A Phase 2 Study of Loncastuximab Tesirine in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
- Conditions
- Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)MedDRA version: 20.0Level: 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
- EUCTR2017-004288-11-IT
- Lead Sponsor
- ADC THERAPEUTICS SA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 140
1. Male or female patient aged 18 years or older
2. Pathologic diagnosis of DLBCL, as defined by the 2016 WHO classification, to include: DLBCL not otherwise specified; primary mediastinal large B-cell lymphoma; and high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
3. Relapsed or refractory disease following two or more multi-agent systemic treatment regimens
4. Patients who have received previous CD19-directed therapy must have a biopsy that shows CD19 protein expression after completion of the CD19-directed therapy
5. Measurable disease as defined by the 2014 Lugano Classification
6. Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block (or minimum 10 freshly cut unstained slides if block is not available)
7. ECOG performance status 0-2
8. Adequate organ function as defined by 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 prior 7 days
c. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) =2.5 × the upper limit of normal (ULN); =5 × ULN if there is liver involvement
d. Total bilirubin =1.5 × ULN (patients with known Gilbert’s syndrome may have a total bilirubin up to =3 × ULN)
e. Blood creatinine =1.5 × ULN or calculated creatinine clearance =60 mL/min by the Cockcroft and Gault equation
9. Negative beta-human chorionic gonadotropin (ß-HCG) pregnancy test within 7 days prior to start of study drug (C1D1) for women of childbearing potential
10. 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 loncastuximab tesirine. 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 16 weeks after the patient receives his last dose of loncastuximab tesirine
Are the trial subjects under 18? no
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 42
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 98
1. Previous treatment with loncastuximab tesirine
2. Known history of hypersensitivity to or positive serum human ADA to a CD19 antibody
3. Pathologic diagnosis of Burkitt lymphoma
4. 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
5. Autologous stem cell transplant within 30 days prior to start of study drug (C1D1)
6. Allogeneic stem cell transplant within 60 days prior to start of study drug (C1D1)
7. Active graft-versus-host disease
8. Post-transplant lymphoproliferative disorders
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 virus (HIV), 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, or severe chronic pulmonary disease
16. Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy within 14 days prior to start of study drug (C1D1), except shorter if approved by the Sponsor
17. Use of any other experimental medication within 14 days prior to start of study drug (C1D1)
18. Planned live vaccine administration after starting study drug (C1D1)
19. 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
20. Congenital long QT syndrome or a corrected QTcF interval of >480 ms at screening (unless secondary to pacemaker or bundle branch block)
21. 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 Main Objective: Evaluate the efficacy of single agent loncastuximab tesirine in patients with relapsed or refractory DLBCL;Secondary Objective: Characterize the safety profile of loncastuximab tesirine<br>Characterize the pharmacokinetic (PK) profile of loncastuximab tesirine<br>Evaluate the immunogenicity of loncastuximab tesirine<br>Evaluate the impact of loncastuximab tesirine treatment on health-related quality of life (HRQoL)<br>;Primary end point(s): ORR according to the 2014 Lugano classification as determined by central review in all treated patients; ORR is defined as the proportion of patients with a best overall response (BOR) of CR or PR;Timepoint(s) of evaluation of this end point: Primary end point evaluated at 6 and 12 weeks after first dose, then every 9 weeks until disease progression.
- Secondary Outcome Measures
Name Time Method