We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00777036
Recruitment Status : Active, not recruiting
First Posted : October 22, 2008
Results First Posted : January 5, 2018
Last Update Posted : January 5, 2018
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
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

Condition or disease Intervention/treatment Phase
Leukemia Drug: Dasatinib Phase 2

Detailed Description:
Cohort 2 was closed early to enrollment based on insufficient treatment response and poor enrollment

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 145 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Dasatinib in Children and Adolescents With Newly Diagnosed Chronic Phase CML or With Ph+ Leukemias Resistant or Intolerant to Imatinib
Actual Study Start Date : February 19, 2009
Primary Completion Date : September 1, 2016
Estimated Study Completion Date : September 23, 2021


Arms and Interventions

Arm Intervention/treatment
Experimental: Cohort 1: Imatinib-resistant/intolerant CP-CML

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 (PFSO) 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

Drug: Dasatinib
Other Name: Sprycel (BMS-354825)
Experimental: Cohort 2: Ph+ALL or AP- or BP-CML

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 PFSO 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

Drug: Dasatinib
Other Name: Sprycel (BMS-354825)
Experimental: Cohort 3: Newly diagnosed, treatment naïve CP-CML

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 PFSO 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

Drug: Dasatinib
Other Name: Sprycel (BMS-354825)


Outcome Measures

Primary Outcome Measures :
  1. Major Cytogenetic Response (MCyR) Rate [ Time Frame: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months) ]
    Major Cytogenetic Response (MCyR) rate is defined as the proportion of all treated participants who achieved a complete (0%) or partial (1%-35% Ph+ metaphases in at least 20 metaphases in bone marrow) cytogenetic response, expressed as percentage. The denominator of the MCyR response rate consists of all treated participants in Cohort 1, and the numerator is all participants in Cohort 1 achieving MCyR. 95% confidence interval was calculated by Clopper-Pearson exact method.

  2. Complete Hematologic Response (CHR) Rate [ Time Frame: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months) ]
    Complete Hematologic Response (CHR) rate is defined as the proportion of all treated participants who achieve a confirmed CHR while on-study, expressed as percentage. CHR is defined as including no more than 5% blasts in bone marrow and normal white blood cell count without blasts in peripheral blood, expressed as percentage. The denominator of the CHR response rate consists of all treated participants in Cohort 2, and the numerator is all participants in Cohort 2 achieving CHR. 95% confidence interval was calculated by Clopper-Pearson exact method.

  3. Complete Cytogenetic Response (CCyR) Rate [ Time Frame: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months) ]
    Complete Cytogenetic Response (CCyR) rate is defined as the proportion of all treated participants who achieve a CCyR while on-study, expressed as a percentage. CCyR rate is defined as 0% Ph+ metaphases in at least 20 metaphases in bone marrow. The denominator of the CCyR response rate consists of all treated participants in Cohort 3, and the numerator is all participants in Cohort 3 achieving CCyR. 95% confidence interval was calculated by Clopper-Pearson exact method.


Secondary Outcome Measures :
  1. Major Cytogenetic Response (MCyR) Rate in Cohort 2 [ Time Frame: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months) ]
    Major Cytogenetic Response (MCyR) rate was defined as the proportion of all treated participants who achieved a complete (0%) or partial (1%-35% Ph+ metaphases in at least 20 metaphases in bone marrow) cytogenetic response. The percentage of treated participants in each arm with MCyR is reported.

  2. Complete Hematologic Response (CHR) Rate in Cohorts 1 and 3 [ Time Frame: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months) ]
    Complete Hematologic Response (CHR) rate defined as the proportion of all treated participants who achieve a confirmed CHR while on-study. CHR is defined as including no more than 5% blasts in bone marrow and normal white blood cell count without blasts in peripheral blood. The percentage of treated participants in each arm with CHR is reported.

  3. Rate of Best Cytogenetic Response [ Time Frame: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months) ]
    The number of participants achieving their best on-study cytogenetic response was reported as a percentage of all treated participants in that arm.

  4. Time to Major Cytogenetic Response (MCyR) [ Time Frame: From first dose until MCyR criteria are met (assessed up to September 2016, approximately 90 months) ]
    Time to MCyR is defined as the time from first dose of dasatinib until the first day MCyR criteria are met, computed only for participants whose best response is MCyR.

  5. Duration of Major Cytogenetic Response (MCyR) [ Time Frame: From first day criteria are met for MCyR until the date PD is reported or death (assessed up to September 2016, approximately 90 months) ]
    Duration of MCyR will be computed from the first day criteria are met for MCyR until the date PD is reported (or treatment is discontinued for PD) or death. Participants who neither discontinue due to PD nor die will be censored on the date of their last hematologic or cytogenetic assessment, whichever comes last.

  6. Time to Complete Cytogenetic Response (CCyR) [ Time Frame: From first dose until CCyR criteria are met, assessed up to September 2016 (approximately 90 months) ]
    Time to CCyR is defined as the time from first dose of dasatinib until the first day CCyR criteria are met, computed only for participants whose best response is CCyR.

  7. Duration of Complete Cytogenetic Response (CCyR) [ Time Frame: From first day criteria are met for CCyR until the date of progressive disease or death (assessed up to September 2016, approximately 90 months) ]
    Duration of CCyR will be computed from the first day criteria are met for CCyR until the date PD is reported (or treatment is discontinued for PD) or death. Participants who neither discontinue due to PD nor die will be censored on the date of their last hematologic or cytogenetic assessment, whichever comes last.

  8. Progression-Free Survival (PFS) Rate at 2 Years [ Time Frame: 2 years ]
    PFS is defined as time from the first dosing date until the time PD is first documented by the investigator or death. Participants who die without a reported date of progression will be considered to have progressed on the date of death. Participants who neither progress nor die will be censored on the date of their last cytogenetic or hematologic assessment. The percentages of progression-free participants at 2 years are based on Kaplan-Meier estimation.

  9. Time to Complete Hematologic Response (CHR) [ Time Frame: From first dose until CHR criteria are met, assessed up to September 2016 (approximately 90 months) ]
    Time to CHR is defined as the time from first dose of dasatinib until the first day CHR criteria are met, provided they are confirmed 4 weeks later, computed only for participants whose best response is CHR.

  10. Duration of Complete Hematologic Response (CHR) [ Time Frame: From first day criteria are met for CHR until date of disease progression or death (assessed up to September 2016, approximately 90 months) ]
    Duration of CHR will be computed from the first day all criteria are met for CHR, provided they are confirmed 4 weeks later, until the date progressive disease (PD) is reported (or treatment is discontinued for PD) or death. Participants who neither discontinue due to PD nor die will be censored on the date of their last hematologic assessment.

  11. Disease-Free Survival Rate at 2 Years [ Time Frame: 2 years ]
    Disease free survival is defined as time from CCyR for participants with newly diagnosed chronic phase CML and for participants with chronic phase CML who are resistant or intolerant to imatinib (cohort 3 and cohort 1), and as time from CHR for participants with advanced phase CML and PH + ALL (cohort 2) until the time progression is first documented by the investigator or death from any cause. The percentages of disease-free participants at 2 years are based on Kaplan-Meier estimation.

  12. Overall Survival (OS) Rate at 2 Years [ Time Frame: 2 years ]
    OS is defined as time from the first dosing date until the time of death. All participants will be followed yearly for survival for up to 5 years after treatment discontinuation. Participants who have not died or who are lost to follow-up will be censored on the last date the participant is known to be alive. The percentages of surviving participants at 2 years are based on Kaplan-Meier estimation.

  13. Major Molecular Response (MMR) Rate [ Time Frame: From date of first treatment to date of MMR (assessed up to September 2016, approximately 90 months) ]
    Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (qPCR). MMR for participants with the p210 BCR-ABL transcript variant was defined as a ratio BCR-ABL/ABL <= 10-3 or 0.1% on the international scale. In this study, ABL was used as the control-gene. For a participant with the p190 BCR-ABL transcript variant (occurring in Cohort 2 only), on-study assessments were compared to the participant's individual baseline BCR-ABL/ABL ratio and a reduction to < 0.1% or a 3-log reduction from baseline was considered an MMR.

  14. Complete Molecular Response (CMR) Rate [ Time Frame: From date of first treatment to date of CMR (assessed up to September 2016, approximately 90 months) ]
    Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (qPCR). (CMR) is defined as absence of BCR-ABL rearrangements by real-time qPCR analysis. The percentage of treated participants with CMR is reported by arm.

  15. Major Cytogenetic Response (MCyR) Rate up to 2 Years [ Time Frame: 24 months ]
    Major Cytogenetic Response (MCyR) rate is defined as the proportion of all treated participants who achieved a complete (0%) or partial (1%-35% Ph+ metaphases in at least 20 metaphases in bone marrow) cytogenetic response. The percentage of treated participants with MCyR is reported by arm.

  16. Complete Cytogenetic Response (CCyR) Rate up to 2 Years [ Time Frame: 24 months ]
    Complete Cytogenetic Response (CCyR) rate is defined as the proportion of all treated participants who achieve a CCyR while on-study. CCyR rate is defined as 0% Ph+ metaphases in at least 20 metaphases in bone marrow. The percentage of treated participants with CCyR is reported by arm.

  17. Major Molecular Response (MMR) Rate up to 2 Years [ Time Frame: 24 months ]
    Molecular response will be assessed using BCR-ABL transcript levels measurement by real-time qPCR. MMR for participants with the p210 BCR-ABL transcript variant is defined according to the recommendations of Hughes et al. as a ratio BCR-ABL/ABL <= 10-3 or 0.1% on the international scale proposed by the authors. The standardized baseline, as established in the IRIS trial, is taken to represent 100% on the international scale and a 3-log reduction in ratio (BCR-ABL transcripts/ABL or BCR) from the standardized baseline (MMR) is fixed at 0.1%. In this study, ABL or other housekeeping gene, will be used as the control-gene. For a participant with the p190 BCR-ABL transcript variant, on-study assessments will be compared to the participant's individual baseline BCR-ABL/ABL ratio and a reduction to < 0.1% or a 3-log reduction from baseline will be considered an MMR. The percentage of treated participants with MMR is reported by arm.

  18. Complete Molecular Response (CMR) Rate up to 2 Years [ Time Frame: 24 months ]
    Molecular response will be assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (qPCR). (CMR) is defined as absence of BCR-ABL rearrangements by real-time qPCR analysis. The percentage of treated participants with CMR is reported by arm.


Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00777036


  Show 82 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
More Information

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00777036     History of Changes
Other Study ID Numbers: CA180-226
2008-002260-33 ( EudraCT Number )
First Posted: October 22, 2008    Key Record Dates
Results First Posted: January 5, 2018
Last Update Posted: January 5, 2018
Last Verified: December 2017

Keywords provided by Bristol-Myers Squibb:
Leukemia, Pediatric

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Chronic-Phase
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Imatinib Mesylate
Dasatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action