oncastuximab tesirine administered as a consolidation treatment after immunochemotherapy in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL)

Phase 1

• Conditions: Bruton Tyrosine Kinase inhibitors (BTKi) treated (or BTKi intolerant) relapsed/refractory (R/R) Mantle Cell Lymphoma (MCL).; MedDRA version: 21.0Level: PTClassification code 10026800Term: Mantle cell lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2021-000715-23-IT
• Lead Sponsor: FONDAZIONE ITALIANA LINFOMI ONLUS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-10-04
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

1) Histologically documented diagnosis of MCL as defined in the 2017 edition of the World Health Organization (WHO) classification;
2) Age >= 18 and < 80 years;
3) Relapsed/Refractory disease after one, two or three lines of treatment;
4) Bendamustine-naive or relapsed after at least two years after the last cycle of a bendamustine-containing regimen;
5) Previous treatment with BTKi monotherapy or BTKi containing regimens with R/R disease; and/or patients who discontinued BTKi monotherapy or BTKi containing regimens for adverse events and have active disease necessitating treatment;
6) Venetoclax treated patients are allowed;
7) Stem cell transplant eligible patients are allowed;
8) Measurable nodal or extranodal disease >= 1.5 cm in longest diameter, and measurable in 2 perpendicular dimensions.
9) ECOG/WHO performance status <= 2 (unless MCL-related);
10) Adequate liver, renal and bone marrow function, assessed by baseline laboratory values as indicated in the protocol;
11) Subject understands and voluntarily signs an informed consent form approved by an Independent Ethics Committee (IEC), prior to the initiation of any screening or study-specific procedures;
12) Subject must be able to adhere to the study visit schedule and other protocol requirements;
13) Life expectancy >= 3 months;
14) Women of childbearing potential (WOCBP) and men must agree to use effective contraception if sexually active. This applies for the time period between signing of the informed consent form and at least 16 weeks after last loncastuximab tesirine (ADCT-402) dose.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 22
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 34

Exclusion Criteria

1) Subjects who have received a bendamustine containing regimen and relapsed less than two years after the end of treatment;
2) Known history of hypersensitivity to human antibodies;
3) Allogenic stem cell transplant within 6 months prior to start of first study drug;
4) Allogenic stem cell transplant with active / uncontrolled graft-versus-host disease;
5) Previous treatment with CD19 targeting agents;
6) More than three lines of previous treatment (autologous stem cell transplant performed as part of consolidation to a previous line of therapy should not be considered as a line of therapy);
7) Active second malignancy in the last three years other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or any other tumor that the Sponsor and Coordinating Investigator agree and document should not be considered preclusive to participate in the study;
8) Major surgery or any anticancer therapy including chemotherapy, immunotherapy, radiotherapy, investigational therapy, including targeted small molecule agents within 14 days prior to start of study drug (R-BAC).
9) Cardiovascular disease (NYHA class =2);
10) Significant history of neurologic, psychiatric, endocrinological, metabolic, immunologic, or hepatic disease that would preclude participation in the study or compromise ability to give informed consent;
11) Evidence of other clinically significant uncontrolled condition(s) as specified in protocol;

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of a consolidation with loncastuximab tesirine following salvage immunochemotherapy (2 courses of Rituximab-Bendamustine-Cytarabine, R-BAC) in Bruton Tyrosine Kinase inhibitors (BTKi) treated (or BTKi intolerant) relapsed/refractory (R/R) Mantle Cell Lymphomas (MCL).;Secondary Objective: - To evaluate the safety profile of loncastuximab tesirine consolidation.<br>- To assess the rate of Minimal Residual Disease (MRD) negativity after loncastuximab tesirine consolidation.;Primary end point(s): 12-month Progression-Free Survival (PFS). PFS will be assessed on an ITT (Intention to Treat) basis.;Timepoint(s) of evaluation of this end point: Time between the date of enrollment and the first documentation of recurrence, progression or death from any cause. Responding patients and patients who are lost to follow up will be censored at their last assessment date.