Clinical Trials /

Treatment-free Remission After Achieving Sustained MR4.5 on Nilotinib (ENESTop)

NCT01698905

Description:

A clinical research study to find out if it is safe to stop the drug nilotinib (Tasigna) in chronic myeloid leukemia (CML) patients. Patients who started treatment with imatinib (Gleevec) when they were first diagnosed with CML, then switched to nilotinib (Tasigna) for at least 2 years with the combined time on imatinib (Gleevec) and nilotinib (Tasigna) for at least 3 years and have very small amount of leukemia cells remaining after the nilotinib (Tasigna) treatment will qualify for the study.

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Treatment-free Remission After Achieving Sustained MR4.5 on <span class="go-doc-concept go-doc-intervention">Nilotinib</span> (ENESTop)

Title

  • Brief Title: Treatment-free Remission After Achieving Sustained MR4.5 on Nilotinib (ENESTop)
  • Official Title: A Phase II, Single Arm, Open Label Study of Treatment-free Remission in Chronic Myeloid Leukemia (CML) Chronic Phase (CP) Patients After Achieving Sustained MR4.5 on Nilotinib
  • Clinical Trial IDs

    NCT ID: NCT01698905

    ORG ID: CAMN107A2408

    Trial Conditions

    Chronic Myeloid Leukemia

    Trial Interventions

    Drug Synonyms Arms
    nilotinib nilotinib

    Trial Purpose

    A clinical research study to find out if it is safe to stop the drug nilotinib (Tasigna) in
    chronic myeloid leukemia (CML) patients. Patients who started treatment with imatinib
    (Gleevec) when they were first diagnosed with CML, then switched to nilotinib (Tasigna) for
    at least 2 years with the combined time on imatinib (Gleevec) and nilotinib (Tasigna) for at
    least 3 years and have very small amount of leukemia cells remaining after the nilotinib
    (Tasigna) treatment will qualify for the study.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    nilotinib Experimental 70 patients who maintain MR4.5 during the one year nilotinib consolidation phase will stop treatment when they enter the treatment-free remission (TFR) phase nilotinib

    Eligibility Criteria

    Inclusion Criteria:

    1. Male or female patients >= 18 years of age

    2. ECOG Performance Status of 0, 1, or 2

    3. Patient with diagnosis of BCR-ABL positive CML CP

    4. Patient has received a minimum of 3 years of tyrosine kinase inhibitor treatment
    (first with imatinib (> 4 weeks) and then switched to nilotinib) since initial
    diagnosis

    5. Patient has at least 2 years of nilotinib treatment prior to study entry.

    6. Patient has achieved MR4.5 (local laboratory assessment) during nilotinib treatment,
    and determined by a Novartis designated central PCR lab assessment at screening

    7. Adequate end organ function as defined by:

    - Direct bilirubin 1.5 x ULN except for i) patient with documented Gilbert's
    syndrome for whom any bilirubin value is allowed and ii) for patients with
    asymptomatic hyperbilirubinemia (liver transaminases and alkaline phosphatase
    within normal range)

    - SGOT(AST) and SGPT(ALT) < 3 x ULN (upper limit of normal)

    - Serum lipase 2 x ULN

    - Alkaline phosphatase 2.5 x ULN

    - Serum creatinine < 1.5 x ULN

    8. Patients must have the following electrolyte values LLN (lower limit of normal)
    limits or corrected to within normal limits with supplements prior to the first dose
    of study medication:

    - Potassium

    - Magnesium

    - Total calcium (corrected for serum albumin)

    9. Patients must have normal marrow function as defined below:

    - Absolute Neutrophil Count (ANC) 1.5 x 109/L

    - Platelets 100 x 109/L

    - Hemoglobin 9.0 g/dL

    10. Written informed consent obtained prior to any screening procedures

    Exclusion Criteria:

    1. Prior AP, BC or allo-transplant

    2. Patient has documented MR4.5 at the time when switched from imatinib to nilotinib

    3. Patients with known atypical transcript

    4. CML treatment resistant mutation(s) (T315I, E255K/V, Y253H, F359C/V) detected if a
    testing was done in the past (there is no requirement to perform mutation testing at
    study entry if it was not done in the past)

    5. Dose reductions due to neutropenia or thrombocytopenia in the past 6 months

    6. Patient ever attempted to permanently discontinue imatinib or nilotinib treatment

    7. Known impaired cardiac function including any one of the following:

    - Inability to determine the QT interval on ECG

    - Complete left bundle branch block

    - Long QT syndrome or a known family history of long QT syndrome

    - History of or presence of clinically significant ventricular or atrial
    tachyarrhythmias

    - Clinically significant resting bradycardia

    - QTcF > 480 msec

    - History or clinical signs of myocardial infarction within 1 year prior to study
    entry

    - History of unstable angina within 1 year prior to study entry

    - Other clinically significant heart disease (e.g. uncontrolled congestive heart
    failure or uncontrolled hypertension)

    8. Severe and/or uncontrolled concurrent medical disease that in the opinion of the
    investigator could cause unacceptable safety risks or compromise compliance with the
    protocol (e.g. uncontrolled diabetes (defined as HbA1c > 9%), uncontrolled infection)

    9. History of acute pancreatitis within 1 year prior to study entry or past medical
    history of chronic pancreatitis

    10. Known presence of a significant congenital or acquired bleeding disorder unrelated to
    cancer

    11. History of other active malignancy within 5 years prior to study entry with the
    exception of previous or concomitant basal cell skin cancer, previous cervical
    carcinoma in situ treated curatively

    12. Patients who have not recovered from prior surgery

    13. Treatment with other investigational agents (defined as not used in accordance with
    the approved indication) within 4 weeks of Day 1

    14. Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers,
    and the treatment cannot be either discontinued or switched to a different medication
    prior to study entry. See Appendix 14.1 for a list of these medications. This list
    may not be comprehensive.

    15. Patients actively receiving therapy with herbal medicines that are strong CYP3A4
    inhibitors and/or inducers, and the treatment cannot be either discontinued or
    switched to a different medication prior to study entry. These herbal medicines may
    include Echinacea, (including E. purpurea, E. angustifolia and E. pallida), Piperine,
    Artemisinin, St. John's Wort, and Ginkgo.

    16. Patients who are currently receiving treatment with any medications that have the
    potential to prolong the QT interval and the treatment cannot be either safely
    discontinued or switched to a different medication prior to study entry. (Please see
    www.azcert.org/medical-pros/drug-lists/printable-drug-list.cfm for a list of agents
    that prolong the QT interval.)

    17. Impairment of gastrointestinal (GI) function or GI disease that may significantly
    alter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea,
    vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass
    surgery)

    18. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
    female after conception and until the termination of gestation, confirmed by a
    positive hCG laboratory test.

    19. Women of child-bearing potential, defined as all women physiologically capable of
    becoming pregnant, must have a negative serum pregnancy test before initiation of
    study treatment and must also use highly effective methods of contraception while
    enrolled in the study. The use of highly effective contraception should continue for
    at least 14 days after the last dose of study treatment or until the last day of
    TFR/TFR-2, or for the duration of a monthly cycle of oral contraception, whichever is
    longer. Acceptable forms of highly effective contraception methods include:

    a. Total abstinence (when this is in line with the preferred and usual lifestyle of
    the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal,
    post-ovulation methods) and withdrawal are not acceptable methods of contraception
    and male/female sterilization defined as:

    - Female sterilization (have had surgical bilateral oophorectomy with or without
    hysterectomy) or tubal ligation at least six weeks before taking study
    treatment. In case of oophorectomy alone, only when the reproductive status of
    the woman has been confirmed and documented by follow up hormone level
    assessment

    - Male sterilization (at least 6 months prior to screening). For female patients
    on the study, study participation assumes the vasectomized male partner is the
    sole partner for that patient or b. A combination of any two of the following
    (i+ii or i+iii or ii+iii): i) Barrier methods of contraception: condom or
    occlusive cap (diaphragm or cervical/vault caps) with spermicidal
    foam/gel/film/cream/ vaginal suppository ii) Use of oral, injected or implanted
    hormonal methods of contraception or other forms of hormonal contraception that
    have comparable efficacy (failure rate <1%), for example hormone vaginal ring or
    transdermal hormone contraception iii) Placement of an intrauterine device (IUD)
    or intrauterine system (IUS)

    Minimum Eligible Age: N/A

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    No documented confirmed loss of MR4, no documented loss of MMR and no re-starting of nilotinib therapy

    Secondary Outcome Measures

    No documented confirmed loss of MR4, no documented loss of MMR and no re-starting of nilotinib therapy in the first 24, 36, and 48 months following nilotinib cessation.

    Progression to AP/BC or death where the "failure" event is the earliest occurrence of the following event: progression to AP/BC or death from any cause.

    Treatment free survival (TFS) defined as lack any of the following events: loss of MMR, confirmed loss of MR4, re-start of Nilotinib treatment, progression to AP/BC or death from any cause.

    Overall survival (OS) defined as the time from the date of cessation of nilotinib therapy to the date of death from any cause.

    BCR-ABL transcript changes within 12 months after re-start of nilotinib therapy

    Trial Keywords

    Phase II, single arm, open label, nilotinib, treatment-free remission, MR4.5, confirmed loss of MR4, loss of MMR, Ph+ CML-CP