Ceritinib With Brentuximab Vedotin in Treating Patients With ALK-Positive Anaplastic Large Cell Lymphoma
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ClinicalTrials.gov Identifier: NCT02729961 |
Recruitment Status :
Withdrawn
(Administrative closure)
First Posted : April 6, 2016
Last Update Posted : October 10, 2019
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Anaplastic Large Cell Lymphoma, ALK-Positive CD30-Positive Neoplastic Cells Present Systemic Anaplastic Large Cell Lymphoma | Drug: Brentuximab Vedotin Drug: Ceritinib Other: Laboratory Biomarker Analysis Other: Pharmacological Study | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 0 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | January 3, 2018 |
Estimated Primary Completion Date : | July 1, 2023 |
Estimated Study Completion Date : | July 1, 2023 |

Arm | Intervention/treatment |
---|---|
Experimental: Treatment (brentuximab vedotin, ceritinib)
Patients 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.
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Drug: Brentuximab Vedotin
Given IV
Other Names:
Drug: Ceritinib Given PO
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Other: Pharmacological Study Correlative studies |
- 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 ]
- Maximum tolerated dose (MTD) of ceritinib and brentuximab vedotin based on incidence of dose limiting toxicity (DLT) assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 [ Time Frame: Up to 6 weeks ]
- Objective response rate defined as the proportion of patients with complete response (CR) or partial response (PR) according to the revised Response Criteria for Malignant Lymphoma [ Time Frame: Up to 3 years ]Assessed using clinical assessment and computed tomography (CT)/positron emission tomography (PET) scans.
- Incidence of adverse events as assessed by NCI CTCAE version 4.03 [ Time Frame: Up to 30 days ]
- Laboratory abnormalities as assessed by NCI CTCAE version 4.03 [ Time Frame: Up to 3 years ]
- Overall survival (OS) [ Time Frame: From start of study treatment to date of death due to any cause, assessed up to 3 years ]
- 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 ]Evaluate tumor lesion size in the determination of PFS by using Revised Response Criteria for Malignant Lymphoma (modified Cheson, 2011).

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Ages Eligible for Study: | 12 Years and older (Child, Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02729961
United States, Washington | |
Fred Hutch/University of Washington Cancer Consortium | |
Seattle, Washington, United States, 98109 |
Principal Investigator: | Andrei Shustov | Fred Hutch/University of Washington Cancer Consortium |
Responsible Party: | University of Washington |
ClinicalTrials.gov Identifier: | NCT02729961 |
Other Study ID Numbers: |
9522 NCI-2016-00396 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 9522 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium ) P30CA015704 ( U.S. NIH Grant/Contract ) |
First Posted: | April 6, 2016 Key Record Dates |
Last Update Posted: | October 10, 2019 |
Last Verified: | October 2019 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Lymphoma Lymphoma, Non-Hodgkin Lymphoma, Large-Cell, Anaplastic Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Lymphoma, T-Cell Antineoplastic Agents, Immunological Brentuximab Vedotin |
Ceritinib Antibodies Immunoglobulins Antibodies, Monoclonal Immunoconjugates Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |