Safety and Efficacy Study of Loncastuximab Tesirine + Ibrutinib in Diffuse Large B-Cell or Mantle Cell Lymphoma

Stopped early · Phase 1/Phase 2

Conditions studied: Diffuse Large B-Cell Lymphoma, Mantle Cell Lymphoma

In brief

The purpose of this Phase 1/2 study is to evaluate the safety and efficacy of Loncastuximab Tesirine (ADCT-402) in combination with Ibrutinib in participants with Advanced Diffuse Large B-Cell Lymphoma or Mantle Cell Lymphoma.

Key facts

Study ID

NCT03684694

Run by

ADC Therapeutics S.A.

People needed

136

Starts

2018-12-01

Expected to finish

2022-11-08

Last updated by the study team

2024-02-06

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Male or female participant aged 18 years or older
• Pathologic diagnosis of DLBCL or MCL (For Italy Sites Only: MCL patients are excluded.)
• Participants with DLBCL must have relapsed or refractory disease and have failed or been intolerant to available standard therapy
• Participants with MCL must have relapsed or refractory disease and have received at least one prior line of therapy (For Italy Sites Only: This exclusion criterion is not applicable)
• Participants who have received previous CD19-directed therapy must have a biopsy which shows CD19 expression after completion of the CD19-directed therapy
• Measurable disease as defined by the 2014 Lugano Classification
• Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block (or minimum 10 freshly cut unstained slides if block is not available)
• ECOG performance status 0 to 2
• Screening laboratory values within the following parameters:
• Absolute neutrophil count (ANC) ≥1.0 × 103/µL (off growth factors at least 72 hours)
• Platelet count ≥75 × 103/µL without transfusion in the past 7 days
• Hemoglobin ≥8 g/dL (4.96 mmol/L), transfusion allowed
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) ≤2.5 × the ULN
• Total bilirubin ≤1.5 × ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 × ULN)
• Blood creatinine ≤1.5 × ULN or calculated creatinine clearance ≥60 mL/min by the Cockcroft and Gault equation
• Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior to start of study drugs on C1D1 for women of childbearing potential
• Women of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 9 months after the last dose of loncastuximab tesirine or 1 month after last dose of ibrutinib, whichever comes last. Men with female partners who are of childbearing potential must agree that they will use a highly effective method of contraception from the time of giving informed consent until at least 6 months after the participant receives his last dose of loncastuximab tesirine or 3 months after last dose of ibrutinib, whichever comes last

You may not qualify if…

• Known history of hypersensitivity to or positive serum human anti-drug antibody (ADA) to a CD19 antibody
• Known history of hypersensitivity to ibrutinib
• Previous therapy with ibrutinib or other BTK inhibitors
• Previous therapy with loncastuximab tesirine
• Requires treatment or prophylaxis with a moderate or strong cytochrome P450 (CYP) 3A inhibitor
• Allogenic or autologous transplant within 60 days prior to start of study drugs (C1D1)
• Active graft-versus-host disease
• Post-transplantation lymphoproliferative disorder
• Active autoimmune disease, including motor neuropathy considered of autoimmune origin and other central nervous system (CNS) autoimmune disease
• Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV) virus, hepatitis B virus (HBV), or hepatitis C virus (HCV).
• History of Stevens-Johnson syndrome or toxic epidermal necrolysis
• Lymphoma with active CNS involvement at the time of screening, including leptomeningeal disease
• Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath)
• Breastfeeding or pregnant
• Significant medical comorbidities, including but not limited to, uncontrolled hypertension (blood pressure [BP] ≥160/100 millimeters of mercury (mmHg) repeatedly), unstable angina, congestive heart failure (greater than New York Heart Association class II), electrocardiographic evidence of acute ischemia, coronary angioplasty or myocardial infarction within 6 months prior to screening, uncontrolled atrial or ventricular cardiac arrhythmia, poorly controlled diabetes mellitus, or severe chronic pulmonary disease, or tuberculosis infection (tuberculosis screening based on local standards).
• Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy within 14 days prior to start of study drugs (C1D1), except shorter if approved by the Sponsor
• Use of any other experimental medication within 14 days prior to start of study drugs (C1D1)
• Planned live vaccine administration after starting study drugs (C1D1)
• Any condition that could interfere with the absorption or metabolism of ibrutinib including malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel
• Inherited or acquired bleeding disorders
• Ongoing anticoagulation treatment, except for low-dose heparinisation or equivalent
• Failure to recover to Grade ≤1 (Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) from acute non-hematologic toxicity (Grade ≤2 neuropathy or alopecia) due to previous therapy prior to screening
• Congenital long QT syndrome or a corrected QTcF interval of >480 ms at screening (unless secondary to pacemaker or bundle branch block)
• Active second primary malignancy other than non-melanoma skin cancers, non metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the Sponsor's medical monitor and Investigator agree, and document should not be exclusionary
• Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgement, make the participant inappropriate for study participation or put the participant at risk

Where it is running

• University of California Irvine Health Chao Family Comprehensive Cancer Center — Orange, California, United States
• Redlands Community Hospital — Redlands, California, United States
• University of Miami — Miami, Florida, United States
• Miami Cancer Institute — Miami, Florida, United States
• The Blood and Marrow Transplant Group of Georgia — Atlanta, Georgia, United States
• Georgia Cancer Center at Augusta University — Augusta, Georgia, United States
• Norton Cancer Institute, St. Matthews Campus — Louisville, Kentucky, United States
• The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins — Baltimore, Maryland, United States
• University of Michigan Comprehensive Cancer Center — Ann Arbor, Michigan, United States
• University of Minnesota — Minneapolis, Minnesota, United States
• Saint Vincent Healthcare — Billings, Montana, United States
• Case Western Reserve University — Cleveland, Ohio, United States
• GasthuisZusters Antwerpen Sint-Augustinus — Wilrijk, Belgium
• CHU UCL Namur (Site Godinne) — Yvoir, Belgium
• Centre Hospitalier Universitaire de Rennes Hôpital Pontchailou — Bretagne, France
• Hôpital Hôtel-Dieu — Loiré, France
• Hôpital Saint-Eloi — Montpellier, France
• Hôpital Saint-Louis — Paris, France
• Centre Hospitalier Lyon Sud — Pierre-Bénite, France
• Centre Hospitalier Universitaire De Poitier - Hopital De La Miletrie - Hopital Jean Bernard — Poitiers, France
• IRCCS istituto Clinico Humanitas U.O. di Oncologia ed Ematologia — Via Manzoni, Rozzano, Italy
• Azienda Ospedaliera Pap Giovanni XXIII — Bergamo, Italy
• Policlinico Sant'Orsola Malpighi — Bologna, Italy
• Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia — Brescia, Italy
• Istituto Scientifico Rmagnolo per lo Studio e la Cura dei Tumori — Meldola FC, Italy

Full record on ClinicalTrials.gov

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