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

NCT05222438 | Withdrawn Phase 2 FDA Drug

• 2 other identifiers: 2021-047ADCT-402-001
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Relapsed Diffuse Large B-cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (1)

Loncastuximab tesirine

EXPERIMENTAL

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

Interventions

loncastuximab tesirine DRUG

loncastuximab tesirine for maintenance therapy between day 30 and 60 following autoSCT and will receive a total of 6 months of therapy (8 cycles).

Loncastuximab tesirine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form (ICF)
• Age \>18 years
• 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
• Eligible to undergo autologous stem cell transplantation as per local investigator assessment
• 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.

You may not qualify if:

• Contraindications to any of the individual components of autoSCT or loncastuximab tesirine.
• Prior exposure to loncastuximab tesirine
• Clinically significant effusion i.e. ascites, pleural or pericardial effusion requiring drainage or associated with shortness of breath
• Patients with ongoing toxicities of grade \>1 from previous treatments except alopecia
• 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)
• Patients who are receiving any other investigational agents
• Grade 3b follicular lymphoma
• Burkitt's lymphoma
• Patients with known brain, spinal, or CSF involvement
• Systemic steroids (prednisone \>20 mg/day or equivalent) and/or immunosuppressive medications
• 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

Sponsors & Collaborators

• Barbara Ann Karmanos Cancer Institute: lead

Study Sites (1)

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

loncastuximab tesirine

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Dipenkumar Modi, M.D.

  Barbara Ann Karmanos Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 10, 2022
• First Posted: February 3, 2022
• Study Start: April 8, 2022
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: November 1, 2023

Record last verified: 2023-10

Locations

US (1)