Clinical Trials /

Study to Evaluate Loncastuximab Tesirine With Rituximab Versus Immunochemotherapy in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

NCT04384484

Description:

The purpose of this study is to evaluate the efficacy of loncastuximab tesirine (ADCT-402) combined with rituximab compared to standard immunochemotherapy.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • High Grade B-Cell Lymphoma with MYC and BCL2 and/or BCL6 Rearrangements
  • Transformed Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study to Evaluate Loncastuximab Tesirine With Rituximab Versus Immunochemotherapy in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: ADCT-402-311
  • SECONDARY ID: 2020-000241-14
  • NCT ID: NCT04384484

Conditions

  • Relapsed Diffuse Large B-Cell Lymphoma
  • Refractory Diffuse Large B-Cell Lymphoma

Interventions

DrugSynonymsArms
Loncastuximab TesirineADCT-402Part 1: Loncastuximab Tesirine + Rituximab (Lonca-R)
RituximabPart 1: Loncastuximab Tesirine + Rituximab (Lonca-R)
GemcitabinePart 2: Standard Immunochemotherapy (R-GemOx)
OxaliplatinPart 2: Standard Immunochemotherapy (R-GemOx)

Purpose

The purpose of this study is to evaluate the efficacy of loncastuximab tesirine (ADCT-402) combined with rituximab compared to standard immunochemotherapy.

Trial Arms

NameTypeDescriptionInterventions
Part 1: Loncastuximab Tesirine + Rituximab (Lonca-R)ExperimentalPart 1 consists of a non-randomized safety run-in period evaluating the study drug for the first 20 participants. Participants will receive Lonca-R on Day 1 of each cycle for up to 8 cycles, where 1 cycle is 3 weeks. Lonca-R will be administered via an intravenous infusion of loncastuximab tesirine 150 µg/kg + rituximab 375 mg/m^2 every 3 weeks (Q3W) for 2 cycles, then loncastuximab tesirine 75 µg/kg + rituximab 375 mg/m^2 Q3W for up to 6 additional cycles.
  • Loncastuximab Tesirine
  • Rituximab
Part 2: Loncastuximab Tesirine + Rituximab (Lonca-R)ExperimentalRandomized participants will receive Lonca-R on Day 1 of each cycle for up to 8 cycles, where 1 cycle is 3 weeks. Lonca-R will be administered via an intravenous infusion of loncastuximab tesirine 150 µg/kg + rituximab 375 mg/m^2 every 3 weeks (Q3W) for 2 cycles, then loncastuximab tesirine 75 µg/kg + rituximab 375 mg/m^2 Q3W for up to 6 additional cycles.
  • Loncastuximab Tesirine
  • Rituximab
Part 2: Standard Immunochemotherapy (R-GemOx)Active ComparatorRandomized participants will receive R-GemOx consisting of rituximab, gemcitabine and oxaliplatin as a standard immunochemotherapy treatment on Day 1 of each cycle for up to 8 cycles, where 1 Cycle is 2 weeks. R-GemOx will be administered via an intravenous infusion of rituximab 375 mg/m^2 + gemcitabine 1000 mg/m^2 + oxaliplatin 100 mg/m^2 every 2 weeks (Q2W) for up to 8 cycles.
  • Rituximab
  • Gemcitabine
  • Oxaliplatin

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female participant aged 18 years or older

          -  Pathologic diagnosis of DLBCL, as defined by the 2016 World Health Organization
             classification (including participants with DLBCL transformed from indolent lymphoma),
             or high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements

          -  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

          -  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

          -  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 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

          -  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

          -  ECOG performance status 0-2

          -  Adequate organ function as defined by screening laboratory values within the following
             parameters:

               1. Absolute neutrophil count ≥1.0 × 10^3/μL (off growth factors for at least 72
                  hours)

               2. Platelet count ≥75 × 10^3/μL without transfusion within the past 2 weeks

               3. ALT, AST, and GGT ≤2.5 × the upper limit of normal (ULN)

               4. Total bilirubin ≤1.5 × ULN (participants with known Gilbert's syndrome may have a
                  total bilirubin up to ≤3 × ULN)

               5. 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.

          -  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

          -  Women of childbearing potential (WOCBP) 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 20 weeks after
             the participant receives his last dose of loncastuximab tesirine.

        Exclusion Criteria:

          -  Previous treatment with loncastuximab tesirine

          -  Previous treatment with R-GemOx

          -  Known history of hypersensitivity to or positive serum human ADA to a CD19 antibody

          -  Pathologic diagnosis of Burkitt lymphoma

          -  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

          -  Autologous transplant within 30 days prior to start of study drug (Cycle 1 Day 1)

          -  Allogeneic transplant within 60 days prior to start of study drug (Cycle 1 Day 1)

          -  Active graft-versus-host disease

          -  Post-transplantation lymphoproliferative disorders

          -  Active autoimmune disease, including motor neuropathy considered of autoimmune origin
             and other central nervous system (CNS) autoimmune disease

          -  Human immunodeficiency virus (HIV) seropositive with any of the following:

               1. CD4+ T-cell (CD4+) counts <350 cells/μL

               2. Acquired immunodeficiency syndrome-defining opportunistic infection within 12
                  months prior to screening

               3. Not on anti-retroviral therapy, or on anti-retroviral therapy for <4 weeks at the
                  time of screening

               4. HIV viral load ≥400 copies/mL

          -  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

          -  Serologic evidence of hepatitis C virus (HCV) infection without completion of curative
             treatment or with detectable HCV viral load

          -  History of Stevens-Johnson syndrome or toxic epidermal necrolysis

          -  Lymphoma with active CNS involvement, 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

          -  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
             participant's ability to tolerate the study treatment

          -  Major surgery, 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

          -  Use of any other experimental medication within 14 days or 5 half-lives prior to start
             of study drug (Cycle 1 Day 1)

          -  Received live vaccine within 4 weeks of Cycle 1 Day 1

          -  Failure to recover to ≤Grade 1 (Common Terminology Criteria for Adverse Events [CTCAE]
             version 5.0) from acute non-hematologic toxicity (except ≤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)

          -  Any other significant medical illness, abnormality, or condition that would, in the
             Investigator's judgment, make the participant inappropriate for study participation or
             put the participant at risk
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free Survival (PFS)
Time Frame:Up to 4 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:Up to 4 years
Safety Issue:
Description:
Measure:Overall Response Rate (ORR)
Time Frame:Up to 4 years
Safety Issue:
Description:
Measure:Complete Response Rate (CRR)
Time Frame:Up to 4 years
Safety Issue:
Description:
Measure:Duration of Response (DOR)
Time Frame:Up to 4 years
Safety Issue:
Description:
Measure:Number of Participants Who Experience At Least One Treatment-Emergent Adverse Event (TEAE)
Time Frame:Day 1 up to a maximum of Week 25
Safety Issue:
Description:
Measure:Number of Participants Who Experience At Least One Serious Adverse Event (SAE)
Time Frame:Up to 4 years
Safety Issue:
Description:
Measure:Number of Participants Who Experience a Clinically Significant Change From Baseline in Clinical Laboratory Results
Time Frame:Day 1 up to a maximum of Week 25
Safety Issue:
Description:
Measure:Number of Participants Who Experience a Clinically Significant Change From Baseline in Vital Sign Measurements
Time Frame:Day 1 up to a maximum of Week 25
Safety Issue:
Description:
Measure:Number of Participants Who Experience a Clinically Significant Change From Baseline in Physical Examinations
Time Frame:Day 1 up to a maximum of Week 25
Safety Issue:
Description:
Measure:Number of Participants Who Experience a Clinically Significant Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status
Time Frame:Day 1 up to a maximum of Week 25
Safety Issue:
Description:
Measure:Number of Participants Who Experience a Clinically Significant Change From Baseline in Electrocardiogram (ECG) Results
Time Frame:Day 1 up to a maximum of Week 25
Safety Issue:
Description:
Measure:Average Concentration of Loncastuximab Tesirine at the End of Infusion
Time Frame:Day 1 of Cycles 1 through 6 (each cycle is 3 weeks)
Safety Issue:
Description:
Measure:Average Concentration of Loncastuximab Tesirine Before Infusion
Time Frame:Day 1 of Cycles 2 through 6 (each cycle is 3 weeks)
Safety Issue:
Description:
Measure:Number of Participants With Anti-Drug Antibody (ADA) Titers to Loncastuximab Tesirine
Time Frame:Day 1 up to a maximum of Week 25
Safety Issue:
Description:
Measure:Part 2: Change from Baseline in Health-Related Quality of Life (HRQoL) as Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire -Core 30 (EORTC QLQ-C30)
Time Frame:Baseline up to a maximum of Week 25
Safety Issue:
Description:
Measure:Part 2: Change from Baseline in Health-Related Quality of Life (HRQoL) as Measured by the Lymphoma Subscale of Functional Assessment of Cancer Therapy- Lymphoma (LymS of FACT-Lym)
Time Frame:Baseline up to a maximum of Week 25
Safety Issue:
Description:
Measure:Part 2: Change from Baseline in Health-Related Quality of Life (HRQoL) as Measured by GP5 Item of the Functional Assessment of Cancer Therapy- Lymphoma (FACT-Lym)
Time Frame:Baseline up to a maximum of Week 25
Safety Issue:
Description:
Measure:Part 2: Change from Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)
Time Frame:Baseline to up to 4 years
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:ADC Therapeutics S.A.

Trial Keywords

  • Loncastuximab Tesirine
  • Refractory Diffuse Large B-Cell Lymphoma
  • Relapsed Diffuse Large B-Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Lymphoma

Last Updated

September 25, 2020