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

NCT06040320 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202308116
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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

Keywords

PTLD; Non-Hodgkin's lymphoma; Risk stratification; Front-line

Outcome Measures

Primary Outcomes (3)

• Frequency and severity of treatment-related adverse events (AEs)

  From start of treatment through 30 days after completion of treatment (estimated to be 5-7 months)

• Number of dose-limiting toxicities (DLTs) (Safety Lead-In Cohort only)

  A dose-limiting toxicity (DLT) is defined as an occurrence of an adverse event delineated by the protocol that is at least possibly related to polatuzumab vedotin, rituximab, or the combination within Cycle 1 or Cycle 2.

  From start of treatment through cycle 2 (estimated to be 42 days, each cycle is 21 days)

• Rate of completion of the regimen

  Through completion of treatment (estimated to be 4-6 months)

Secondary Outcomes (7)

• Complete metabolic response (CR) rate by PET/CT

  After cycle 2 (estimated to be day 42, each cycle is 21 days)

• Complete metabolic response (CR) rate by PET/CT

  End of treatment (estimated to be between 4-6 months)

• Overall response rate (ORR)

  End of treatment (estimated to be between 4-6 months)

• Best overall response

  Through completion of treatment (estimated to be between 4-6 months)

• Duration of response

  Through 5 years from completion of treatment (estimated to be between 64 and 66 months)

Study Arms (4)

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

EXPERIMENTAL

* 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).

Drug: Polatuzumab vedotin; Drug: Rituximab

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

EXPERIMENTAL

* 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).

Drug: Polatuzumab vedotin; Drug: Rituximab

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

EXPERIMENTAL

* 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).

Drug: Polatuzumab vedotin; Drug: Rituximab; Drug: CHP

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

EXPERIMENTAL

* 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).

Drug: Polatuzumab vedotin; Drug: Rituximab; Drug: CHP

Interventions

Polatuzumab vedotin DRUG

Given at 1.8 mg/kg

Also known as: Polivy

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

Rituximab DRUG

Given at 375 mg/m\^2

Also known as: Rituxan

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

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

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Links

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

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

polatuzumab vedotin; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

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

• Neha Mehta-Shah, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Neha Mehta-Shah, M.D.

CONTACT

314-747-7510; mehta-n@wustl.edu

Study Design

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

Study Record Dates

• First Submitted: September 9, 2023
• First Posted: September 15, 2023
• Study Start: October 4, 2023
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2032
• Last Updated: October 28, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)