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

NCT02729961 | Withdrawn Phase 1 DMC FDA Drug

• 3 other identifiers: 9522NCI-2016-00396P30CA015704
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• Complete remission rate defined as the proportion of patients with CR according to the revised Response Criteria for Malignant Lymphoma

  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

  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

  Assessed using clinical assessment and computed tomography (CT)/positron emission tomography (PET) scans.

  Up to 3 years

Secondary Outcomes (4)

• Incidence of adverse events as assessed by NCI CTCAE version 4.03

  Up to 30 days

• Laboratory abnormalities as assessed by NCI CTCAE version 4.03

  Up to 3 years

• Overall survival (OS)

  From start of study treatment to date of death due to any cause, assessed up to 3 years

• Progression-free survival (PFS)

  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

Study Arms (1)

Treatment (brentuximab vedotin, ceritinib)

EXPERIMENTAL

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.

Drug: Brentuximab Vedotin; Drug: Ceritinib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Brentuximab Vedotin DRUG

Given IV

Also known as: ADC 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-35

Treatment (brentuximab vedotin, ceritinib)

Ceritinib DRUG

Given PO

Also known as: LDK 378, LDK378, Zykadia

Treatment (brentuximab vedotin, ceritinib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (brentuximab vedotin, ceritinib)

Pharmacological Study OTHER

Correlative studies

Treatment (brentuximab vedotin, ceritinib)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Lymphoma, Large-Cell, Anaplastic

Interventions

Brentuximab Vedotin; ceritinib

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• Andrei Shustov

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2016
• First Posted: April 6, 2016
• Study Start: January 3, 2018
• Primary Completion: July 1, 2023
• Study Completion: July 1, 2023
• Last Updated: October 10, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)