Recruiting

Phase 1

Phase 2

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

Sponsor:

University of Utah

Code:

NCT07573436

Conditions

Post-transplant Lymphoproliferative Disorder

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Loncastuximab tesirine

Rituximab or rituximab biosimilar

Study Details

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

Study ID

NCT07573436

Start date

Nov 5, 2026

Status verified date

Nov, 2026

Completion date

Jun, 2031

Anticipated

Primary completion date

Jun, 2030

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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.
For female subjects: Negative pregnancy test or evidence of post-menopausal status. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause or having undergone surgical sterilization (bilateral oophorectomy or hysterectomy). The following age-specific requirements apply:

Women < 50 years of age:

Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and
Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution; or
Underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
Women ≥ 50 years of age:

Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or
Had radiation-induced menopause with last menses >1 year ago; or
Had chemotherapy-induced menopause with last menses >1 year ago; or
Underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
Female subjects of childbearing potential and male subjects with a sexual partner of childbearing potential must agree to use a highly effective method of contraception and the lactation requirements as described in Sections 5.4.1 and 5.4.2.
Subjects or their legal representatives must be able to read, understand, and provide informed consent to participate in the trial.
Willing and capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol

Exclusion Criteria:

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.
Congenital long QT syndrome or a corrected QT measure (QTc) interval of >480 ms at screening (unless secondary to pacemaker or bundle branch block).
Grade 2 or higher edema (peripheral, pleural or ascites)
Grade 1 or higher pericardial effusion
Severe pulmonary disease
Uncontrolled diabetes mellitus
Severely immunocompromised state
Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
Active systemic bacterial, viral, fungal, or other infection requiring systemic treatment at time of screening
Subjects with evidence of active hepatitis B infection, based on positive surface antigen or Hepatitis B DNA PCR are excluded. Subjects who are Hepatitis B core antibody positive must take prophylaxis with entecavir or equivalent and be willing to undergo monthly Hepatitis B DNA PCR testing
Active hepatitis C infection
Grade 2 or higher rash
Clinically significant fluid accumulation in the third space
Subjects taking prohibited medications as described in Section 6.8.1. A washout period of prohibited medications for a period of at least five half-lives or as clinically indicated should occur before the start of treatment.

Study Design

Enrollment

23 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Dose Level 1 (starting dose): SD or PD

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.

experimental: Dose Level 1 (starting dose): PR

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).

experimental: Dose Level 1 (starting dose): CR

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).

experimental: Dose Level 2: SD or PD

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

experimental: Dose Level 2: PR

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

experimental: Dose Level 2: CR

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

Interventions

Loncastuximab tesirine

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

Rituximab or rituximab biosimilar

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)

Primary outcome measure

Phase I: Define Maximum Tolerated Dose (MTD) based on the rate of dose-limiting toxicities (DLTs) during the DLT evaluation period. [ Time Frame: 4 years ]
Phase II: The complete response (CR) rate after 4 cycles of lonca-R per Lugano 2014 criteria1. [ Time Frame: 4 years ]

Central Contacts and Locations

Central contacts

David Samuel

801-587-4713 david.samuel@hci.utah.edu

Narendranath Epperla, MD

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

Locations

Huntsman Cancer Institute at University of Utah

Recruiting

Salt Lake City, Utah, United States, 84112

Contacts

David Samuel

801-587-4713 david.samuel@hci.utah.edu

More Information

Sponsor

University of Utah

Last update posted

Nov 9, 2026

Last verified

Nov, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-11-10. This information was provided to ClinicalTrials.gov by University of Utah on 2026-11-09. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.