Loncastuximab Tesirine and Rituximab as First-line Therapy in Patients With Post-transplant Lymphoproliferative Disorder (PLUTO)

NCT07573436 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HCI198713
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of phase I of this clinical trial is to learn the recommended dose of the drugs loncastuximab tesirine and rituximab in participants with post-transplant lymphoproliferative disorders (PTLD). The purpose of phase II of this clinical trial is to learn if the drugs loncastuximab tesirine and rituximab are effective in participants with post-transplant lymphoproliferative disorders (PTLD).

Conditions

Post-transplant Lymphoproliferative Disorder

Outcome Measures

Primary Outcomes (2)

• Phase I: Define Maximum Tolerated Dose (MTD) based on the rate of dose-limiting toxicities (DLTs) during the DLT evaluation period.

  To assess the Recommended Phase 2 Dose (RP2D) of loncastuximab tesirine and rituximab in participants with post-transplant lymphoproliferative disorders (PTLD).

  4 years

• Phase II: The complete response (CR) rate after 4 cycles of lonca-R per Lugano 2014 criteria1.

  To assess the efficacy of the combination of lonca-R based on CR rate after 4 cycles.

  4 years

Secondary Outcomes (5)

• The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type, severity (as defined by the NIH CTCAE, version 6.0), seriousness, duration, and relationship to study treatment.

  4 years

• The overall response rate (ORR) after 4 cycles of lonca-R.

  4 years

• The best complete response (CR) rate is defined as CR at the completion of 4 cycles of lonca-R or 4 cycles of lonca-R and 4 cycles of consolidation of rituximab monotherapy (every 3 weeks) in subjects with B-cell PTLD.

  4 years

• Median and two year progression-free survival (PFS). PFS will be as defined as the time from study drug initiation to the time of documented disease progression (as assessed by Lugano Criteria), or death from any cause.

  4 years

• Median and two year overall survival (OS). OS is defined as the time from initiation of treatment until death from any cause.

  4 years

Study Arms (6)

Dose Level 1 (starting dose): SD or PD

EXPERIMENTAL

Dose Level 1: * Loncastuximab tesirine: 0.075 mg/kg IV every 3 weeks * Rituximab: 375 mg/m2 IV This arm included participants who had SD (Stable Disease) or PD (Progressive Disease) after the first 6 weeks of treatment. Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they do not achieve a response, they will come off the study but will be monitored for survival.

Drug: Loncastuximab tesirine; Drug: Rituximab or rituximab biosimilar

Dose Level 1 (starting dose): PR

EXPERIMENTAL

Dose Level 1: * Loncastuximab tesirine: 0.075 mg/kg IV every 3 weeks * Rituximab: 375 mg/m2 IV This arm included participants who had a Partial Response (PR) after the first 6 weeks of treatment. Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they achieve PR, they will have the option to receive either rituximab consolidation or R-CHOP (at the physician's discretion).

Drug: Loncastuximab tesirine; Drug: Rituximab or rituximab biosimilar

Dose Level 1 (starting dose): CR

EXPERIMENTAL

Dose Level 1: * Loncastuximab tesirine: 0.075 mg/kg IV every 3 weeks * Rituximab: 375 mg/m2 IV This arm included participants who had a Complete Response (CR) after the first 6 weeks of treatment. Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they achieve a CR after 4 cycles of Lonca-R, they will receive rituximab consolidation (SOC).

Drug: Loncastuximab tesirine; Drug: Rituximab or rituximab biosimilar

Dose Level 2: SD or PD

EXPERIMENTAL

Dose Level 2: * Loncastuximab tesirine: 0.15 mg/kg IV every 3 weeks for the first 2 cycles, then 0.075 mg/kg starting C3 * Rituximab: 375 mg/m2 IV This arm included participants who had SD (Stable Disease) or PD (Progressive Disease) after the first 6 weeks of treatment. Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they do not achieve a response, they will come off the study but will be monitored for survival.

Drug: Loncastuximab tesirine; Drug: Rituximab or rituximab biosimilar

Dose Level 2: PR

EXPERIMENTAL

Dose Level 2: * Loncastuximab tesirine: 0.15 mg/kg IV every 3 weeks for the first 2 cycles, then 0.075 mg/kg starting C3 * Rituximab: 375 mg/m2 IV This arm included participants who had a Partial Response (PR) after the first 6 weeks of treatment. Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they achieve PR, they will have the option to receive either rituximab consolidation or R-CHOP (at the physician's discretion).

Drug: Loncastuximab tesirine; Drug: Rituximab or rituximab biosimilar

Dose Level 2: CR

EXPERIMENTAL

Dose Level 2: * Loncastuximab tesirine: 0.15 mg/kg IV every 3 weeks for the first 2 cycles, then 0.075 mg/kg starting C3 * Rituximab: 375 mg/m2 IV This arm included participants who had a Complete Response (CR) after the first 6 weeks of treatment. Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they achieve a CR after 4 cycles of Lonca-R, they will receive rituximab consolidation (SOC).

Drug: Loncastuximab tesirine; Drug: Rituximab or rituximab biosimilar

Interventions

Loncastuximab tesirine DRUG

Lonca will be administered by IV at 75µg/kg every 3 weeks (DL1).

Dose Level 1 (starting dose): CR; Dose Level 1 (starting dose): PR; Dose Level 1 (starting dose): SD or PD; Dose Level 2: CR; Dose Level 2: PR; Dose Level 2: SD or PD

Rituximab or rituximab biosimilar DRUG

Rituximab or rituximab biosimilar will be administered by IV at 375 mg/m2 on Day 1 of every cycle. Lonca will be administered first, followed by rituximab (with a 30 min wait time between the two agents)

Also known as: RITUXAN, Truxima, Ruxience, Riabni

Dose Level 1 (starting dose): CR; Dose Level 1 (starting dose): PR; Dose Level 1 (starting dose): SD or PD; Dose Level 2: CR; Dose Level 2: PR; Dose Level 2: SD or PD

Eligibility Criteria

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

You may qualify if:

• Subject aged ≥ 18 years.
• Histologically confirmed B-cell PTLD (monomorphic and polymorphic) following solid organ transplantation; with or without EBV association.
• Note: Subjects with classic Hodgkin-like PTLD are excluded.
• Measurable disease as defined by the 2014 Lugano Classification as assessed by positron-emission tomography (PET)- computed tomography (CT) or by CT or magnetic resonance imaging (MRI) if the tumor is not fluorodeoxyglucose (FDG)-avid on screening
• ECOG Performance Status ≤ 2.
• Adequate organ function as defined as:
• Hematologic:
• Absolute neutrophil count (ANC) ≥ 1000/mm3
• Platelet count ≥ 75,000/mm3
• Hemoglobin ≥ 8 g/dL
• Hepatic:
• Bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN with document liver involvement and/ or Gilbert's disease
• Transaminases (AST or ALT) ≤ 3 x ULN or ≤ 5 x ULN with documented liver involvement
• Renal:
• Estimated creatinine clearance ≥ 60 mL/min by Cockcroft-Gault formula.

You may not qualify if:

• PTLD following liquid transplantation
• CNS involvement
• Prior treatment for PTLD with the exception of radiation, antivirals, steroids and reduced immunosuppression
• Human immunodeficiency virus (HIV) infection
• Major surgery within 4 weeks prior to enrolment
• History of bleeding diathesis (e.g., von Willebrand's disease), hemophilia, or active bleeding.
• Subjects with chronic liver disease with hepatic impairment Child-Pugh class C
• Pregnant or lactating or intending to become pregnant during the study
• Active autoimmune disease which, in the opinion of the investigator, may negatively impact subject safety or interfere with study participation.
• The diagnosis of another malignancy which, in the opinion of the investigator, is likely to negatively impact subject safety or interfere with study participation.
• Significant medical diseases or conditions including those requiring substantial changes in concomitant medications, as assessed by the investigator, that would substantially increase the risk-to-benefit ratio of participating in the study. This includes, but is not limited to the following conditions:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class III or IV, unstable angina pectoris, serious cardiac arrhythmias.
• Myocardial infarction (MI) within 6 months before the first dose.
• QTc prolongation defined as a QTcF \> 480 ms.

Sponsors & Collaborators

• University of Utah: lead
• ADC Therapeutics S.A.: collaborator

Study Sites (1)

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Interventions

loncastuximab tesirine; Rituximab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Narendranath Epperla, MD

  Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachel Kingsford

CONTACT

801-585-0115; rachel.kingsford@hci.utah.edu

Narendranath Epperla, MD

CONTACT

801-585-0255; naren.epperla@hci.utah.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2026
• First Posted: May 7, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2031
• Last Updated: May 7, 2026

Record last verified: 2026-04

Locations

US (1)