Consolidation With Loncastuximab Tesirine After a Short Course of Immunochemotherapy in BTKi-treated (or Intolerant) Relapsed/Refractory Mantle Cell Lymphoma Patients.

NCT05249959 | Recruiting Phase 2 DMC

• 1 other identifier: FIL_COLUMN
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 21

Brief Summary

This is a prospective, phase 2, multicenter, open-label, single-arm study. Primary objective is to assess the efficacy of loncastuximab tesirine given as consolidation therapy after salvage immunochemotherapy in BTKi (Bruton Tyrosine Kinase inhibitors) -treated (or BTKi intolerant) R/R (Relapse or Refractory) MCL (Mantle Cell Lymphoma) patients. The sponsor of this clinical trial is Fondazione Italiana Linfomi - ETS (FIL ETS).

Conditions

Relapsed Mantle Cell Lymphoma; Refractory Mantle Cell Lymphoma

Keywords

Relapsed/Refractory Mantle Cell Lymphoma (MCL); ADCT-402 (loncastuximab tesirine); BTKi (Bruton Tyrosine Kinase inhibitors) - treated; BTKi (Bruton Tyrosine Kinase inhibitors) intolerant

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  The length of time during and after the treatment that patients live with the disease, but it does not get worse. Progression-Free Survival (PFS) will be defined from 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. PFS will be assessed on an ITT (Intention to Treat) basis.

  The primary endpoint will be assessed from the beginning of the study up to 36 months.

Secondary Outcomes (8)

• Overall Survival (OS)

  The endpoint will be assessed from the beginning of the study up to 36 months

• Overall Response Rate (ORR)

  The endpoint will be assessed from the beginning of the study therapy up to 6 months

• Duration of Response (DOR)

  The endpoint will be assessed from the beginning of the study therapy up to 36 months

• Event-Free Survival (EFS)

  The endpoint will be assessed from the beginning of the study therapy up to 36 months

• MRD (Minimal Residual Disease) negativity rate

  The endpoint will be assessed from the beginning of the study therapy up to 18 months

Study Arms (1)

Consolidation with ADCT-402 (loncastuximab tesirine) after a short course of immunochemotherapy

EXPERIMENTAL

R/R MCL after one, two, three or four lines of treatment including BTKi treatment (or BTKi intolerant), with complete response (CR) or partial response (PR) or with stable disease (SD) after salvage immunochemotherapy (R-BAC, Rituximab - Bendamustine, Ara-C x 2 cycles) will undergo consolidation with loncastuximab tesirine. A patient with CR, PR or SD after one R-BAC course, which is unable to undergo a second course due to toxicity to chemotherapy, can be considered to proceed for consolidation.

Drug: Consolidation with ADCT-402 (loncastuximab tesirine) after salvage immunochemotherapy at standard dose (R-BAC, Rituximab - Bendamustine, Ara-C)); Drug: Consolidation with ADCT-402 (loncastuximab tesirine) after salvage immunochemotherapy at reduced dose (R-BAC, Rituximab - Bendamustine, Ara-C)

Interventions

Consolidation with ADCT-402 (loncastuximab tesirine) after salvage immunochemotherapy at standard dose (R-BAC, Rituximab - Bendamustine, Ara-C)) DRUG

Standard Induction phase (cycle 1-2 of R-BAC every 28 days according to the following schedule): * Rituximab 375 mg/m2 i.v. Day 1 * Bendamustine 70 mg/m2, Days 2 and 3 * Cytarabine 500 mg/m2, Day 2-4 After restaging at the End of Induction (EOI) patients with CR (complete response), PR (partial response) or SD (stable disease) will receive: CONSOLIDATION PHASE: * 2 infusions of loncastuximab tesirine at a dose of 150 microgram/kg every three weeks followed by * 2 infusions of loncastuximab tesirine at a dose of 75 microgram/kg every three weeks

Consolidation with ADCT-402 (loncastuximab tesirine) after a short course of immunochemotherapy

Consolidation with ADCT-402 (loncastuximab tesirine) after salvage immunochemotherapy at reduced dose (R-BAC, Rituximab - Bendamustine, Ara-C) DRUG

Reduced Induction phase (cycle 1-2 with two different schedules for patients deemed FRAIL or UNFIT for standard induction therapy,based on protocol dose and as per medical judgment are allowed). * Rituximab 375 mg/m2 i.v. Day 1 * Bendamustine 70 mg/m2, Days 2 and 3 * Cytarabine 500 mg/m2, Day 2 and 3 or * Rituximab 375 mg/m2 i.v. Day 1 * Bendamustine 100 mg, Days 2 and 3 * Cytarabine 500 mg, Day 2 and 3 After restaging at the End of Induction (EOI) patients with CR (complete response), PR (partial response) or SD (stable disease) will receive: CONSOLIDATION PHASE: * 2 infusions of loncastuximab tesirine at a dose of 150 microgram/kg every three weeks followed by * 2 infusions of loncastuximab tesirine at a dose of 75 microgram/kg every three weeks

Consolidation with ADCT-402 (loncastuximab tesirine) after a short course of immunochemotherapy

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically documented diagnosis of MCL as defined in the 2017 edition of the World Health Organization (WHO) classification
• Age ≥ 18 and \< 85 years
• Relapsed/Refractory disease after one, two, three or four lines of treatment
• Bendamustine-naive or relapsed after at least one year after the last cycle of a bendamustine-containing regimen
• Previous treatment with BTKi (Bruton Tyrosine Kinase inhibitors) 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.
• Previous treatment with any anti-CD19 agents is allowed (included CAR-T treatment) If previous anti-CD19 treatment has occurred, tissue CD19 expression must be assessed by histology or flow cytometry
• Venetoclax treated patients are allowed.
• Stem cell transplant eligible patients are allowed.
• Measurable nodal or extranodal disease ≥ 1.5 cm in longest diameter, and measurable in 2 perpendicular dimensions. Note: Patients with bone marrow involvement only are eligible. In case of bone marrow infiltration only, bone marrow aspiration and biopsy are mandatory for all staging evaluations
• ECOG (Eastern Cooperative Oncology Group)/WHO (World Health Organization) performance status ≤ 2 (unless MCL-related)
• The following laboratory values at screening (unless due to bone marrow involvement by lymphoma):
• Absolute Neutrophil count (ANC) \> 1.0×109/L
• Platelet count ≥ 75.000/mm3
• Creatinine clearance ≥ 40 mL/min (Cockcroft-Gault formula)
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN (upper limit of normal)

You may not qualify if:

• Subjects who have received a bendamustine containing regimen and relapsed less than one year after the end of treatment.
• Known history of hypersensitivity to human antibodies.
• Allogenic stem cell transplant within 6 months prior to start of first study drug.
• Allogenic stem cell transplant with active / uncontrolled graft-versus-host disease.
• Previous treatment with CD19 targeting agents.
• More than four 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).
• 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.
• 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). A shorter interval in special settings must be approved by the Sponsor and/or Investigator.
• Cardiovascular disease (NYHA, New York Heart Association, class ≥2).
• 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.
• Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
• Uncontrolled and/or active systemic infection (viral including COVID 19, bacterial or fungal);
• Chronic or acute hepatitis B (HBV) or hepatitis C (HCV) requiring treatment. Note:
• subjects with serologic evidence of prior vaccination to HBV (i.e., HBsAg negative, HBsAb positive and HBcAb negative) or positive HBcAb from previous infection or intravenous immunoglobulins (IVIG) may participate; inactive carriers (HBsAg positive with undetectable HBV DNA) are eligible. Patients with presence of HCV antibody are eligible only if PCR results (polimerase chain reaction) negative for HCV RNA.
• HIV seropositivity.

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead

Study Sites (21)

ASST Spedali Civili di Brescia

Brescia, Italy, 25123, Italy

RECRUITING

S.C. Ematologia - A.S.O. "SS Antonio e Biagio e Cesare Arrigo"

Alessandria, Italy

RECRUITING

S.C. di Ematologia - A.O. S. Croce e Carle

Cuneo, 12100, Italy

RECRUITING

Unità funzionale di Ematologia - Azienda Ospedaliera Universitaria Careggi

Florence, 50141, Italy

RECRUITING

Ematologia - Ospedale Policlinico San Martino S.S.R.L. - IRCCS per l'Oncologia

Genova, 16132, Italy

RECRUITING

Ematologia - Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

Milan, 20133, Italy

RECRUITING

S.C. Ematologia - ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

RECRUITING

UOC Ematologia Oncologica - Istituto Nazionale Tumori - IRCCS Fondazione G. Pascale

Naples, 80131, Italy

RECRUITING

SCDU Ematologia - AOU Maggiore della Carità di Novara

Novara, 28100, Italy

RECRUITING

Divisione di Ematologia - A.O. Ospedali Riuniti Villa Sofia-Cervello

Palermo, 90146, Italy

RECRUITING

Divisione di Ematologia - IRCCS Policlinico S. Matteo di Pavia

Pavia, 27100, Italy

RECRUITING

Ematologia - Ospedale delle Croci

Ravenna, 48121, Italy

RECRUITING

Ematologia - Azienda Unitа Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova

Reggio Emilia, 42123, Italy

RECRUITING

U.O. di Ematologia - Ospedale degli Infermi di Rimini

Rimini, 47923, Italy

RECRUITING

Dipartimento di Medicina Traslazionale e di Precisione - Policlinico Umberto I - Università "La Sapienza" Istituto Ematologia

Roma, 00161, Italy

RECRUITING

U.O. Ematologia - Istituto Clinico Humanitas

Rozzano, 20089, Italy

RECRUITING

S.C. Ematologia Universitaria - A.O.U. Città della Salute e della Scienza di Torino

Torino, 10126, Italy

RECRUITING

S.C di Ematologia - Ospedale Ca Foncello

Treviso, 31100, Italy

RECRUITING

U.O.C Ematologia e Trapianto - A.O. C. Panico

Tricase, 73039, Italy

RECRUITING

SC Ematologia - Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI)

Trieste, 34121, Italy

RECRUITING

U.O. Ematologia - AOU Integrata di Verona

Verona, 37134, Italy

RECRUITING

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

loncastuximab tesirine; Cytarabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Marco Ladetto

  S.C. Ematologia - A.S.O. "SS Antonio e Biagio e Cesare Arrigo" di Alessandria

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stefania Badiali

CONTACT

+39.059.9769912; sbadiali@filinf.it

Giorgio Priolo

CONTACT

+39.0131.033175; gpriolo@filinf.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, multicenter, phase II single arm study

Study Record Dates

• First Submitted: February 3, 2022
• First Posted: February 22, 2022
• Study Start: March 21, 2022
• Primary Completion: March 21, 2026
• Study Completion (Estimated): March 1, 2029
• Last Updated: January 5, 2026

Record last verified: 2025-12

Locations

IT (21)