study to assess how safe and how effective is Loncastuximab Tesirine together with Ibrutinib in patients with Advanced Diffuse Large B Cell Lymphoma or Mantle Cell Lymphoma
- Conditions
- Diffuse large B-Cell lymphoma (DLBCL) or mantle cell lymphoma (MCL)MedDRA version: 20.0Level: PTClassification code 10061275Term: Mantle cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: PTClassification code 10012818Term: Diffuse large B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-002625-38-BE
- Lead Sponsor
- ADC Therapeutics SA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 161
1.Male or female patient aged 18 years or older
2.Pathologic diagnosis of DLBCL or MCL
3.Patients with DLBCL must have relapsed or refractory disease and have failed or been intolerant to available standard therapy
4.Patients with MCL must have relapsed or refractory disease and have received at least one prior line of therapy
5.Patients who have received previous CD19-directed therapy must have a biopsy which shows CD19 expression after completion of the CD19-directed therapy
6.Measurable disease as defined by the 2014 Lugano Classification
7.Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block (or minimum 10 freshly cut unstained slides if block is not available)
Note: Any biopsy since initial diagnosis is acceptable, but if several samples are available, the most recent sample is preferred.
8.ECOG performance status 0 to 2
9.Screening laboratory values within the following parameters:
a.Absolute neutrophil count (ANC) =1.0 × 10^3/µL (off growth factors at least 72 hours)
b.Platelet count =75 × 10^3/µL without transfusion in the past 7 days
c.Hemoglobin =8 g/dL (4.96 mmol/L), transfusion allowed
d.Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) =2.5 × the upper limit of normal (ULN)
e.Total bilirubin =1.5 × ULN (patients with known Gilbert’s syndrome may have a total bilirubin up to =3 × ULN)
f.Blood creatinine =1.5 × ULN or calculated creatinine clearance =60 mL/min by the Cockcroft and Gault equation
Note: A laboratory assessment may be repeated a maximum of two times during the Screening period to confirm eligibility.
10.Negative beta-human chorionic gonadotropin (ß-HCG) pregnancy test within 7 days prior to start of study drugs on C1D1 (cycle 1 day 1) for women of childbearing potential
11.Women of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 16 weeks after the last dose of study therapy. 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 20 weeks after the patient receives his last dose of study therapy
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 113
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 48
1.Known history of hypersensitivity to or positive serum human ADA to a CD19 antibody
2.Known history of hypersensitivity to ibrutinib
3.Previous therapy with ibrutinib or other BTK inhibitors
4.Previous therapy with loncastuximab tesirine
5.Requires treatment or prophylaxis with a moderate or strong cytochrome P450 (CYP) 3A inhibitor
6.Allogenic or autologous transplant within 60 days prior to start of study drugs (C1D1)
7.Active graft-versus-host disease
8.Post-transplantation lymphoproliferative disorder
9.Active autoimmune disease, including motor neuropathy considered of autoimmune origin and other central nervous system (CNS) autoimmune disease
10.Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV) virus, hepatitis B virus (HBV), or hepatitis C virus (HCV).
11.History of Stevens-Johnson syndrome or toxic epidermal necrolysis
12.Lymphoma with active CNS involvement at the time of screening, including leptomeningeal disease
13.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)
14.Breastfeeding or pregnant
15.Significant medical comorbidities, including but not limited to, uncontrolled hypertension (blood pressure [BP] =160/100 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)
16.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
17.Use of any other experimental medication within 14 days prior to start of study drugs (C1D1)
18.Planned live vaccine administration after starting study drugs (C1D1)
19.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
20.Inherited or acquired bleeding disorders
21.Ongoing anticoagulation treatment, except for low dose heparinisation or equivalent
22.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
23.Congenital long QT syndrome or a corrected QTcF interval of >480 ms at screening (unless secondary to pacemaker or bundle branch block)
24.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
25.Any other significant medical illness, abnormality, or condition that would, in the Investigator’s judgment, make the patient inappropriate for study participation or put the patient at risk
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method