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

• Status: Not yet recruiting
• Trial end date: 2027-02-01
• Target enrollment: 0
• Participant gender: All

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 (FIL).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fondazione Italiana Linfomi ONLUS
• Treatments: Bendamustine Hydrochloride; Loncastuximab tesirine; Rituximab

Criteria

Inclusion Criteria:

• Histologically documented diagnosis of MCL as defined in the 2017 edition of the World Health Organization (WHO) classification

• Age ≥ 18 and < 80 years

• Relapsed/Refractory disease after one, two or three lines of treatment

• Bendamustine-naive or relapsed after at least two years 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.

• 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 16 weeks after last ADCT-402 dose. A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include but are not limited to hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for continuous 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. The investigator or a designated associate is requested to advise the patient how to achieve highly effective birth control method (failure rate of less than 1%) e.g. intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner. The use of condoms by male patients is required (even if surgically sterilized, i.e., status post vasectomy) unless the female partner is permanently sterile. Full sexual abstinence is admitted when this is in line with the preferred and usual lifestyle of the subject, for the same time period planned for other methods of birth control (see above). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods for the female partner) and withdrawal are not acceptable methods of contraception).

Exclusion Criteria:

• Subjects who have received a bendamustine containing regimen and relapsed less than two years 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 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).

• 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 (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.