hematologic Toxicity at Baseline by NCI CTCAE Version 3.0

  At baseline (within 1 week before initiation of study therapy)

• Number of Participants With Serum Chemistry Abnormalities (Liver and Renal Function) at Baseline by NCI CTCAE Version 3.0

  At baseline (within 1 week before initiation of study therapy)

• Number of Participants With Serum Chemistry Abnormalities (Calcium, Magnesium, and Phosphate) at Baseline by NCI CTCAE Version 3.0

  At baseline (within 1 week before initiation of study therapy)

Study Arms (3)

Stratum 1 (Ph+ CP-CML)

EXPERIMENTAL

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

Drug: Dasatinib

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

EXPERIMENTAL

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)

Drug: Dasatinib

Stratum 4 (Ph- ALL/AML)

EXPERIMENTAL

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

Drug: Dasatinib

Interventions

Dasatinib 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).

Also known as: Sprycel, BMS-354825

Stratum 1 (Ph+ CP-CML)

Eligibility Criteria

• Age: 12 Months - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Innovative Therapies For Children with Cancer Consortium: collaborator

Study Sites (13)

Local Institution

Vienna, 1090, Austria

Location

Local Institution

Nantes, 44093, France

Location

Local Institution

Paris, 75475, France

Location

Local Institution

Paris, 75571, France

Location

Local Institution

Berlin, 13353, Germany

Location

Local Institution

Frankfurt, 60590, Germany

Location

Local Institution

Hanover, 30625, Germany

Location

Local Institution

Monza (mi), 20052, Italy

Location

Local Institution

Rotterdam, 3015 GJ, Netherlands

Location

Local Institution

Manchester, Greater Manchester, M27 4HA, United Kingdom

Location

Local Institution

Bristol, Somerset, BS2 8BJ, United Kingdom

Location

Local Institution

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Local Institution

Birmingham, West Midlands, B4 6NH, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 23715577 DERIVED

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

MeSH Terms

Conditions

Leukemia; Recurrence

Interventions

Dasatinib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Results Point of Contact

• Title: BMS Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2006
• First Posted: March 23, 2006
• Study Start: March 31, 2006
• Primary Completion: May 31, 2011
• Study Completion: May 22, 2019
• Last Updated: February 26, 2021
• Results First Posted: July 23, 2012

Record last verified: 2021-02

Locations

AU (1); FR (3); NL (1); GB (4); IT (1); DE (3)