RECRUITING

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

Conditions

Post-transplant Lymphoproliferative Disorder PTLD Non-Hodgkin's lymphoma Risk stratification Front-line

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase I/II Study of Frontline Therapy With Polatuzumab Vedotin (Pola) Plus Rituximab (R) in Patients With Post-transplant Lymphoproliferative Disorder (PTLD)

Quick Facts

Study Start:2023-10-04

Study Completion:2031-05-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06040320

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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.

Inclusion Criteria

Exclusion 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.

* 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.

Contacts and Locations

Study Contact

Neha Mehta-Shah, M.D.

CONTACT

314-747-7510

mehta-n@wustl.edu

Principal Investigator

Neha Mehta-Shah, M.D.

PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Study Locations (Sites)

Washington University School of Medicine

Saint Louis, Missouri, 63110

United States

Collaborators and Investigators

Sponsor: Washington University School of Medicine

Neha Mehta-Shah, M.D., PRINCIPAL_INVESTIGATOR, Washington University School of Medicine

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-10-04

Study Completion Date2031-05-31

Study Record Updates

Study Start Date2023-10-04

Study Completion Date2031-05-31

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

Post-transplant Lymphoproliferative Disorder