Clinical Trials /

Novartis PhII Ceritinib (LDK378) in R/R ALK+ Hem Malignancies

NCT02343679

Description:

This is a phase II, single arm, unblinded study of ceritinib in patients with rel/ref hematologic malignancies. Up to 24 evaluable subjects will be enrolled with an interim analysis for efficacy after the first 9 subjects are enrolled. Any subject who takes at least one dose of study drug will be evaluable for safety. Only subjects who complete at least 1 cycle of study drug and have clear progression on physical exam or have had at least one restaging study will be considered evaluable for response. Each subject will receive the same dose of 750mg po daily at the study entry. Subjects with stable disease or better will be allowed to continue study drug until disease progression or until intolerable adverse events or patient or physician decision. Intrapatient dose reductions will be allowed for adverse events. This is a multicenter study with Duke as the lead site. Blood and tissue samples, will be collected and used for exploratory analysis.

Related Conditions:
  • Mature B-Cell Lymphoma/Leukemia
  • Mature T-Cell and NK-Cell Lymphoma/Leukemia
Recruiting Status:

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

Novartis PhII <span class="go-doc-concept go-doc-intervention">Ceritinib (LDK378)</span> in R/R <span class="go-doc-concept go-doc-biomarker">ALK</span>+ Hem Malignancies

Title

  • Brief Title: Novartis PhII Ceritinib (LDK378) in R/R ALK+ Hem Malignancies
  • Official Title: A Phase II Study of the ALK Inhibitor, Ceritinib (LDK378), in Relapsed/Refractory ALK+ Hematologic Malignancies
  • Clinical Trial IDs

    NCT ID: NCT02343679

    ORG ID: Pro00056623

    Trial Conditions

    Hematologic Malignancies

    Trial Interventions

    Drug Synonyms Arms
    ceritinib LDK378 Ceritinib for ALK + patients

    Trial Purpose

    This is a phase II, single arm, unblinded study of ceritinib in patients with rel/ref
    hematologic malignancies. Up to 24 evaluable subjects will be enrolled with an interim
    analysis for efficacy after the first 9 subjects are enrolled. Any subject who takes at
    least one dose of study drug will be evaluable for safety. Only subjects who complete at
    least 1 cycle of study drug and have clear progression on physical exam or have had at least
    one restaging study will be considered evaluable for response. Each subject will receive the
    same dose of 750mg po daily at the study entry. Subjects with stable disease or better will
    be allowed to continue study drug until disease progression or until intolerable adverse
    events or patient or physician decision. Intrapatient dose reductions will be allowed for
    adverse events. This is a multicenter study with Duke as the lead site. Blood and tissue
    samples, will be collected and used for exploratory analysis.

    Detailed Description

    This is a phase II, single arm, unblinded study of ceritinib in patients with rel/ref
    hematologic malignancies. Up to 24 evaluable subjects will be enrolled with an interim
    analysis for efficacy after the first 9 subjects are enrolled. Any subject who takes at
    least on dose of study drug will be evaluable for safety. Only subjects who complete at
    least 1 cycle of study drug and have clear progression on physical exam or have had at least
    one restaging study will be considered evaluable for response. Each subject will receive the
    same dose of 750mg po daily at the study entry. Subjects with stable disease or better will
    be allowed to continue study drug until disease progression or until intolerable adverse
    events or patient or physician decision. Intrapatient dose reductions will be allowed for
    adverse events. Blood and tissue samples, will be collected and used for exploratory
    analysis.

    Dose Level 0 (starting dose) 750mg/day Dose level -1 600mg/day Dose level -2 450mg/day

    Baseline evaluations are to be conducted within 30 days prior to start of protocol therapy
    unless otherwise noted in the time to events table. Scans and x-rays must be performed
    within six weeks prior to the start of therapy. Bone marrow biopsy must be performed within
    twelve weeks prior to starting therapy. In the event that the patient's condition is
    deteriorating, laboratory evaluations should be repeated within 48 hours prior to initiation
    of the next cycle of therapy. All the labs have to be within the study eligibility range
    prior to the start of study treatment.

    All visits should occur within 3 days before or after the scheduled day of the visit. An
    early or late visit will not shorten or extend the duration of that cycle - all cycles will
    be 28 days.

    If study drug is held for any reason then the missed days should still be counted as a day
    in the cycle. However, if the study drug is on hold when a 28 day cycle ends, then day 1 of
    the next cycle and the necessary evaluations should not be started until drug is restarted.
    Therefore, the cycle during which a drug is held could potentially have more than 28 days.

    Patients will be followed for up to 2 years after completion of therapy or until progression
    of disease or death, whichever comes first. In follow up, patients will be seen every 3
    months for physical exam, lab draws for the first two years after completing all study drugs
    or until alternative therapy is begun or until progression of disease or death-whichever
    comes first. Radiographic imaging will be performed every 6 months for the first two years
    after study drug is completed.

    Patients removed from study for unacceptable adverse events will be followed until
    resolution or stabilization of the adverse event and will continue to be followed until
    progression of disease or death. Unacceptable adverse events are those that lead to stopping
    of a study drug and for which there is no resolution of drug related toxicity after a 6 week
    washout period so that the subject is removed from study as defined in section 6.

    Patients removed from the study due to progressive disease will be followed until resolution
    or stabilization of any adverse events due to the agents, after which their follow up will
    be completed.

    At a minimum, all patients who discontinue ceritinib treatment, including those who refuse
    to return for a final visit, will be contacted for safety evaluations during the 30 days
    following the last dose of treatment

    Trial Arms

    Name Type Description Interventions
    Ceritinib for ALK + patients Experimental all ALK + hematologic malignancies patients will receive ceritinib ceritinib

    Eligibility Criteria

    Inclusion Criteria:

    - Alk+R/R hematologic malignancy including but not limited to ALK+ALCL or ALK+LBCL > 1
    prior standard cytotoxic regimen

    - Age >18

    - ECOG performance status <2

    - Evidence of measurable or evaluable disease

    - Toxicities grade 2 due to prior therapies Exception: any grade alopecia

    - Platelets >75 x 109/L

    - ANC>1.5 x 109/L

    - AST/ALT<3.0 x ULN, except liver involvement by their lymphoma, include if AST/ALT<5 x
    ULN.

    - Total Bilirubin<1.5 x ULN, (includes gilbert's syndrome if total bilirubin <3.0 x ULN
    and direct bilirubin <1.5 x ULN)

    - Potassium, magnesium, total calcium and phosphorous > lower limits of normal

    - Calculated or measured CrCl> 30ml/min

    - Ability to provide written informed consent

    - Willing/able to comply with scheduled visits, treatment plans, laboratory tests and
    other procedures

    - Women/men of reproductive potential must agree to use effective birth control during
    study and for 3 months after receiving study drug.

    - Must have existing tissue available for correlative studies

    Exclusion Criteria:

    - No chemotherapy, radiation or surgical resection of malignancy < 3 weeks before start
    of study drug

    - Prior therapy with other ALK inhibitor investigational agents except crizotinib

    - Active, uncontrolled, serious infection or medical or psychiatric illness likely to
    interfere with trial

    - Known HIV infection

    - Extensive disseminated bilateral interstitial fibrosis or interstitial lung disease,
    (history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia,
    obliterative bronchiolitis or clinically significant radiation pneumonitis) i.e.
    affecting daily living or requiring ongoing therapeutic intervention.

    - Symptomatic CNS metastases and neurologically unstable or increasing doses of
    steroids < 2 weeks prior to study entry

    - Major surgery 4 weeks before initiating protocol therapy.

    - Hypersensitivity to microcrystalline cellulose, mannitol, crospovidone, colloidal
    silicon dioxide, magnesium stearate

    - Diagnosis or treatment for malignancy other than NHL < 3 years before Day 1 of
    protocol therapy. Exceptions:

    - Basal or squamous cell carcinoma of the skin

    - In situ malignancy - completely resected.

    - Prostate cancer treated with prostatectomy or radiotherapy > 2 years before Day
    1 of protocol therapy and PSA is undetectable

    - In situ malignancy - completely resected

    - Current treatment with another investigational agent < 14 days before enrollment.
    Other non-treatment studies allowed if it won't interfere with study participation.

    - Myocardial infarction or unstable angina 6 months before enrollment or New York
    Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina,
    severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of
    acute ischemia or active conduction system abnormalities.

    o QTcF>450msec

    - Oral steroids > 4mg dexamethasone or equivalent/day excluding steroids used for
    adrenal insufficiency

    - Impaired GI function from significant small bowel resection or gastric bypass surgery
    or inability to swallow up to five ceritinib capsules daily

    - Ongoing GI adverse events > grade 2 (e.g. nausea, vomiting, or diarrhea) at start of
    study.

    - Receiving medications that meet one of the following criteria and that cannot be
    discontinued at least 1 week prior to start of treatment and for the duration of
    participation:

    - Medication with a significant known risk of prolonging the QT interval or
    inducing Torsades de Pointes
    http://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm

    - Strong inhibitors or strong inducers of CYP3A4/5
    http://medicine.iupui.edu/flockhart/table.htm or
    http://www.druginteractioninfo.org

    - Therapeutic doses of warfarin sodium (Coumadin) or coumadin-derived
    anti-coagulant.

    - Enzyme-inducing anticonvulsive agents

    - Herbal supplements

    - Pregnant or nursing (lactating) women

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Overall Response Rate (ORR)

    Secondary Outcome Measures

    Progression Free Survival (PFS)

    Trial Keywords