Clinical Trials /

Ceritinib With Brentuximab Vedotin in Treating Patients With ALK-Positive Anaplastic Large Cell Lymphoma

NCT02729961

Description:

This phase I/II trial studies the side effects and best dose of ceritinib when given together with brentuximab vedotin to see how well they work in treating treatment-naive patients with anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma. Ceritinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as brentuximab vedotin, may interfere with the ability of tumor cells to grow and spread. Giving ceritinib together with brentuximab vedotin may be a better treatment for ALK-positive anaplastic large cell lymphoma.

Related Conditions:
  • Anaplastic Large Cell Lymphoma
Recruiting Status:

Withdrawn

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ceritinib With Brentuximab Vedotin in Treating Patients With ALK-Positive Anaplastic Large Cell Lymphoma
  • Official Title: A Phase I/II Open-Label Dose-Finding Study of Ceritinib Combined With Brentuximab Vedotin for Front-Line Treatment of ALK-Positive Anaplastic Large Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 9522
  • SECONDARY ID: NCI-2016-00396
  • SECONDARY ID: 9522
  • SECONDARY ID: P30CA015704
  • NCT ID: NCT02729961

Conditions

  • Anaplastic Large Cell Lymphoma, ALK-Positive
  • CD30-Positive Neoplastic Cells Present
  • Systemic Anaplastic Large Cell Lymphoma

Interventions

DrugSynonymsArms
Brentuximab VedotinADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35, Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35, cAC10-vcMMAE, SGN-35Treatment (brentuximab vedotin, ceritinib)
CeritinibLDK 378, LDK378, ZykadiaTreatment (brentuximab vedotin, ceritinib)

Purpose

This phase I/II trial studies the side effects and best dose of ceritinib when given together with brentuximab vedotin to see how well they work in treating treatment-naive patients with anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma. Ceritinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as brentuximab vedotin, may interfere with the ability of tumor cells to grow and spread. Giving ceritinib together with brentuximab vedotin may be a better treatment for ALK-positive anaplastic large cell lymphoma.

Detailed Description

      PRIMARY OBJECTIVES: I. To define a dose of ceritinib administered concurrently with
      brentuximab vedotin that has an acceptable toxicity profile (based on dose-limiting toxicity
      [DLT] rate) and sufficient efficacy (based on response rate) among patients with
      treatment-naive ALK-positive anaplastic large cell lymphoma (ALCL). SECONDARY OBJECTIVES: I.
      To assess the antitumor activity of ceritinib and brentuximab vedotin combination in
      treatment-naive patients with ALK-positive ALCL. II. To assess the utility of the molecular
      marker of ALK-positive ALCL in patient's plasma before, during and after therapy for disease
      risk assessment and post-treatment monitoring. OUTLINE: This is a phase I, dose-escalation
      study of ceritinib followed by a phase II study. Patients receive brentuximab vedotin
      intravenously (IV) over 30 minutes on day 1. Patients also receive ceritinib orally (PO) once
      daily (QD) on days 8-21 of course 1 and on days 1-21 for all subsequent courses. Treatment
      repeats every 21 days for up to 17 courses in the absence of disease progression or
      unacceptable toxicity. After completion of study treatment, patients are followed up every 3
      months up to 3 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (brentuximab vedotin, ceritinib)ExperimentalPatients receive brentuximab vedotin IV over 30 minutes on day 1. Patients also receive ceritinib PO QD on days 8-21 of course 1 and on days 1-21 for all subsequent courses. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
  • Brentuximab Vedotin
  • Ceritinib

Eligibility Criteria

        Inclusion Criteria:

          -  Treatment-naive systemic ALK-positive ALCL patients

          -  Histologically confirmed diagnosis of cluster of differentiation (CD)30-positive ALCL
             with documented ALK-positive status

          -  Fluorodeoxyglucose (FDG)-avid disease by positron emission tomography (PET) and
             dimensional measurable disease of at least 1.5 cm as documented by radiographic
             technique (spiral computed tomography [CT] preferred)

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 3

          -  Absolute neutrophil count (ANC) >= 1500/ul

          -  Platelet count >= 75,000/ul (unless documented bone marrow involvement with lymphoma)

          -  Hemoglobin (Hgb) >= 8 gr/dL

          -  Serum creatinine =< 1.5 x mg/dL and/or calculated creatinine clearance (using
             Cockcroft-Gault formula) >= 30 mL/min

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN), except for patients with
             Gilbert's syndrome or documented hepatic involvement with lymphoma who may be included
             if bilirubin =< 3.0 x ULN or direct bilirubin =< 1.5 x ULN

          -  Aspartate transaminase (AST) =< 3 x ULN, except with liver involvement by the lymphoma
             who are only included if AST =< 5 x ULN; alanine transaminase (ALT) < 3.0 x ULN,
             except with liver involvement by the lymphoma who are only included if AST =< 5 x ULN

          -  Alkaline phosphatase (ALP) =< 5.0 x ULN

          -  Fasting plasma glucose =< 175 mg/dL (=< 9.8 mmol/L)

          -  Serum amylase =< 2 x ULN

          -  Serum lipase =< ULN

          -  Patients must have the following laboratory values or have the following laboratory
             values corrected to be within normal limits before the first dose of ceritinib: *
             Potassium * Magnesium * Phosphorus * Total calcium (corrected for serum albumin)

          -  Females of child bearing potential, defined as all women physiologically capable of
             becoming pregnant, must have a negative serum or urine beta human chorionic
             gonadotropin (b-hCG) pregnancy test results within 7 days prior to the first dose of
             study treatment, and must agree to use highly effective methods of contraception
             during dosing and for 3 months after the last dose of study treatment; highly
             effective methods of contraception include: * Total abstinence (when this is in line
             with the preferred and usual lifestyle of the subject; periodic abstinence (e.g.,
             calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not
             acceptable methods of contraception * 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 by follow up hormone level
             assessment * Male sterilization (at least six months prior to screening) with the
             appropriate post-vasectomy documentation of absence of sperm in the ejaculate; for
             female subjects on the study the vasectomized male partner should be sole partner for
             that subject * Combination of any two of the following: ** 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 ** Placement of an intrauterine device (IUD) or
             intrauterine system (IUS) ** Barrier methods of contraception: condom or occlusive cap
             (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal
             suppository * In case of use of oral contraception, women should have been stable on
             the same pill for a minimum of 3 months before taking study treatment * Women are
             considered post-menopausal and not of child bearing potential if they have had 12
             months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g.,
             age appropriate, history of vasomotor symptoms) or who have had a bilateral tubal
             ligation or hysterectomy

          -  Sexually active males must agree to use a condom during intercourse while receiving
             and for 3 months after the last dose of study treatment; male patients should not
             father a child for 3 months after the last dose of study treatment; a condom is
             required to be used also by vasectomized men in order to prevent delivery of the drug
             via seminal fluid

          -  Patients or their legally authorized representative must have the ability to
             understand and provide signed informed written consent

          -  Patients must express willingness and ability to comply with scheduled visits,
             treatment plans, laboratory tests and other study procedures

        Exclusion Criteria:

          -  Known hypersensitivity to any of the excipients of ceritinib (microcrystalline
             cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate)

          -  Known prior history of interstitial pneumonitis, including clinically significant
             radiation pneumonitis (i.e. affecting activities of daily living or requiring
             therapeutic intervention)

          -  Impaired gastrointestinal (GI) function or GI disease that may significantly alter the
             absorption of ceritinib (e.g. ulcerative disease, uncontrolled nausea, vomiting,
             diarrhea, or malabsorption syndrome) or inability to swallow up to five ceritinib
             capsules daily

          -  History of pancreatitis or history of increased amylase or lipase that was due to
             pancreatitis

          -  Other severe, acute, or chronic medical condition including uncontrolled diabetes
             mellitus or psychiatric condition or laboratory abnormalities that, in the opinion of
             the investigator, may increase risk associated with study participation or may
             interfere with the interpretation of study results

          -  Major surgery (e.g. intra-abdominal, intra-thoracic or intra-pelvic) within 4 weeks
             prior to starting study treatment or lack of recovery from side effects of such
             procedure; video-assisted thoracic surgery (VATS) and mediastinoscopy will not be
             counted as major surgery and patients can receive study treatment >= 1 week after
             these procedures

          -  History of another primary malignancy that has not been in remission for at least 3
             years (the following malignancies are exempt from the 3 year limit: non-melanoma skin
             cancer, fully-excised melanoma in situ [stage 0], curatively treated, localized
             prostate cancer, and cervical carcinoma in situ in biopsy or a squamous
             intraepithelial lesion on Papanicolau [PAP] smear)

          -  Known cerebral/meningeal disease

          -  Clinically significant, uncontrolled heart disease and/or recent cardiac event (within
             6 months), such as: * Unstable angina * Myocardial infarction * History of documented
             congestive heart failure (New York Heart Association functional classification III-IV)
             * Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 160 mm Hg
             and/or diastolic blood pressure (DBP) >= 100 mm Hg, with or without antihypertensive
             medication * Ventricular arrhythmias, or supraventricular/nodal arrhythmias not
             controlled with medications; other cardiac arrhythmias not controlled with medications
             * Left ventricular ejection fraction < 20% corrected QT (QTcF) > 470 ms using
             Fridericia's correction on the screening electrocardiogram (ECG) * Initiation or
             adjustment of antihypertensive medication(s) is allowed prior to screening

          -  Any active grade 3 or higher (per the National Cancer Institute [NCI] Common
             Terminology Criteria for Adverse Events [CTCAE], version 4.03) viral, bacterial, or
             fungal) infection within two weeks prior to the first dose of study treatment

          -  Receiving medications that meet one of the following criteria and that cannot be
             discontinued at least 1 week prior to the start of treatment with ceritinib and for
             the duration of participation: * Medication with a known risk of prolonging the QT
             interval or inducing Torsades de Pointes * Strong inhibitors or strong inducers of
             cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5) * Medications with
             a low therapeutic index that are primarily metabolized by CYP3A4/5, and/or cytochrome
             P450, family 2, subfamily C, polypeptide 9 (CYP2C9) * Therapeutic doses of warfarin
             sodium (Coumadin) or any other Coumadin-derived anti-coagulant; anticoagulants not
             derived from warfarin are allowed (e.g., dabigatran, rivaroxaban, apixaban) * Unstable
             or increasing doses of corticosteroids; if patients are on corticosteroids for
             endocrine deficiencies or tumor-associated symptoms (non-central nervous system
             [CNS]), dose must have been stabilized (or decreasing) for at least 5 days before
             first dose of study treatment * Enzyme-inducing anticonvulsive agents * Herbal
             supplements

          -  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 positive
             b-hCG laboratory test
      
Maximum Eligible Age:N/A
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete remission rate defined as the proportion of patients with CR according to the revised Response Criteria for Malignant Lymphoma
Time Frame:Up to 3 years
Safety Issue:
Description:Assessed using clinical assessment and computed tomography (CT)/positron emission tomography (PET) scans.

Secondary Outcome Measures

Measure:Incidence of adverse events as assessed by NCI CTCAE version 4.03
Time Frame:Up to 30 days
Safety Issue:
Description:
Measure:Laboratory abnormalities as assessed by NCI CTCAE version 4.03
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:From start of study treatment to date of death due to any cause, assessed up to 3 years
Safety Issue:
Description:
Measure:Progression-free survival (PFS)
Time Frame:From start of treatment to first documentation of objective tumor progression or to death due to any cause, whichever comes first, assessed up to 3 years
Safety Issue:
Description:Evaluate tumor lesion size in the determination of PFS by using Revised Response Criteria for Malignant Lymphoma (modified Cheson, 2011).

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Washington

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