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

Timothy Voorhees

Status and phase

Enrolling

Phase 2

Conditions

Monomorphic B-Cell Post-Transplant Lymphoproliferative Disorder

Polymorphic Post-Transplant Lymphoproliferative Disorder

Treatments

Procedure: Positron Emission Tomography

Biological: Tafasitamab

Procedure: Biopsy

Biological: Rituximab

Procedure: Computed Tomography

Procedure: Biospecimen Collection

Study type

Interventional

Funder types

Other

Identifiers

NCT05786040

NCI-2023-02048 (Registry Identifier)

OSU-22114

Details and patient eligibility

About

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.

Full 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.

Enrollment

28 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

28 participants in 1 patient group

Treatment (tafasitamab, rituximab)

Experimental group

Description: