A Phase II Study of Dasatinib in Children and Adolescents With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia (CML) or With Ph+ Leukemias Resistant or Intolerant to Imatinib

Bristol-Myers Squibb (BMS)

Status and phase: Active, not recruiting; Phase 2

Conditions: Leukemia

Treatments: Drug: Dasatinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT00777036

CA180-226

2008-002260-33 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to determine whether dasatinib is safe and effective in children and adolescents with newly diagnosed chronic myeloid leukemia (CML), or in children with Ph+ acute lymphoblastic leukemia (ALL), accelerated or blast phases CML who relapse after imatinib or who are resistant or intolerant to imatinib. The side effects of this oral investigational drug in children and adolescents will be evaluated

Enrollment: 130 patients

Sex: All

Ages: 1 day to 18 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Inclusion Criteria:

• CP-CML who prove resistant or intolerant to imatinib (Cohort 1)
• Ph+ ALL, AP-CML, or BP-CML who are resistant or intolerant to or who relapse after imatinib therapy (Cohort 2)
• Newly diagnosed, treatment naive CP-CML (Cohort 3)
• Lansky or Karnofsky scale >50
• Life expectancy ≥12 weeks
• Adequate hepatic and renal function
• Written informed consent
• Target Population for the PK substudy must obtain written informed consent from subject, or from parents or legal guardians for minor subjects, according to local law and regulation
• Target Population for the PK substudy subjects must have CP-CML and be taking daily dasatinib (tablets or PFOS) either as part of Cohort 1 or Cohort 3 of this protocol. Patients receiving commercial dasatinib tablets outside of this protocol may be invited to participate in this PK substudy
• Target Population for the PK substudy subjects with CP-CML who are tolerating dasatinib tablet dose of at least 60 mg/m2 or dasatinib PFOS dose of at least 72 mg/m2
• Target Population for the PK substudy prior exposure to imatinib or other TKI therapy is permissible
• Target Population for the PK substudy subjects must meet relevant inclusion criteria

Exclusion Criteria:

• Eligibility for potentially-curative therapy including hematopoietic stem-cell transplantation
• Symptomatic CNS involvement (other than signs and symptoms caused by leptomeningeal disease)
• Isolated extramedullary disease
• Prior therapy with Dasatinib
• Target Population for the PK substudy subjects participating in the PK substudy must comply with the relevant exclusion criteria
• Target Population for the PK substudy subjects are not allowed to use proton pump inhibitors, H2 antagonists, CYP3A4 inhibitors and inducers when entering the PK substudy

Other inclusion/exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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130 participants in 3 patient groups

Cohort 1: Imatinib-resistant/intolerant CP-CML

Experimental group

Description:

Dasatinib 60 mg/m² tablet every day (QD) [with a maximum dose of 100 mg QD for subjects with high BSA] for minimum of 24 months, may continue as long as deriving clinical benefit OR Dasatinib 72 mg/m² powder for oral suspension (PFOS) QD [with a maximum dose of 120 mg QD for subjects with high BSA] for minimum of 24 months, may continue as long as deriving clinical benefit

Treatment:

Drug: Dasatinib

Cohort 2: Ph+ALL or AP- or BP-CML

Experimental group

Description:

Dasatinib 80 mg/m² tablet QD [with a maximum dose of 140 mg QD for subjects with high BSA] for minimum of 24 months, may continue as long as deriving clinical benefit OR Dasatinib 96 mg/m² PFOS QD [with a maximum dose of 170 mg QD for subjects with high BSA] for minimum of 24 months, may continue as long as deriving clinical benefit

Treatment:

Drug: Dasatinib

Cohort 3: Newly diagnosed, treatment naïve CP-CML

Experimental group

Description:

Dasatinib 60 mg/m² tablet QD [with a maximum dose of 100 mg QD for subjects with high BSA] for minimum of 24 months, may continue as long as deriving clinical benefit OR Dasatinib 72 mg/m² PFOS QD [with a maximum dose of 120 mg QD for subjects with high BSA] for minimum of 24 months, may continue as long as deriving clinical benefit

Treatment:

Drug: Dasatinib