Trial of Loncastuximab Tesirine in High Risk Diffuse Large B-cell Lymphoma Post Transplant

Phase II Trial Evaluating Safety and Efficacy of Loncastuximab Tesirine as a Maintenance Therapy Following Autologous Stem Cell Transplantation in High Risk Diffuse Large B-cell Lymphoma

Study of loncastuximab tesirine administered intravenously (IV) for maintenance therapy following autologous stem cell transplant in patients with relapsed diffuse large B cell lymphoma

Study Overview

• Status: Withdrawn
• Conditions: Relapsed Diffuse Large B-cell Lymphoma
• Intervention / Treatment: Drug: loncastuximab tesirine

Detailed Description

This is a Phase II, multicenter, open label study of loncastuximab tesirine for maintenance therapy following autologous stem cell transplant (autoSCT) in patients with relapsed diffuse large B cell lymphoma (DLBCL). Patients with relapsed DLBCL confirmed through core biopsy and meeting eligibility criteria will be enrolled in the study. Patients can be enrolled up to 4 weeks prior to autoSCT. Patients will start loncastuximab tesirine between day 30 and 60 after autoSCT as determined by the treating physician. Since majority of the relapses occur early after autoSCT, offering maintenance therapy for a finite duration might be of therapeutic benefit without posing excessive toxicity. Loncastuximab tesirine will be administered intravenously (IV) at every 3 weeks (Q3W) for a total of 6 months (8 cycles).

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed informed consent form (ICF)
2. Age >18 years

3. Patients with relapsed refractory DLBCL with any of the following high-risk features for progression following autoSCT will be enrolled:

   • Primary refractory lymphoma (failure to achieve complete remission as determined by the treating physician) following 1st line anthracycline containing chemotherapy
   • Early relapsed lymphoma with an initial remission duration of less than 12 months following 1st line anthracycline containing chemotherapy
   • Failure to achieve complete remission following salvage chemotherapy and positive PET-CT as defined by Lugano criteria (Deauville score of 4 or 5) prior to autoSCT
   • Double hit lymphoma (DHL) or triple hit lymphoma (THL) confirmed by FISH testing by local pathology (defined as high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements)
   • Double expressor lymphoma (DEL) as confirmed by immunohistochemistry (IHC) by local pathology (MYC and BCL2 or BCL6 positivity)
   • CMYC rearranged (by FISH) DLBCL
   • High IPI score (≥3 points)
   • Stage 3-4 disease at diagnosis
   • Extra-lymphatic disease
   • High grade B cell lymphoma
4. Eligible to undergo autologous stem cell transplantation as per local investigator assessment
5. Availability of biopsy specimens confirming DLBCL relapse. Archival formalin-fixed paraffin-embedded (FFPE) tissue blocks or 15 unstained slides serial sections (5-10 μm in thickness) must be available prior to study enrollment. The pathology report must be available. IHC testing of CMYC, BCL2, and BCL6 expression, and FISH testing of CMYC, BCL2 and BCL6 gene rearrangement must be available prior to enrollment. CD19 expression status must be available prior to enrollment.
6. Patients previously treated with CD19-targeted therapy (including CAR T) must have a subsequent biopsy and/or flow cytometry confirming CD19 positivity.
7. ECOG Performance Status of 0, 1, or 2
8. Life expectancy of at least 6 months
9. Ability and willingness to comply with the study protocol procedures
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 9 months 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 6 months after the patient receives his last dose of loncastuximab tesirine

Exclusion Criteria:

1. Contraindications to any of the individual components of autoSCT or loncastuximab tesirine.
2. Prior exposure to loncastuximab tesirine
3. Clinically significant effusion i.e. ascites, pleural or pericardial effusion requiring drainage or associated with shortness of breath
4. Patients with ongoing toxicities of grade >1 from previous treatments except alopecia
5. Patients with clinically significant history of liver disease including cirrhosis or hepatitis (viral hepatitis). However, treated viral hepatitis may be allowed Patients with history of severe skin disorders including Steven-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN)
6. Patients who are receiving any other investigational agents
7. Grade 3b follicular lymphoma
8. Burkitt's lymphoma
9. Patients with known brain, spinal, or CSF involvement
10. Systemic steroids (prednisone >20 mg/day or equivalent) and/or immunosuppressive medications

11. Unstable cardiovascular function that could affect compliance with the protocol:

    • Symptomatic ischemia, or
    • Congestive heart failure (CHF) of NYHA Class ≥3, or
    • Myocardial infarction (MI) within 3 months
    • Left ventricular ejection fraction <45% based on echocardiogram or MUGA scan obtained within 6 months prior to enrollment
    • History or presence of an abnormal ECG that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third-degree heart block.

12. Positive test results for chronic hepatitis B virus (HBV) infection (defined as positive hepatitis B surface antigen [HBsAg]):

    -Patients with occult or prior HBV infection (defined as negative HBsAg and positive hepatitis B core antibody [HBcAb]) may be included if HBV DNA PCR is undetectable, provided that they are willing to undergo DNA testing on Day 1 of every cycle of study treatment. Patients who have protective titers of hepatitis B surface antibody (HBsAb) after vaccination or prior but cured hepatitis B are eligible.

13. Known history of HIV seropositive status
14. Patients with a history of progressive multifocal leukoencephalopathy

15. Any of the following, unless abnormal laboratory values are due to underlying lymphoma per the investigator:

    • Creatinine > 1.5 x ULN or a measured creatinine clearance < 40 mL/min
    • AST or ALT > 2.5 x ULN
    • Total bilirubin > 1.5 x ULN. Patients with documented Gilbert disease may be enrolled if total bilirubin is < 3 x ULN
    • INR or PT > 1.5 x ULN in the absence of therapeutic anticoagulation
    • PTT or aPTT > 1.5 x ULN in the absence of a lupus anticoagulant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Loncastuximab tesirine; Patients will start loncastuximab tesirine for maintenance therapy between day 30 and 60 following autoSCT and will receive a total of 6 months of therapy (8 cycles). Patients will receive IV infusion of loncastuximab tesirine 150 μg/kg at Q3W for the first 2 cycles followed by 75 μg/kg at Q3W for the remaining 6 cycles.	Drug: loncastuximab tesirine; loncastuximab tesirine for maintenance therapy between day 30 and 60 following autoSCT and will receive a total of 6 months of therapy (8 cycles).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy Outcome Measure	Progression-free survival (PFS) assessments will be determined according to Lugano Response Criteria. The distributions of time to event data will be graphically summarized using Kaplan-Meier (KM) curves and their median and confidence intervals will be estimated using KM estimates.	From the start date of treatment initation until the date of progression or death from any cause, whichever occurs first, assessed up to 1-year following autoSCT
Safety Outcome Measure	Evaluate the safety and tolerability as defined by CTCAE 5.0 criteria	Up to 30 days after last dose of study treatment

Collaborators and Investigators

• Sponsor: Barbara Ann Karmanos Cancer Institute
• Investigators: Principal Investigator: Dipenkumar Modi, M.D., Barbara Ann Karmanos Cancer Institute

Study record dates

Study Major Dates

• Study Start (Estimated): April 8, 2022
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: January 10, 2022
• First Submitted That Met QC Criteria: January 24, 2022
• First Posted (Actual): February 3, 2022

Study Record Updates

• Last Update Posted (Actual): November 1, 2023
• Last Update Submitted That Met QC Criteria: October 30, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Antineoplastic Agents; Antineoplastic Agents, Immunological; Loncastuximab tesirine
• Other Study ID Numbers: 2021-047; ADCT-402-001 (Other Identifier: ADC Therapeutics)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes