Polatuzumab Vedotin (Pola) Plus Rituximab (R) in Patients With Post-transplant Lymphoproliferative Disorder (PTLD)

NCT ID: NCT06040320

Last Updated: 2025-10-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-04
• Study Completion Date: 2032-05-31

Brief Summary

This study will test polatuzumab vedotin in combination with rituximab in patients with treatment-naïve CD20-positive post-transplant lymphoproliferative disorder (PTLD) based on the established efficacy of polatuzumab vedotin in B-cell lymphomas and the inadequate response rate of PTLD to single-agent rituximab. The hypothesis is that this combination therapy will be safe, well-tolerated, and effective. If so, patients with PTLD will be able to be spared the toxicity of anthracycline-based chemotherapy. Additionally, the role of the tumor microenvironment and the role of anellovirus, a non-human pathogen virus, will be explored as prognostic markers in PTLD.

Conditions

Post-transplant Lymphoproliferative Disorder

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Polatuzumab vedotin + Rituximab (Safety Lead-in Low Risk/Interim Complete Remission)

• Cycle 1 (21 days)

• Day 1: polatuzumab vedotin + rituximab
• Day 8: rituximab
• Day 15: rituximab
• Cycle 2 (21 days)

• Day 1: polatuzumab vedotin + rituximab
• After Cycle 2, a response assessment will be performed. Patients who show a complete response (and are therefore determined to be low risk) will continue to receive polatuzumab vedotin + rituximab on Day 1 of each 21-day cycle for 4 additional cycles (6 cycles of treatment total).

Group Type: EXPERIMENTAL

Polatuzumab vedotin

Intervention Type: DRUG

Given at 1.8 mg/kg

Rituximab

Intervention Type: DRUG

Given at 375 mg/m\^2

Polatuzumab vedotin + Rituximab (Expansion Low Risk/Interim Complete Remission)

• Cycle 1 (21 days)

• Day 1: polatuzumab vedotin + rituximab
• Day 8: rituximab
• Day 15: rituximab
• Cycle 2 (21 days)

• Day 1: polatuzumab vedotin + rituximab
• After Cycle 2, a response assessment will be performed. Patients who show a complete response (and are therefore determined to be low risk) will continue to receive polatuzumab vedotin + rituximab on Day 1 of each 21-day cycle for 4 additional cycles (6 cycles of treatment total).

Group Type: EXPERIMENTAL

Polatuzumab vedotin

Intervention Type: DRUG

Given at 1.8 mg/kg

Rituximab

Intervention Type: DRUG

Given at 375 mg/m\^2

Polatuzumab vedotin + Rituximab + CHP (Safety Lead-in High Risk/Lack of Interim Complete Remission))

• Cycle 1 (21 days)

• Day 1: polatuzumab vedotin + rituximab
• Day 8: rituximab
• Day 15: rituximab
• Cycle 2 (21 days)

• Day 1: polatuzumab vedotin + rituximab
• After Cycle 2, a response assessment will be performed. Patients who show anything other than a complete response (and are therefore determined to be high risk) will receive polatuzumab vedotin + rituximab + CHP (cyclophosphamide + doxorubicin + prednisone) on Day 1 of each 21-day cycle for 4 additional cycles, followed by 2 final cycles of CHP alone on Day 1 (8 cycles of treatment total).

Group Type: EXPERIMENTAL

Polatuzumab vedotin

Intervention Type: DRUG

Given at 1.8 mg/kg

Rituximab

Intervention Type: DRUG

Given at 375 mg/m\^2

CHP

Intervention Type: DRUG

Cyclophosphamide (750 mg/m\^2) + doxorubicin (50 mg/m\^2) + prednisone (100 mg days 2-6)

Polatuzumab vedotin + Rituximab + CHP (Expansion High Risk/Lack of Interim Complete Remission)

• Cycle 1 (21 days)

• Day 1: polatuzumab vedotin + rituximab
• Day 8: rituximab
• Day 15: rituximab
• Cycle 2 (21 days)

• Day 1: polatuzumab vedotin + rituximab
• After Cycle 2, a response assessment will be performed. Patients who show anything other than a complete response (and are therefore determined to be high risk) will receive polatuzumab vedotin + rituximab + CHP (cyclophosphamide + doxorubicin + prednisone) on Day 1 of each 21-day cycle for 4 additional cycles, followed by 2 final cycles of CHP alone on Day 1 (8 cycles of treatment total).

Group Type: EXPERIMENTAL

Polatuzumab vedotin

Intervention Type: DRUG

Given at 1.8 mg/kg

Rituximab

Intervention Type: DRUG

Given at 375 mg/m\^2

CHP

Intervention Type: DRUG

Cyclophosphamide (750 mg/m\^2) + doxorubicin (50 mg/m\^2) + prednisone (100 mg days 2-6)

Interventions

Polatuzumab vedotin

Given at 1.8 mg/kg

Intervention Type: DRUG

Rituximab

Given at 375 mg/m\^2

Intervention Type: DRUG

CHP

Cyclophosphamide (750 mg/m\^2) + doxorubicin (50 mg/m\^2) + prednisone (100 mg days 2-6)

Intervention Type: DRUG

Other Intervention Names

Polivy; Rituxan

Eligibility Criteria

Inclusion Criteria

• Previously untreated biopsy-confirmed CD20-positive monomorphic post-transplant lymphoproliferative disorder (or CD20-positive lymphoma associated with immune deficiency) arising after solid organ or hematopoietic stem cell transplant. This may be defined by either the 2016 World Health Organization classification of lymphoid neoplasms or the 2022 International consensus Classification of Mature Lymphoid Neoplasms or the 2022 World Health Organization classification.
• At least 18 years of age.
• ECOG performance status ≤ 3.
• Adequate hematologic and organ function (unless due to underlying lymphoma per the investigator) as defined below:

• Absolute neutrophil count ≥ 1.0 K/cumm
• Platelets ≥ 75 K/cumm
• Hemoglobin ≥ 8.0 g/dL
• Total bilirubin < 1.5 x IULN
• AST(SGOT)/ALT(SGPT) < 2.5 x IULN
• Creatinine clearance > 30 mL/min measured or by Cockcroft-Gault
• Note: Patients with extensive bone marrow involvement by lymphoma and/or disease-related cytopenias may be enrolled if the following criteria are met:

• ANC ≥ 0.5 K/cumm
• Platelets ≥ 50 K/cumm
• Hemoglobin ≥ 7.0 g/dL
• The effects of polatuzumab vedotin and rituximab on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a participant become pregnant or suspect pregnancy while participating in this study, the participant must inform the treating physician immediately.
• Ability to understand and willingness to sign an IRB approved written informed consent document.

Exclusion Criteria

• Active central nervous system involvement with lymphoma / PTLD.
• Current grade ≥ 2 peripheral neuropathy.
• Current ejection fraction < 40% on transthoracic echocardiogram or multigated acquisition (MUGA) scan
• Subjects with history of concurrent second cancers requiring active, ongoing systemic treatment with the following exceptions:

• Patients with non-melanoma skin cancer or carcinoma in situ of the cervix will not be excluded.
• Patients with previous malignancies are eligible if disease-free for > 2 years.
• Patients on long term hormonal therapy to prevent recurrence of a prior cancer (e.g., hormonal therapy for breast cancer) will not be excluded.
• Currently receiving any other investigational agents or received any investigational agents during the 4 weeks prior to the first dose of polatuzumab vedotin.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to polatuzumab vedotin, rituximab, or other agents used in the study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (bacterial, fungal, viral, parasitic, or mycobacterial), interstitial lung disease, active non-infectious pneumonitis, congestive heart failure NYHA grade ≥ 3, unstable angina pectoris, or cardiac arrhythmia.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to C1D1
• Patients with HIV are eligible provided the meet the following criteria:

• On antiretroviral regimen and stable on that regimen
• Healthy from an HIV perspective
• CD4 count > 250 cells/mcL
• Minimal anticipated interactions or overlapping toxicity with polatuzumab vedotin or rituximab
• HIV viral load < 200 copies/mm3 by standard clinical assays
• Active hepatitis B infection.

• Patients who are hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (HBcAb) positive must be negative for hepatitis B virus (HBV) polymerase chain reaction (PCR) to be eligible for study participation.
• Active hepatitis C infection.

• Patients who are positive for hepatitis C virus (HCV) antibody must be negative for HCV by PCR to be eligible for study participation.
• Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of results.

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

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Neha Mehta-Shah, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Neha Mehta-Shah, M.D.

Role: CONTACT

mehta-n@wustl.edu

314-747-7510

Facility Contacts

Neha Mehta-Shah, M.D.

Role: primary

mehta-n@wustl.edu

314-747-7510

Related Links

http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

202308116

Identifier Type: -

Identifier Source: org_study_id