Ireland
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Active, not recruiting Phase 2

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

NCT05249959 · tracked via the Priya Life Science Italy tracker
Phase
Phase 2
Started
2022-03-21
Last updated
2026-08-24

Condition(s) studied

Relapsed Mantle Cell LymphomaRefractory Mantle Cell Lymphoma

Investigational drug(s) / intervention(s)

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

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

Study 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).

Eligibility

Sex
ALL
Min age
18 Years
Max age
79 Years
Healthy volunteers
No
Inclusion Criteria: * 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) * Bilirubin ≤ 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non- hepatic origin) * 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. * Subject must be able to adhere to the study visit schedule and other protocol requirements. * Life expectancy ≥ 3 months. * 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 10 months after last loncastuximab tesirine (ADCT-402) dose. Men with female partners who are of childbearing potential 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 7 months after last loncastuximab tesirine (ADCT-402) dose. Exclusion Criteria: * 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. * Lymphoma with active CNS (central nervous system) involvement at the time of screening, including leptomeningeal disease. * Congenital long QT syndrome or a corrected QTcF interval of \>480 msec 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 patient inappropriate for study participation or put the patient at risk. * If female, the patient is pregnant or breast-feeding.

Primary outcome measure(s)

  • Progression-Free Survival (PFS) — The primary endpoint will be assessed from the beginning of the study up to 36 months.
    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.

Trial sites (19)

FacilityCityRegionStatus
ASST Spedali Civili di Brescia Brescia Italy
S.C. Ematologia - A.S.O. "SS Antonio e Biagio e Cesare Arrigo" Alessandria Italy
S.C. di Ematologia - A.O. S. Croce e Carle Cuneo Italy
Unità funzionale di Ematologia - Azienda Ospedaliera Universitaria Careggi Florence Italy
Ematologia - Ospedale Policlinico San Martino S.S.R.L. - IRCCS per l'Oncologia Genova Italy
S.C. Ematologia - ASST Grande Ospedale Metropolitano Niguarda Milan Italy
UOC Ematologia Oncologica - Istituto Nazionale Tumori - IRCCS Fondazione G. Pascale Naples Italy
SCDU Ematologia - AOU Maggiore della Carità di Novara Novara Italy
Divisione di Ematologia - A.O. Ospedali Riuniti Villa Sofia-Cervello Palermo Italy
Divisione di Ematologia - IRCCS Policlinico S. Matteo di Pavia Pavia Italy
Ematologia - Ospedale delle Croci Ravenna Italy
Ematologia - Azienda Unitа Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova Reggio Emilia Italy
U.O. di Ematologia - Ospedale degli Infermi di Rimini Rimini Italy
Dipartimento di Medicina Traslazionale e di Precisione - Policlinico Umberto I - Università "La Sapienza" Istituto Ematologia Roma Italy
U.O. Ematologia - Istituto Clinico Humanitas Rozzano Italy
S.C. Ematologia Universitaria - A.O.U. Città della Salute e della Scienza di Torino Torino Italy
S.C di Ematologia - Ospedale Ca Foncello Treviso Italy
SC Ematologia - Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) Trieste Italy
U.O. Ematologia - AOU Integrata di Verona Verona Italy
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05249959 on ClinicalTrials.gov ↗ ← All trials in Italy