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LeukemiaPhase 1NCT00978731

Chronic Myelogenous Leukemia or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemic Study

A Phase 1 study testing Dasatinib in people with Leukemia, run by Bristol-Myers Squibb.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

To determine the long term safety and tolerability of dasatinib exposure in subjects previously treated in CA180-002. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia
What is being tested?
Dasatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
No sites listed yet
Study dates
Dec 2005to Sep 2008
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed written informed consent
  • Previous treatment with dasatinib on protocol CA180-002 and receiving clinical benefit in the opinion of the investigator
  • Completed a minimum of 3 months on protocol CA180-002
  • Eastern Cooperative Oncology Group (ECOG)performance status 0, 1, or 2 (See Appendix 1)
  • Prior history of Ph+ chronic, accelerated, or blast phase CML or Ph+ ALL

Who cannot join

  • Women of childbearing potential(WOCBP)who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 12 weeks after the study
  • WOCBP using a prohibited contraceptive method
  • Women who are pregnant or breastfeeding
  • Met the criteria as defined in protocol CA180-002 for discontinuation of therapy which includes:
  • Withdrawal of informed consent (subject's decision to withdraw for any reason)
  • Any clinical adverse event, laboratory abnormality or intercurrent illness which, in the opinion of the investigator, indicates that continued treatment with dasatinib is not in the best interest of the subject
Show all 30Show fewer
  • Imprisonment or the compulsory detention for treatment of either a psychiatric or physical (e.g., infectious disease) illness
  • Medical History and Concurrent Diseases
  • A serious uncontrolled medical disorder or active infection which would impair the ability of the patient to receive protocol therapy;
  • Uncontrolled angina within 3 months
  • Diagnosed or suspected congenital long QT syndrome
  • Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
  • Prolonged corrected QT(QTc) interval on pre-entry electrocardiogram (> 450 msec)
  • Uncontrolled hypertension
  • Dementia or altered mental status that would prohibit the understanding or rendering of informed consent;
  • History of significant bleeding disorder unrelated to CML, including:
  • Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
  • Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
  • Physical and Laboratory Test Findings
  • Total bilirubin ≥ 1.5 mg/dl
  • alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 2 times the institutional upper limits of normal
  • Serum creatinine ≥ 1.5 times the institutional upper limits of normal
  • Prohibited Therapies and/or Medications
  • Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes including:
  • quinidine, procainamide, disopyramide
  • amiodarone, sotalol, ibutilide, dofetilide
  • erythromycins, clarithromycin
  • chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
  • cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.
  • Medications that inhibit platelet function and any non-steroidal anti-inflammatory drug) or anticoagulants are prohibited unless a previous exception on CA180-002 was granted by the medical monitor. Subjects taking anagrelide for thrombocytosis due to CML are eligible for this protocol

About this study

Official title: Long-Term Safety and Efficacy of Dasatinib (BMS-354825) in Chronic Myelogenous Leukemia or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia in Subjects Who Experienced Clinical Benefit on Protocol CA180-002

To determine the long term safety and tolerability of dasatinib exposure in subjects previously treated in CA180-002.

Conditions
Leukemia
Being tested
Dasatinib
Medical subject headings
Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DasatinibDrug

    Also called BMS-354825, Sprycel, Src Kinase

    Tablets, Oral, The dosing ranges from 50mg to a total of 240mg daily with the following 3 schedules:

    • 5 days on, 2 days off
    • 6 days on, 1 day off
    • Continuous daily dosing

    Once Daily (QD) or Twice Daily (BID) dosing, Subjects will be treated until progression of disease despite escalation/reductions of dose to the level deemed safe by available data, until intolerable/unacceptable toxicity or until subject withdrawal from the study or discontinuation of the study

Study groups in NCT00978731
Study groupRoleWhat they receive
DasatinibExperimentalNot described
Receives: Drug: Dasatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Adverse Events (AEs) and AEs Leading to Study Drug Discontinuation.

    AEs: any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to AEs were recorded. These data differ from that in the Participant Flow section. This is because the data were collected on 2 different pages of the Case Report Form and were not reconciled.

    Measured: From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months.

  2. Number of Participants Who Experienced Drug-related AEs and Drug-related SAEs.

    Drug-related AEs are those events with a relationship to the study therapy of certain; probable; or possible or missing. Drug-related SAEs are those events with any relationship to the study therapy.

    Measured: From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months.

  3. Number of Participants With Grade 3-4 Hematology Abnormalities

    Abnormalities were graded per the National Cancer Institute(NCI)Common Toxicity Criteria (CTC), v3.0(Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are as follows: Hemoglobin: Grade 3:6.5 - <8.0g/dL, Grade 4: <6.5g/dL. Platelets: Grade 3: 25.0 - <50.0*10^9/L, Grade 4: <25.0*10. Absolute Neutrophil Count (ANC): Grade 3: 0.5 - <1.0*10^9/L, Grade 4: <0.5*10^9/L.White Blood Cells (WBC) : Grade 3: 1.0 - <2.0*10^9/L, Grade 4: <1.0*10^9/L.

    Measured: From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months.

  4. Number of Participants With Grade 3-4 Serum Chemistry Abnormalities

    Abnormalities were graded per the NCI (CTC), v3.0 (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are as follows: Alanine aminotransferase (ALT): Grade 3: 5.0-20.0 * ULN (upper limit of normal), Grade 4: >20.0 * ULN; Calcium: Grade 3: 6.0-<7.0 or >12.5-13.5 mg/dL, Grade 4: <0.6->13.5 mg/dL; Bilirubin: Grade 3: >3-10 * ULN, Grade 4: >10 * ULN; Creatinine: Grade 3: >3.0-6.0 * ULN, Grade 4: >6.0 * ULN; Albumin: Grade 3: <2g/dL (Grade 4 not defined in NCI CTC); Magnesium: Grade 3: 0.6-<0.8 or >2.46-6.6mEq/L, Grade 4: <0.6 or >6.6mEq/L.

    Measured: From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months.

  5. Number of Participants With Dose Interruptions and Dose Reductions

    Dose interruptions and reductions were allowed, in order to optimize individual participant's hematologic, cytogenetic, and molecular response while maintaining and evaluating safety and tolerability of long-term exposure to dasatinib. A dose reduction is defined as the administration of a dose at a lower level compared to previous dose and such that reduced dose, or a lower dose, is given at least 4 consecutive times. In determining the reductions, dose level would be compared to the previous non-null dose. Dose interruption is defined as a complete omission of dosing for 4 consecutive times.

    Measured: From start of study to final assessment (up to 32.2 months).

Secondary outcomes (7)

  1. Number of Participants With Complete Hematologic Response (CHR)

    CHR should meet all of the following criteria: WBC <= Institutional ULN; ANC >= 1000/mm^3 ; Platelets < 450 000/mm^3 , no blasts or promyelocytes in peripheral blood; < 5% myelocytes plus metamyelocytes in peripheral blood; basophils in peripheral blood < 20% and no extramedullary involvement (including no hepatomegaly or splenomegaly). CHR can begin only 14 days after the start of treatment.

    Measured: Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.

  2. Median Number of Months of CHR (Kaplan Meier Method)

    CHR: WBC<=ULN (range: 9.29-12.5*10^3 c\uL); ANC >=1000/mm^3;Platelets <450000/mm^3,no blasts/promyelocytes in peripheral blood; <5% myelocytes+metamyelocytes in peripheral blood; basophils in peripheral blood <20% \& no extramedullary involvement. Duration computed for chronic phase participants, measured in months from first day CHR criteria met, provided they are confirmed 4 weeks later, until progression of disease, treatment discontinuation due to progressive disease or death. Participants who neither discontinue due to progression, nor progress nor die censored on date of last assessment.

    Measured: Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.

  3. Number of Participants With Major Cytogenetic Response (MCyR)

    Cytogenetic responses are based on the prevalence of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a bone marrow sample. MCyR is defined as number of participants with Complete Cytogenetic Response (CCyR): 0% Ph+ cells in metaphase in bone marrow or Partial Cytogenetic Response (PCyR): >0% to 35% Ph+ cells in metaphase in bone marrow.

    Measured: Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.

  4. Median Number of Months of Major Cytogenetic Response (MCyR)

    MCyR: 0% Ph+ cells in metaphase in bone marrow or Partial Cytogenetic Response (PCyR): >0% to 35% Ph+ cells in metaphase in bone marrow.The duration of MCyR was computed for chronic phase participants whose best response is either CCyR or PCyR. It was measured in months from the time measurement criteria are first met for CCyR or PCyR (whichever status is recorded first) until the date of progression or death. Participants who neither progress nor die are censored on the date of their last cytogenetic assessment.

    Measured: Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.

  5. Number of Participants With Best Cytogenetic Response

    Cytogenetic responses are based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow sample. CCyR: 0% Ph+ cells in metaphase in bone marrow, PCyR: >0% to 35% Ph+ cells in metaphase in bone marrow, Minor CyR: >35% to 65% Ph+ cells in metaphase in bone marrow, Minimal CyR: >65% to 95% Ph+ cells in metaphase in bone marrow and No CyR: >95% to 100% Ph+ cells in metaphase in bone marrow.

    Measured: Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.

  6. Median Number of Months of Progression-free Survival (PFS) (Kaplan Meier Method)

    Interval between randomization date \& earliest date of disease progression/death due to any cause, assessed by the Independent Radiology Review Committee (IRRC) using modified World Health Organization (WHO) criteria to define progressive disease (PD): >=25% increase in sum of products of diameters (SOPD) of lesions compared with smallest SOPD recorded for study period or progression of any non-index lesion/appearance of new lesion. If no progression/death, date of last tumor assessment used. For participants who had no on-study tumor assessments \& were still alive, date of randomization used.

    Measured: Baseline to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.

  7. Median Number of Months of Overall Survival (OS) (Kaplan Meier Method)

    Overall survival was defined as the median number of months from baseline to death from any cause.

    Measured: Baseline to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Sep 2009 (estimated)
  2. Study startDec 2005
  3. Primary completionSep 2008
  4. Study completionSep 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00978731
Sponsor's protocol ID
CA180-039
Status last verified
Apr 2011
First submitted
16 Sep 2009
Last updated
28 Apr 2011
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Dasatinib in people with Leukemia, run by Bristol-Myers Squibb.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Apr 2011. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Apr 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Adverse Events (AEs) and AEs Leading to Study Drug Discontinuation. (time frame: From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months.). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00978731.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2011.

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