Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Philadelphia Chromosome

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Translocation, Genetic

Chromosome Aberrations

Myeloid Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Dasatinib

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Tablets, oral, 20 mg and 50mg, twice daily, up to 96 weeks

Tablets, Oral, 400mg and 100mg, twice daily, up to 96 weeks

Imatinib

Bristol-Myers Squibb

The primary purpose of this study is to estimate the major cytogenetic response rates of BMS-354825 and imatinib (800 mg/d) in subjects with chronic phase, Philadelphia chromosome positive, chronic myeloid leukemia (PH+ CML) with disease resistant to imatinib at a dose of 400-600 mg/d.

Dasatinib (BMS-354835) Versus Imatinib Mesylate in Subjects With Chronic Myeloid Leukemia

A Randomized Multi-Center Open Label Study of BMS-354825 vs. Imatinib Mesylate (Gleevec) 800 mg/d in Subjects With Chronic Phase Philadelphia Chromosome-Positive Chronic Myeloid Leukemia Who Have Disease That is Resistant to Imatinib at a Dose at 400 - 600 mg/d

Cytogenetic response was based on the prevalence of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a bone marrow sample (aspirate/biopsy). MCyR was defined as Complete CyR (CCyR; 0% Ph+ cells in metaphase in bone marrow) or Partial CyR (PCyR; \>0% to 35% Ph+ cells in metaphase in bone marrow).

Cytogenetic response was based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow sample (aspirate/biopsy). MCyR was defined as CCyR (0% Ph+ cells in metaphase in bone marrow) or PCyR (\>0% to 35% Ph+ cells in metaphase in bone marrow).

Percentage of participants who achieved MCyR and did not progress at 12 and 18 months.

Percentage of participants who achieved MCyR and did not progress at 24 months.

Median time from first dosing date to date of MCyR

Participants achieving CHR prior to crossover. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; 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. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response.

Percentage of participants who achieved CHR and did not progress at specified time points. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; 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. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response.

Median time from first dosing date to date of CHR. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; 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. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response.

Number of participants Achieving MMR. MMR is defined as ≤3 log reduction (ie, international ratio ≤0.1), in BCR-ABL levels from the standardized baseline value of BCR-ABL: Control Gene ratio. The international ratio is obtained by multiplying BCR-ABL: Control gene ratio by the lab-specific conversion factor.

Participants achieving CHR after crossover. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; 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. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response.

Cytogenetic response was based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow sample (aspirate/biopsy). MCyR was defined as Complete CyR (0% Ph+ cells in metaphase in bone marrow) or Partial CyR (\>0% to 35% Ph+ cells in metaphase in bone marrow).

AE=any new untoward medical occurrence or worsening of a pre-existing medical condition regardless of causal relationship with treatment. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death)

Health-related quality of life as measured by Functional Assessment of Cancer Therapy-General (FACT-G). FACT-G=27 questions in 4 domains: physical, social/family, emotional, \& functional well-being (PWB, SWB, EWB, FWB). Higher scores=better health-related quality of life. Total Score change of 7 or more=minimal clinical important change; PWB, EWB, \& FWB score change of 3 or more, \& SWB score change of 2 or more=minimal clinical important change.

Number of participants from which blood samples were collected for population PK studies.

Study Director

DASATINIB

IMATINIB

Total

Between 21 and 45 years

Between 46 and 65 years

Between 66 and 75 years

>75 years

Age, Customized

Age Continuous

Sex: Female, Male

Asian

Black or African American

White

Other

Race/Ethnicity, Customized

Score=0 (fully active)

Score=1 (ambulatory, light/sedentary work)

Score=2 (ambulatory, all selfcare, unable to work)

Score=3 (limited selfcare, some bed confinement)

Score=4 (completely disabled)

Score=5 (dead)

Not Reported

ECOG PS: a 6-item scale to assess disease progression, daily functioning, and appropriate treatment and prognosis. Scale: 0-5, with 0=fully active, able to carry on all pre-disease performance without restriction and 5=death.

Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS)

BMS Study Director

Number of Participants With Major Cytogenetic Response (MCyR) at Week 12

MCyR (CCyR + PCyR)

CCyR (0% Ph+ cells)

PCyR (>0% to 35% Ph+ cells)

MCyR at Any Time Prior to Crossover

12 months

18 months

Duration of MCyR at 12 Months and 18 Months

In the imatinib group, the 24 months timepoint was beyond the maximum observed time.

Duration of MCyR at 24 Months

Population consists of the number of responders in each treatment group

Time to MCyR Prior to Crossover

Complete Hematologic Response (CHR) at Any Time Prior to Crossover

24 months

Number of participants achieving CHR in each treatment group

Duration of Complete Hematologic Response (CHR)

Time to CHR Prior to Crossover

Major Molecular Response (MMR)

Participants evaluable for response after crossover

CHR After Crossover

Major Cytogenetic Response (MCyR)

Complete Cytogenetic Response (CCyR)

Partial Cytogenetic Response (PCyR)

Participants evaluable for after crossover response

Cytogenetic Response After Crossover

Any Adverse Event (AE)

Grade 3-4 AEs

Drug-related AEs

Drug-related Grade 3-4 AEs

Death within 30 days of last dose

Drug-related Serious AEs

AEs leading to discontinuation

Fluid Retention AEs - Overall

Fluid Retention AEs - Superficial Edema

Fluid Retention AEs - Pleural Effusion

Fluid Retention AEs - Other

Grade 3-4 Hematologic Toxicity - Anemia

Grade 3-4 Hematologic Toxicity - Thrombocytopenia

Grade 3-4 Hematologic Toxicity - Neutropenia

Grade 3-4 Hematologic Toxicity - Leukopenia

Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover

Since single-arm quality-of-life data are not interpretable in a non-comparative trial, these data were not analyzed.

Health-Related Quality of Life Prior to Crossover

Blood samples that were to contribute to PK modeling were collected from 78 participants,to be included in separate population PK analyses. Although blood sample collection was listed as a secondary endpoint, no study-specific PK analyses were planned for this report.

Blood Sample Collection for Pharmacokinetic (PK) Analysis of Dasatinib

Dasatinib 70 mg twice a day (BID) in the first intervention period and, if intolerance to dasatinib or progression, imatinib 400 mg BID in the second intervention period (after washout period).

Dasatinib First

Imatinib 400 mg BID in the first intervention period and, if intolerance to imatinib or progression or lack of efficacy, dasatinib 70 mg BID in the second intervention period (after washout period).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Dasatinib (BMS-354835) Versus Imatinib Mesylate in Subjects With Chronic Myeloid Leukemia	NCT00103844	Chronic Myeloid... Philadelphia-Po...	Dasatinib Imatinib	18 Years -	Bristol-Myers Squibb
Dasatinib (BMS-354835) Versus Imatinib Mesylate in Subjects With Chronic Myeloid Leukemia	NCT00103844	Chronic Myeloid... Philadelphia-Po...	Dasatinib Imatinib	18 Years -	Bristol-Myers Squibb

Spots Global Cancer Trial Database for chronic phase philadelphia chromosome positive (ph+) chronic myeloid leukemia