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

Primary Purpose

Post-transplant Lymphoproliferative Disorder

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Polatuzumab vedotin
Rituximab
CHP
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Post-transplant Lymphoproliferative Disorder focused on measuring PTLD, Non-Hodgkin's lymphoma, Risk stratification, Front-line

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Washington University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

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

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

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

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

Arm Description

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).

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).

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).

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).

Outcomes

Primary Outcome Measures

Frequency and severity of treatment-related adverse events (AEs)
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.
Rate of completion of the regimen

Secondary Outcome Measures

Complete metabolic response (CR) rate by PET/CT
-Per Lugano Response Criteria
Complete metabolic response (CR) rate by PET/CT
-Per Lugano Response Criteria
Overall response rate (ORR)
Per Lugano Response Criteria Overall Response Rate: The proportion of patients who have a complete or partial response to therapy.
Best overall response
Per Lugano Response Criteria Best Overall Response: Best response recorded from start of treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started).
Duration of response
Per Lugano Response Criteria Duration of Response: The time from onset of response to disease progression or death in patients who achieve complete or partial response.
Progression-free survival (PFS)
Per Lugano Response Criteria Progression-Free Survival: The time from initiation of treatment to the occurrence of disease progression or death.
Overall survival (OS)
-Overall Survival: The time from initiation of treatment to death.

Full Information

First Posted
September 9, 2023
Last Updated
October 5, 2023
Sponsor
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT06040320
Brief Title
Polatuzumab Vedotin (Pola) Plus Rituximab (R) in Patients With Post-transplant Lymphoproliferative Disorder (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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 4, 2023 (Actual)
Primary Completion Date
May 31, 2026 (Anticipated)
Study Completion Date
May 31, 2031 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post-transplant Lymphoproliferative Disorder
Keywords
PTLD, Non-Hodgkin's lymphoma, Risk stratification, Front-line

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Polatuzumab vedotin + Rituximab (Safety Lead-in Low Risk/Interim Complete Remission)
Arm Type
Experimental
Arm Description
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).
Arm Title
Polatuzumab vedotin + Rituximab (Expansion Low Risk/Interim Complete Remission)
Arm Type
Experimental
Arm Description
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).
Arm Title
Polatuzumab vedotin + Rituximab + CHP (Safety Lead-in High Risk/Lack of Interim Complete Remission))
Arm Type
Experimental
Arm Description
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).
Arm Title
Polatuzumab vedotin + Rituximab + CHP (Expansion High Risk/Lack of Interim Complete Remission)
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Polatuzumab vedotin
Other Intervention Name(s)
Polivy
Intervention Description
Given at 1.8 mg/kg
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
Given at 375 mg/m^2
Intervention Type
Drug
Intervention Name(s)
CHP
Intervention Description
Cyclophosphamide (750 mg/m^2) + doxorubicin (50 mg/m^2) + prednisone (100 mg days 2-6)
Primary Outcome Measure Information:
Title
Frequency and severity of treatment-related adverse events (AEs)
Time Frame
From start of treatment through 30 days after completion of treatment (estimated to be 5-7 months)
Title
Number of dose-limiting toxicities (DLTs) (Safety Lead-In Cohort only)
Description
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.
Time Frame
From start of treatment through cycle 2 (estimated to be 42 days, each cycle is 21 days)
Title
Rate of completion of the regimen
Time Frame
Through completion of treatment (estimated to be 4-6 months)
Secondary Outcome Measure Information:
Title
Complete metabolic response (CR) rate by PET/CT
Description
-Per Lugano Response Criteria
Time Frame
After cycle 2 (estimated to be day 42, each cycle is 21 days)
Title
Complete metabolic response (CR) rate by PET/CT
Description
-Per Lugano Response Criteria
Time Frame
End of treatment (estimated to be between 4-6 months)
Title
Overall response rate (ORR)
Description
Per Lugano Response Criteria Overall Response Rate: The proportion of patients who have a complete or partial response to therapy.
Time Frame
End of treatment (estimated to be between 4-6 months)
Title
Best overall response
Description
Per Lugano Response Criteria Best Overall Response: Best response recorded from start of treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started).
Time Frame
Through completion of treatment (estimated to be between 4-6 months)
Title
Duration of response
Description
Per Lugano Response Criteria Duration of Response: The time from onset of response to disease progression or death in patients who achieve complete or partial response.
Time Frame
Through 5 years from completion of treatment (estimated to be between 64 and 66 months)
Title
Progression-free survival (PFS)
Description
Per Lugano Response Criteria Progression-Free Survival: The time from initiation of treatment to the occurrence of disease progression or death.
Time Frame
Through 5 years from completion of treatment (estimated to be between 64 and 66 months)
Title
Overall survival (OS)
Description
-Overall Survival: The time from initiation of treatment to death.
Time Frame
Through 5 years from completion of treatment (estimated to be between 64 and 66 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Neha Mehta-Shah, M.D.
Phone
314-747-7510
Email
mehta-n@wustl.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Neha Mehta-Shah, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Neha Mehta-Shah, M.D.
Phone
314-747-7510
Email
mehta-n@wustl.edu
First Name & Middle Initial & Last Name & Degree
Neha Mehta-Shah, M.D.
First Name & Middle Initial & Last Name & Degree
Imran Nizamuddin, M.D.
First Name & Middle Initial & Last Name & Degree
Brad Kahl, M.D.
First Name & Middle Initial & Last Name & Degree
Nancy Bartlett, M.D.
First Name & Middle Initial & Last Name & Degree
Marianna Ruzinova, M.D.
First Name & Middle Initial & Last Name & Degree
Fei Wan, Ph.D.
First Name & Middle Initial & Last Name & Degree
Laura Flynn, PharmD

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Learn more about this trial

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

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