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

Phase 1

Completed

Conditions: Chronic Myelogenous Leukemia
Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Interventions: Drug: dasatinib

Registration Number: NCT01030718

Lead Sponsor: Bristol-Myers Squibb

Brief Summary: 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)

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 54

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
dasatinib (CML-CP)	dasatinib	CML - Chronic Phase
dasatinib (Ph+ ALL)	dasatinib	Ph+ Acute Lymphoblastic Leukemia
dasatinib (CML-AP/BP)	dasatinib	CML - Accelerated Phase and Blast Phase

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuation	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	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

Name	Time	Method
Participants With CML-Accelerated or Blast Phase (AP/BP): Percentage of Participants With Cytogenetic Response	At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter	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	At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter	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)	At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454),	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 Chronic Phase CML (CML-CP): Percentage of Participants With Cytogenetic Response	At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454)	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-AP/BP and Ph+ ALL: Time to Complete Cytogenetic Response (CCyR)	At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter	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)	At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454)	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)	At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter	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)	At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454)	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)	At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter	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)	At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454)	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)	At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter	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)	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter, and at discontinuation	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)	At baseline and discontinuation--the study period was extended until the launch of dasatinib in Japan, January 2009.	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	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	Blood samples for pharmacokinetic analysis of Dasatinib BID that will contribute to population pharmacokinetic modeling were collected.