Tafasitamab and Rituximab for Front-Line Treatment of Post-Transplant Lymphoproliferative Disorder

NCT ID: NCT05786040

Last Updated: 2025-02-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-23
• Study Completion Date: 2025-12-31

Brief Summary

This phase II trial tests how well tafasitamab and rituximab work for front-line treatment of patients with post-transplant lymphoproliferative disorder. Post-transplant lymphoproliferative disorder (PTLD) is the name for types of lymphoma that sometimes develop in people who have had a transplant. It can affect people who are taking medicines to suppress their immune system. Tafasitamab injection is in a class of medications called monoclonal antibodies. It works by helping the body to slow or stop the growth of cancer cells. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Giving the combination of tafasitamab and rituximab may work better in treating patients with post-transplant lymphoproliferative disorder.

Detailed Description

PRIMARY OBJECTIVE:

I. To estimate the rate of complete response (CR) after 4 cycles of weekly (or 7-day) treatments with combined rituximab and tafasitamab in subjects with post-transplant lymphoproliferative disorder (PTLD).

SECONDARY OBJECTIVES:

I. To describe the safety profile of treatment with combined rituximab and tafasitamab in subjects with PTLD.

II. To estimate the objective response rate (ORR), defined as clinical response (CR + partial response [PR]) after 4 cycles of weekly (or 7-day) treatments with combined rituximab and tafasitamab in subjects with PTLD.

III. To determine the best overall response (BOR), defined as best clinical response (CR + PR) at either the completion of 4 cycles of weekly (or 7-day) treatments or 4 consolidation cycles (every 3 week) of combined rituximab and tafasitamab in subjects with PTLD.

IV. To estimate the rate of complete response (CR) after completion of consolidation treatments of combined rituximab and tafasitamab in subjects with PTLD.

V. To estimate the progression free survival (PFS) in subjects with PTLD treated with rituximab and tafasitamab.

VI. To estimate the overall survival (OS) in subjects with PTLD treated with rituximab and tafasitamab.

EXPLORATORY OBJECTIVES:

I. To describe baseline CD19 and CD20 expression on malignant lymphocytes by flow cytometry in subjects with PTLD.

II. To describe the relationship of tumor microenvironment characteristics using ribonucleic acid sequencing (RNASeq) with clinical response to combined rituximab and tafasitamab in subjects with PTLD.

III. To characterize the peripheral immunophenotype changes using cytometry by time-of-flight (CyTOF) from cycle 1 (C1) day 1 (D1) to cycle 5 (C5)D1 of combined rituximab and tafasitamab in subjects with PTLD.

IV. To describe the type of immunosuppression and amount reduced in subjects with PTLD.

V. To describe the relationship between metabolic tumor volume at diagnosis and response to combined rituximab and tafasitamab in subjects with PTLD.

VI. To characterize Epstein-barr virus (EBV) methylation alterations in EBV positive PTLDs.

OUTLINE:

Patients receive tafasitamab intravenously (IV) and rituximab IV or subcutaneously (SC) on study. Patients who have CR or PR after 4 cycles may receive additional tafasitamab and rituximab on study. Patients also undergo positron emission tomography (PET) or computed tomography (CT), biopsy, and collection of blood samples throughout the trial.

Conditions

Monomorphic B-Cell Post-Transplant Lymphoproliferative Disorder; Polymorphic Post-Transplant Lymphoproliferative Disorder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (tafasitamab, rituximab)

Patients receive tafasitamab IV and rituximab IV or SC on study. Patients who have CR or PR after 4 cycles may receive additional tafasitamab and rituximab on study. Patients also undergo PET or CT, biopsy, and collection of blood samples throughout the trial.

Group Type: EXPERIMENTAL

Biopsy

Intervention Type: PROCEDURE

Undergo biopsy

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo collection of blood samples

Computed Tomography

Intervention Type: PROCEDURE

Undergo CT

Positron Emission Tomography

Intervention Type: PROCEDURE

Undergo PET

Rituximab

Intervention Type: BIOLOGICAL

Given IV or SC

Tafasitamab

Intervention Type: BIOLOGICAL

Given IV

Interventions

Biopsy

Undergo biopsy

Intervention Type: PROCEDURE

Biospecimen Collection

Undergo collection of blood samples

Intervention Type: PROCEDURE

Computed Tomography

Undergo CT

Intervention Type: PROCEDURE

Positron Emission Tomography

Undergo PET

Intervention Type: PROCEDURE

Rituximab

Given IV or SC

Intervention Type: BIOLOGICAL

Tafasitamab

Given IV

Intervention Type: BIOLOGICAL

Other Intervention Names

BIOPSY_TYPE; Bx; Biological Sample Collection; Biospecimen Collected; Specimen Collection; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT; CT Scan; tomography; Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; ABP 798; BI 695500; C2B8 Monoclonal Antibody; Chimeric Anti-CD20 Antibody; CT-P10; IDEC-102; IDEC-C2B8; IDEC-C2B8 Monoclonal Antibody; MabThera; Monoclonal Antibody IDEC-C2B8; PF-05280586; Riabni; Rituxan; Rituximab ABBS; Rituximab ARRX; Rituximab Biosimilar ABP 798; Rituximab Biosimilar BI 695500; Rituximab Biosimilar CT-P10; Rituximab Biosimilar GB241; Rituximab Biosimilar IBI301; Rituximab Biosimilar JHL1101; Rituximab Biosimilar PF-05280586; Rituximab Biosimilar RTXM83; Rituximab Biosimilar SAIT101; Rituximab Biosimilar SIBP-02; rituximab biosimilar TQB2303; Rituximab PVVR; rituximab-abbs; Rituximab-arrx; Rituximab-pvvr; RTXM83; Ruxience; Truxima; Immunoglobulin, Anti-(Human Cd19 Antigen) (Human-mus musculus Monoclonal MOR00208 Heavy Chain), Disulfide with Human-mus musculus Monoclonal MOR00208 .Kappa.-chain, Dimer; Monjuvi; MOR-00208; MOR00208; MOR208; Tafasitamab-cxix; XmAb5574

Eligibility Criteria

Inclusion Criteria

• Written informed consent obtained to participate in the study and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information
• Age >= 18 years at the time of consent
• Karnofsky scale > 30% or Eastern Cooperative Oncology Group (ECOG) =< 3 (can be assessed after pre-phase steroids)
• Histological evidence of B-cell PTLD (monomorphic and polymorphic) following solid organ transplantation; expresses CD19 and CD20, with or without EBV association, confirmed after biopsy or resection of tumor
• Measurable disease of > 1.5 cm in diameter and/or bone marrow involvement
• Subjects having undergone heart, lung, liver, kidney, pancreas, small intestine transplantation or a combination of the organ transplantations mentioned
• No prior lines of therapy for PTLD (palliative radiation, steroids, antiviral therapy, and reduction in immunosuppression are allowed)
• Human immunodeficiency virus (HIV) infection is allowed if viral load is undetectable at time of enrollment and CD4+ count > 200 cells/uL
• Expected survival greater than 30 days
• Absolute neutrophil count (ANC) >= 1.0 x 10^9/L (obtained within 14 days prior to initiating study treatment)

• Note: Hematology and other lab parameters that are =< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• Platelets >= 50 x 10^9/L (obtained within 14 days prior to initiating study treatment)

• Note: Hematology and other lab parameters that are =< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• Creatinine clearance (mL/min) >= 30 mL/min (obtained within 14 days prior to initiating study treatment)

• Cockcroft-Gault Equation
• Note: Hematology and other lab parameters that are =< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• Bilirubin =< 3.0 x upper limit of normal (ULN). Subjects with Gilbert's syndrome may be enrolled despite a total bilirubin level > 3.0 mg/dL if their conjugated bilirubin is =< 3.0 x ULN) (obtained within 14 days prior to initiating study treatment)

• Note: Hematology and other lab parameters that are =< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• Aspartate aminotransferase (AST) =< 3.0 x ULN (obtained within 14 days prior to initiating study treatment)

• Note: Hematology and other lab parameters that are =< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• Alanine aminotransferase (ALT) =< 3.0 x ULN (obtained within 14 days prior to initiating study treatment)

• Note: Hematology and other lab parameters that are =< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• Females of childbearing potential must have a negative serum pregnancy test within 3 days prior to registration. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided
• Females of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 12 months after treatment the last dose of rituximab or tafasitamab. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method or an intrauterine device that meets < 1% failure rate for protection from pregnancy in the product label
• Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 12 months after the last dose of rituximab
• Subjects with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the experimental regimen are eligible for the trial
• Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee

Exclusion Criteria

• Uncontrolled active infection. Patients requiring systemic therapy are eligible if the infection is deemed controlled by the investigator
• Post-transplant lymphoproliferative disorder following liquid transplantation
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study and lactating females must agree to not breastfeed while taking study drugs)
• Subjects with central nervous system (CNS) involvement by PTLD
• Uncontrolled concomitant illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV), unstable angina pectoris, myocardial infarction within 1 month prior to enrollment, uncontrolled cardiac arrhythmias, uncontrolled seizures, or severe non-compensated hypertension (systolic blood pressure >= 180 mmHg or diastolic blood pressure >= 120 mmHg)
• History of progressive multifocal leukoencephalopathy
• Active hepatitis B infection with positive viral polymerase chain reaction (PCR) from the blood. Subjects with active hepatitis B infection and undetectable viral PCR from the blood will be allowed with concurrent use of entecavir suppression
• Prior treatment for PTLD with the exception of radiation, antivirals, steroids and reduced immunosuppression
• Electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
• Any condition, including the presence of laboratory values which is deemed by the clinician to place the subject at an unacceptable risk or confounds the ability to interpret the data from this study
• Live virus vaccines must not be administered within 28 days of the start of study treatment
• Any investigational treatments must have been completed at least 7 days prior to the start of study treatment

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Timothy Voorhees

OTHER

Sponsor Role: lead

Responsible Party

Timothy Voorhees

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Timothy J Voorhees, MD, MSCR

Role: PRINCIPAL_INVESTIGATOR

Ohio State University Comprehensive Cancer Center

Locations

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status: RECRUITING

University of North Carolina-Hillsborough Campus

Hillsborough, North Carolina, United States

Site Status: RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

The Ohio State Comprehensive Cancer Center

Role: CONTACT

OSUCCCClinicaltrials@osumc.edu

800-293-5066

Facility Contacts

Anita A. Trupiano

Role: primary

ar2069@cinj.rutgers.edu

732-454-9795

Christopher E. Dittus, DO, MPH

Role: primary

chris_dittus@med.unc.edu

919-966-4431

Elyse Schmidt

Role: backup

elyse_schmidt@med.unc.edu

919-966-4432

Timothy J. Voorhees, MD, MSCR

Role: primary

timothy.voorhees@osumc.edu

614-293-6943

Related Links

http://cancer.osu.edu

The Jamesline

Other Identifiers

NCI-2023-02048

Identifier Type: REGISTRY

Identifier Source: secondary_id

OSU-22114

Identifier Type: -

Identifier Source: org_study_id