A Phase 3 Randomized Study of Loncastuximab Tesirine Combined with Rituximab Versus Immunochemotherapy in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (LOTIS-5)
- Conditions
- 10025320non-Hodgkin Lymphoma
- Registration Number
- NL-OMON53841
- Lead Sponsor
- ADC Therapeutics SA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 10
1. Male or female patient aged 18 years or older
2. Pathologic diagnosis of DLBCL, as defined by the 2016 World Health
Organization classification (including patients with DLBCL transformed from
indolent lymphoma), or high-grade B cell lymphoma, with MYC and BCL2 and/or
BCL6 rearrangements
3. Relapsed (disease that has recurred following a response) or refractory
(disease that failed to respond to prior therapy) disease following at least
one multi-agent systemic treatment regimen
4. Not considered by the investigator to be a candidate for stem cell
transplantation based on performance status, advanced age, and/or significant
medical comorbidities such as organ dysfunction
5. Measurable disease as defined by the 2014 Lugano Classification as assessed
by positron-emission tomography (PET) - computed tomography (CT) or by CT or
magnetic resonance imaging (MRI) if tumor is not fluorodeoxyglucose (FDG)-avid
on screening PET-CT
6. 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.
7. ECOG performance status 0-2
8. Adequate organ function as defined by screening laboratory values within the
following parameters:
a. Absolute neutrophil count >=1000/µL (off growth factors at least 72 hours)
b. Platelet count >=100000/µL without transfusion within the past 2 weeks
c. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and
gamma glutamyl transferase (GGT) <=2.5 × the upper limit of normal (ULN)
d. Total bilirubin <=1.5 × ULN (patients with known Gilbert*s syndrome may
have a total bilirubin up to <=3 × ULN)
e. Calculated creatinine clearance >=30 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.
9. Negative beta-human chorionic gonadotropin (β-hCG) pregnancy test within 7
days prior to start of study drug (Cycle 1 Day 1) 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 12
months after the last dose of study treatment. Men with female partners who are
of childbearing potential must agree to use a condom when sexually active or
practice total abstinence from the time of giving informed consent until at
least 7 months after the patient receives his last dose of study treatment.
1. Previous treatment with loncastuximab tesirine
2. Previous treatment with R-GemOx
3. Known history of hypersensitivity to a CD19 antibody, loncastuximab tesirine
(including SG3249) or any of its excipients, or history of or positive serum
human ADA or positive serum human ADA to a CD19 antibody
4. Pathologic diagnosis of Burkitt lymphoma
5. 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
6. Autologous transplant within 30 days prior to start of study drug (Cycle 1
Day 1)
7. Allogeneic transplant within 60 days prior to start of study drug (Cycle 1
Day 1)
8. Active graft-versus-host disease
9. Post-transplantation lymphoproliferative disorders
10. Active autoimmune disease, including motor neuropathy considered of
autoimmune origin and other central nervous system (CNS) autoimmune disease
11. Human immunodeficiency virus (HIV) seropositive with any of the following:
a. CD4+ T-cell (CD4+) counts <350 cells/µL
b. Acquired immunodeficiency syndrome-defining opportunistic infection within
12 months prior to screening
c. Not on anti-retroviral therapy, or on anti-retroviral therapy for <4 weeks
at the time of screening
d. HIV viral load >=400 copies/mL
12. Serologic evidence of chronic hepatitis B virus (HBV) infection and unable
or unwilling to receive standard prophylactic antiviral therapy or with
detectable HBV viral load
13. Serologic evidence of hepatitis C virus (HCV) infection without completion
of curative treatment or with detectable HCV viral load
14. History of Stevens-Johnson syndrome or toxic epidermal necrolysis
15. Lymphoma with active CNS involvement, including leptomeningeal disease
16. 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)
17. Breastfeeding or pregnant
18. Uncontrolled hypertension (blood pressure >=160/100 mm Hg 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, severe chronic pulmonary disease, or other serious medical
condition which is likely to significantly impair the patient*s ability to
tolerate the study treatment
19. Major surgery within 4 weeks prior to start of study drug (Cycle 1 Day 1);
radiotherapy, chemotherapy or other antineoplastic therapy within 14 days prior
to start of study drug (Cycle 1 Day 1), except shorter if approved by the
Sponsor
20. Use of any other experimental medication within 14 days or 5 half-lives
prior to start of study drug (Cycle 1 Day 1)
21. Received live vaccine within 4 weeks of Cycle 1 Day 1
22. Failure to recover to <=Grade 1 (Common Terminology Criteria for Adverse
Events [CTCAE] version 5.0) from acute non hematologic toxicity (except
alopecia) due to previous therapy prior to screening
23. Congenital long QT
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Progression-free survival (PFS) defined as the time between randomization and<br /><br>the first documentation of recurrence or progression by independent central<br /><br>review, or death from any cause</p><br>
- Secondary Outcome Measures
Name Time Method