Rollover Study of BMS-354825 in Patients With CML and Ph+ALL

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01030718
First received: December 10, 2009
Last updated: November 15, 2010
Last verified: November 2010
  Purpose

To assess the safety of dasatinib (BMS-354825) in subjects with Imatinib resistant or intolerant chronic myelogenous leukemia (CML) and Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) who are resistant or intolerant to treatment and will continue study drug after completing the previous Phase I/II study (CA180031/NCT00337454)


Condition Intervention Phase
Chronic Myelogenous Leukemia
Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
Drug: dasatinib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study to Document the Long-Term Safety and Efficacy of BMS-354825 in Subjects With Imatinib Resistant or Intolerant Chronic Myelogenous Leukemia and Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Who Are Resistant or Intolerant to Previous Treatment and Have Completed the Previous Phase I/II Protocol (CA180-031/NCT00337454)

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuation [ Time Frame: baseline; every 4 weeks (if on study < 6 months, including CA180-031(NCT00337454); every 12 weeks (if on study >=6 months and <=2 years); every 24 weeks (if on study >2 years); at discontinuation ] [ Designated as safety issue: Yes ]
    AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.


Secondary Outcome Measures:
  • Participants With Chronic Phase CML (CML-CP): Percentage of Participants With Cytogenetic Response [ Time Frame: At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454) ] [ Designated as safety issue: No ]
    Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. The criteria for cytogenetic responses are as follows. Best CyR is defined as the best response obtained at any time during the study. Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Philadelphia positive [Ph+] Cells in Metaphase in BM).

  • Participants With CML-Accelerated or Blast Phase (AP/BP): Percentage of Participants With Cytogenetic Response [ Time Frame: At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter ] [ Designated as safety issue: No ]
    Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. The criteria for cytogenetic responses are as follows. Best CyR is defined as the best response obtained at any time during the study. Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM).

  • Participants With Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL): Percentage of Participants With Cytogenetic Response [ Time Frame: At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter ] [ Designated as safety issue: No ]
    Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. The criteria for cytogenetic responses are as follows. Best CyR is defined as the best response obtained at any time during the study. Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM).

  • Participants With CML-CP: Time to Complete Cytogenetic Response (CCyR) [ Time Frame: At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454), ] [ Designated as safety issue: No ]
    Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. Complete Cytogenetic Response (CCyR) = 0 Ph+ Cells in Metaphase in BM. Time to complete CCyR is defined as the time from first dose of dasatinib until measurement criteria are first met for CCyR, and is computed only for subjects whose best response is CCyR.

  • Participants With CML-AP/BP and Ph+ ALL: Time to Complete Cytogenetic Response (CCyR) [ Time Frame: At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter ] [ Designated as safety issue: No ]
    Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. Complete Cytogenetic Response (CCyR) = 0 Ph+ Cells in Metaphase in BM. Time to complete CCyR is defined as the time from first dose of dasatinib until measurement criteria are first met for CCyR, and is computed only for subjects whose best response is CCyR.

  • Participants With CML-CP: Duration of Complete Cytogenetic Response (CCyR) [ Time Frame: At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454) ] [ Designated as safety issue: No ]
    Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. Complete Cytogenetic Response (CCyR) = 0 Ph+ Cells in Metaphase in BM. Duration of CCyR was measured from the time measurement criteria are first met for CCyR until the first date of progressed disease (PD) or death. Subjects who neither relapsed nor died will be censored on the date of their last assessment.

  • Participants With CML-AP/BP and Ph+ALL: Duration of Complete Cytogenetic Response (CCyR) [ Time Frame: At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter ] [ Designated as safety issue: No ]
    Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. Complete Cytogenetic Response (CCyR) = 0 Ph+ Cells in Metaphase in BM. Duration of CCyR was measured from the time measurement criteria are first met for CCyR until the first date of PD or death. Subjects who neither relapsed nor died will be censored on the date of their last assessment.

  • Participants With CML-CP: Time to Major Cytogenetic Response (MCyR) [ Time Frame: At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454) ] [ Designated as safety issue: No ]
    Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM). Time to MCyR was defined as the time from first dose of dasatinib until measurement criteria were first met for CCyR or PCyR (whichever status is recorded first).

  • Participants With CML-AP/BP and Ph+ALL: Time to Major Cytogenetic Response (MCyR) [ Time Frame: At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter ] [ Designated as safety issue: No ]
    Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM). Time to MCyR was defined as the time from first dose of dasatinib until measurement criteria were first met for CCyR or PCyR (whichever status is recorded first).

  • Participants With CML-CP: Duration of Major Cytogenetic Response (MCyR) [ Time Frame: At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454) ] [ Designated as safety issue: No ]
    Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM). Duration of MCyR was measured from the time measurement criteria are first met for CCyR or PCyR (whichever status is recorded first) until the first date of progressive disease (PD) or death. Subjects who neither relapsed nor died were censored on the date of their last assessment.

  • Participants With CML-AP/BP and Ph+ ALL: Duration of Major Cytogenetic Response (MCyR) [ Time Frame: At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter ] [ Designated as safety issue: No ]
    Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM). Duration of MCyR was measured from the time measurement criteria are first met for CCyR or PCyR (whichever status is recorded first) until the first date of progressive disease (PD) or death. Subjects who neither relapsed nor died were censored on the date of their last assessment.

  • Participants With CML-CP: Percentage of Participants With Complete Hematologic Response (CHR) [ Time Frame: baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454), every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation ] [ Designated as safety issue: No ]
    CHR=all of the following criteria: white blood cell count (WBC) ≤institutional upper limit of normal(ULN); platelets <450,000/mm³; no blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils <20%; no extramedullary involvement.

  • Participants With CML-AP/BP: Percentage of Participants With Hematologic Response [ Time Frame: baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation ] [ Designated as safety issue: No ]
    Major Hematologic Response=Complete Hematologic Response (CHR) or No Evidence of Leukemia (NEL). CHR=WBC <ULN; absolute neutrophil count (ANC) >1,000/mm3; platelets >100,000/mm3; no blasts or promyelocytes in peripheral blood; BM blasts ≤5%; <5% myelocytes + metamyelocytes in peripheral blood; <20% basophils in peripheral blood; no extramedullary involvement. NEL=(see Outcome Measure 15, below). Overall hematologic response (OHR)=best response of CHR, NEL or return to chronic phase (RTC).

  • Participants With Ph+ ALL: Percentage of Participants With Hematologic Response [ Time Frame: baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation ] [ Designated as safety issue: No ]
    Major Hematologic Response=Complete Hematologic Response (CHR) or No Evidence of Leukemia (NEL). CHR=(see Outcome Measure 14, above). NEL=WBC ≤ULN; BM blasts ≤5%; no blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; <20% peripheral blood basophils; no extramedullary involvement; and at least 1 of the following: ANC ≥500/mm3 and <2000/mm3 or platelets ≥20,000/mm3 and <100,000/mm3. Overall hematologic response (OHR)=best response of CHR, NEL or return to chronic phase (RTC).

  • Time to Complete Hematologic Response (CHR) in Chronic Phase CML, Accelerated or Blast Phase CML, and Ph+ALL [ Time Frame: baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation ] [ Designated as safety issue: No ]
    CHR=all of the following criteria: WBC ≤institutional upper limit of normal(ULN); platelets <450,000/mm³; no blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils <20%; no extramedullary involvement. Time to CHR=time from first dose of dasatinib until the first day criteria for CHR are met provided they are confirmed 28 days later and was computed only for chronic phase CML subjects whose best response is CHR. Subjects who neither progressed nor died were censored at date of last hematologic assessment.

  • Duration of Complete Hematologic Response (CHR) in Chronic Phase CML, Accelerated or Blast Phase CML, and Ph+ALL [ Time Frame: baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation ] [ Designated as safety issue: No ]
    Duration of CHR was computed only for chronic phase CML subjects whose best response is CHR. It was measured from the first day complete hematologic response criteria are met provided they are confirmed 28 days later until the date treatment is discontinued due to PD or death. Subjects who neither progressed nor died were censored on the date of their last hematologic assessment.

  • Time to Major Hematologic Response (MaHR) in Accelerated or Blast Phase CML, and Ph+ALL [ Time Frame: baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation ] [ Designated as safety issue: No ]
    Major Hematologic Response=Complete Hematologic Response (CHR) or No Evidence of Leukemia (NEL; see Outcome Measures 14 and 15 for full definitions). Time to major hematologic response (MaHR)=time from first dose of dasatinib until the first day the measurement criteria for MaHR and is computed only for advanced diseases subjects whose best response is a major hematologic response. Subjects who neither progressed nor died were censored on the date of their last hematologic assessment.

  • Duration of Major Hematologic Response (MaHR) in Accelerated or Blast Phase CML, and Ph+ALL [ Time Frame: baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation ] [ Designated as safety issue: No ]
    Major Hematologic Response (MaHR)=Complete Hematologic Response (CHR) or No Evidence of Leukemia (NEL; see Outcome Measures 14 and 15 for full definitions). Subjects who neither progressed nor died were censored on the date of their last hematologic assessment.

  • Time to Overall Hematologic Response (OHR) in Accelerated or Blast Phase CML, and Ph+ALL [ Time Frame: baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation ] [ Designated as safety issue: No ]
    The overall hematologic response (OHR) rate is defined as the proportion of all treated subjects with a best response of major or minor hematologic response. Time to OHR = time from first dose of dasatinib until the first day measurement criteria are first met for hematologic response provided they were confirmed 28 days later. Subjects who neither progressed nor died were censored on the date of last hematologic assessment.

  • Duration of Overall Hematologic Response (OHR) in Accelerated or Blast Phase CML, and Ph+ALL [ Time Frame: baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation ] [ Designated as safety issue: No ]
    The overall hematologic response (OHR) rate is defined as the proportion of all treated subjects with a best response of major or minor hematologic response. Subjects who neither progressed nor died were censored on the date of last hematologic assessment.

  • Participants With Detectable Mutations of RNA (mRNA) of BCR-ABL at Baseline and at Best Achievement [ Time Frame: At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter, and at discontinuation ] [ Designated as safety issue: No ]
    Detectable BCR-ABL transcripts (b3a2, b2a2 or minor) >=2.0 log copy/micrograms RNA, as measured by real-time quantitative PCR (RQ-PCR) at baseline and best achievement post-dose.

  • Status of Point Mutations of BCR-ABL at Baseline (BL) and End of Study (EOS) [ Time Frame: At baseline and discontinuation--the study period was extended until the launch of dasatinib in Japan, January 2009. ] [ Designated as safety issue: No ]
    Point mutations of BCR-ABL detected or undetected in the Quantitative real-time PCR polymerase chain reaction (RQ-PCR) products

  • Collection of Blood Samples for Pharmacokinetic Analysis of Dasatinib Twice Daily (BID) That Will Contribute to Population Pharmacokinetic Modeling [ Time Frame: At any visit of later than Day 7, draw sample(s) at pretreatment trough (within 1 hour prior to dosing) or between 3 hours following treatment and prior to the next dose ] [ Designated as safety issue: No ]
    Blood samples for pharmacokinetic analysis of Dasatinib BID that will contribute to population pharmacokinetic modeling were collected.


Enrollment: 54
Study Start Date: January 2006
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: dasatinib (CML-CP)
CML - Chronic Phase
Drug: dasatinib
Tablet, Oral, (50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID
Other Names:
  • Sprycel
  • BMS-354825
Experimental: dasatinib (CML-AP/BP)
CML - Accelerated Phase and Blast Phase
Drug: dasatinib
Tablet, Oral, (50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID
Other Names:
  • Sprycel
  • BMS-354825
Experimental: dasatinib (Ph+ ALL)
Ph+ Acute Lymphoblastic Leukemia
Drug: dasatinib
Tablet, Oral, (50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID
Other Names:
  • Sprycel
  • BMS-354825

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects who were eligible and completed the previous Phase I and II study (CA180031/NCT00337454) and for whom the principal investigator has deemed that continuation of study drug is in the best interest of the subject

Exclusion Criteria:

  • Women who are pregnant or breastfeeding
  • Subjects who are eligible and willing to undergo transplantation at pre-study
  • Non-hematologic intolerance to Dasatinib (BMS-354825) in the previous Phase I and II study (CA180031/NCT00337454)
  Contacts and Locations
No Contacts or Locations Provided
  More Information

Additional Information:
No publications provided

Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01030718     History of Changes
Other Study ID Numbers: CA180-036
Study First Received: December 10, 2009
Results First Received: July 26, 2010
Last Updated: November 15, 2010
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Philadelphia Chromosome
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes
Dasatinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014