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Open-Label Study Evaluating Dasatinib Therapy Discontinuation in Patients With Chronic Phase Chronic Myeloid Leukemia With Stable Complete Molecular Response

NCT01850004

Description:

The study purpose is to test the hypothesis that Chronic Phase Chronic Myeloid Leukemia (CP-CML) patients with stable Complete Molecular Response (CMR) who discontinue Dasatinib treatment are able to maintain a sustained remission in the long-term, with undetectable or minimally detectable BCR-ABL residual disease.

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Open-Label Study Evaluating <span class="go-doc-concept go-doc-intervention">Dasatinib</span> Therapy Discontinuation in Patients With Chronic Phase <span class="go-doc-concept go-doc-disease">Chronic Myeloid Leukemia</span> With Stable Complete Molecular Response

Title

  • Brief Title: Open-Label Study Evaluating Dasatinib Therapy Discontinuation in Patients With Chronic Phase Chronic Myeloid Leukemia With Stable Complete Molecular Response
  • Official Title: Open-Label Single Arm Phase 2 Study Evaluating Dasatinib Therapy Discontinuation In Patients With Chronic Phase Chronic Myeloid Leukemia (CP-CML) With Stable Complete Molecular Response (CMR) DASFREE
  • Clinical Trial IDs

    NCT ID: NCT01850004

    ORG ID: CA180-406

    NCI ID: 201200142127

    Trial Conditions

    Chronic Phase Chronic Myeloid Leukemia

    Trial Interventions

    Drug Synonyms Arms
    Dasatinib Sprycel Dasatinib

    Trial Purpose

    The study purpose is to test the hypothesis that Chronic Phase Chronic Myeloid Leukemia
    (CP-CML) patients with stable Complete Molecular Response (CMR)who discontinue Dasatinib
    treatment are able to maintain a sustained remission in the long-term, with undetectable or
    minimally detectable BCR-ABL residual disease.

    Detailed Description

    Primary Purpose: Protocol designed to evaluate remission of disease after treatment
    discontinuation. Treatment re-started if relapse occurs

    Trial Arms

    Name Type Description Interventions
    Dasatinib Experimental Dasatinib 20, 50, 80, 100 and 140 mg tablets by mouth, once daily, up to 60 months Dasatinib

    Eligibility Criteria

    For more information regarding BMS clinical trial participation, please visit
    www.BMSStudyConnect.com

    Inclusion Criteria:

    - Signed Written Informed Consent

    a. Patients must be informed of the investigational nature of this study and of
    alternative standard therapeutic options and must provide written informed consent

    - Target Population

    1. Men and women diagnosed with CP-CML, on treatment with dasatinib for a minimum
    of 2 years at the time of enrollment and in dasatinib -induced complete
    molecular remission (defined as 0.0032% or 4.5 log reduction of BCR-ABL
    transcript as determined by local standards) ongoing for at least 1 year prior
    to study entry

    1. Patients are eligible for the screening assessment from the central lab if
    they have been in stable dasatinib induced CMR for a minimum of nine months,
    documented by at least three assessments, conducted 2 - 6.5 months apart, at a
    local lab. The first screening assessment conducted at the central lab will be
    repeated after three months, if the first assessment confirms CMR (MR 4.5).
    Patients are eligible for enrollment if both assessments from the central lab
    confirm MR4.5. For any patient not eligible for enrollment on the basis of a
    central laboratory test that does not confirm CMR, rescreening is allowed 9
    months after (or longer) from the last central lab screening failure. These
    patients must have documented stable CMR at the local lab, and must meet all
    other criteria, before rescreening.

    2. Subjects who have received dasatinib beyond first or second line treatment and
    meet other enrollment criteria are eligible for the study provided prior
    Tyrosine-kinase inhibitors (TKI) were discontinued due to intolerance or lack
    efficacy, although only one instance of lack of efficacy to TKI is allowed.

    3. Eastern Co-Operative Group (ECOG) Performance Status (PS) of 0-1

    4. Life expectancy of > 1 year

    5. Adequate renal function defined as serum creatinine 3.0 times the
    institutional ULN

    6. Adequate hepatic function defined as: total bilirubin 3.0 times the
    institutional ULN; alanine aminotransferase (ALT) and aspartate aminotransferase
    (AST) 5 times the institutional upper limit of normal (ULN). In cases where
    the patient needs to restart dasatinib therapy, caution will be used in case of
    hepatic impairment.

    7. Serum Na, K, Mg, and total serum Ca or ionized Ca levels must be greater than or
    equal to the institutional lower limit of normal. Patients with low K, Mg
    levels, total serum Ca and/or ionized Ca may be repleted to allow for protocol
    entry. Rescreening is permitted in the event of temporary biochemical
    abnormalities.

    - Age and Reproductive Status

    1. Men and women, ages 18

    2. Women of childbearing potential (WOCBP) must have a negative serum or urine
    pregnancy test [minimum sensitivity 25 IU/L or equivalent units of Human
    Chorionic Gonadotropin (HCG)] within 24 hours prior to the restart of study drug

    3. Women must not be breastfeeding

    4. WOCBP must agree to follow instructions for method(s) of contraception at the
    restart of treatment with study drug (dasatinib) and for the duration treatment
    plus 30 days (duration of ovulatory cycle) for a total of 30 days post-treatment
    completion

    5. Men who are sexually active with WOCBP must agree to follow instructions for
    method(s) of contraception for 90 days after study entry (withdrawal of
    dasatinib), at restart of study drug (dasatinib) and for the duration of
    treatment with study drug (dasatinib) plus 90 days (duration of sperm turnover)
    for a total of 90 days post-treatment completion

    Investigators shall counsel WOCBP and male subjects who are sexually active with
    WOCBP on the importance of pregnancy prevention and the implications of an
    unexpected pregnancy. Investigators shall advise WOCBP and male subjects who are
    sexually active with WOCBP on the use of highly effective methods of
    contraception. Highly effective methods of contraception have a failure rate of
    < 1% per year when used consistently and correctly

    At a minimum, subjects must agree to the use of two methods of contraception,
    with one method being highly effective and the other method being either highly
    effective or less effective

    6. Azoospermic males and WOCBP who are continuously not heterosexually active are
    exempt from contraceptive requirements. However WOCBP must still undergo
    pregnancy testing as described in these sections

    Exclusion Criteria:

    - Target Disease Exceptions

    1. Patients who have not achieved a 1-log reduction in BCR-ABL transcript levels
    compared with baseline as determined by local standards or > 10% IS
    [International Standard]) documented at 3.0-6.5 months since the initial start
    of dasatinib therapy.

    2. Patients who have previously undergone hematopoietic stem cell transplantation
    (SCT) or who are scheduled for SCT

    3. Previous diagnosis of CML accelerated phase or blast crisis

    - Medical History and Concurrent Diseases

    1. Prior or concurrent malignancy, except the following:

    - Curatively treated basal cell or squamous cell skin cancer

    - Cervical carcinoma in situ

    - Adequately treated Stage I or II cancer from which the subject is currently
    in complete remission

    - Any other cancer from which the subject has been disease free for 3 years

    2. A serious uncontrolled medical disorder or active infection that would impair
    the ability of the subject to receive protocol therapy in case re-initiation of
    dasatinib is needed.

    3. Uncontrolled or significant cardiovascular disease, including any of the
    following:

    - Diagnosed or suspected congenital long QT syndrome

    - Any history of significant ventricular arrhythmias for example ventricular
    tachycardia (BT), ventricular fibrillation (VF), and Torsade de Points
    (TdP)

    - Prolonged QT Interval Corrected (QTc) interval on pre-entry
    electrocardiogram that is considered clinically significant according to
    investigator's criteria

    - Any history of second- or third-degree heart block (may be eligible if the
    subject currently has a pacemaker)

    4. Subjects with prior history of pericardial effusion or pleural effusion that
    required thoracentesis are excluded. Subjects with prior history of pericardial
    or pleural effusion that was clinically manageable and a maintained CMR for 1
    year on a stable dose of dasatinib are allowed.

    5. 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

    - Allergies and Adverse Drug Reaction

    a. Subjects with known hypersensitivity to excipients of Dasatinib tablets (Tablet
    core:lactose monohydrate, microcrystalline cellulose, croscarmellose sodium;
    hydroxypropyl cellulose, magnesium stearate; Film-coating: hypromellose titanium
    dioxide macrogol 400)

    - Sex and Reproductive Status

    1. Patients who are pregnant or breastfeeding or likely to become pregnant

    2. Men whose partner is unwilling or unable to avoid pregnancy

    - Other Exclusion Criteria

    1. Patients with a history of non-compliance to CML treatment and monitoring
    requirements

    2. Prisoners or subjects who are involuntarily incarcerated

    3. Subjects who are compulsorily detained for treatment of either a psychiatric or
    physical (eg, infectious disease) illness

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    MMR rate at 12 months

    Secondary Outcome Measures

    Event-free survival (EFS) after Dasatinib discontinuation

    Relapse-free survival (RFS) after Dasatinib discontinuation

    Assessment of BCR-ABL kinetics for subjects who experience loss of Complete Molecular Response (CMR) but not MMR

    Assessment of BCR-ABL kinetics in subjects in CMR or less with measurable levels

    Rate of transformation to AP/BC

    Progression Free Survival (PFS)

    Rate of transformation to OS

    Trial Keywords