- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06040320
Polatuzumab Vedotin (Pola) Plus Rituximab (R) in Patients With Post-transplant Lymphoproliferative Disorder (PTLD)
A Phase I/II Study of Frontline Therapy With Polatuzumab Vedotin (Pola) Plus Rituximab (R) in Patients With Post-transplant Lymphoproliferative Disorder (PTLD)
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Neha Mehta-Shah, M.D.
- Phone Number: 314-747-7510
- Email: mehta-n@wustl.edu
Study Locations
-
-
Missouri
-
Saint Louis, Missouri, United States, 63110
- Recruiting
- Washington University School of Medicine
-
Contact:
- Neha Mehta-Shah, M.D.
- Phone Number: 314-747-7510
- Email: mehta-n@wustl.edu
-
Principal Investigator:
- Neha Mehta-Shah, M.D.
-
Sub-Investigator:
- Nancy Bartlett, M.D.
-
Sub-Investigator:
- Fei Wan, Ph.D.
-
Sub-Investigator:
- Brad Kahl, M.D.
-
Sub-Investigator:
- Imran Nizamuddin, M.D.
-
Sub-Investigator:
- Marianna Ruzinova, M.D.
-
Sub-Investigator:
- Laura Flynn, PharmD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Polatuzumab vedotin + Rituximab (Safety Lead-in Low Risk/Interim Complete Remission)
|
Given at 1.8 mg/kg
Other Names:
Given at 375 mg/m^2
Other Names:
|
Experimental: Polatuzumab vedotin + Rituximab (Expansion Low Risk/Interim Complete Remission)
|
Given at 1.8 mg/kg
Other Names:
Given at 375 mg/m^2
Other Names:
|
Experimental: Polatuzumab vedotin + Rituximab + CHP (Safety Lead-in High Risk/Lack of Interim Complete Remission))
|
Given at 1.8 mg/kg
Other Names:
Given at 375 mg/m^2
Other Names:
Cyclophosphamide (750 mg/m^2) + doxorubicin (50 mg/m^2) + prednisone (100 mg days 2-6)
|
Experimental: Polatuzumab vedotin + Rituximab + CHP (Expansion High Risk/Lack of Interim Complete Remission)
|
Given at 1.8 mg/kg
Other Names:
Given at 375 mg/m^2
Other Names:
Cyclophosphamide (750 mg/m^2) + doxorubicin (50 mg/m^2) + prednisone (100 mg days 2-6)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
|
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)
Time Frame: From start of treatment through cycle 2 (estimated to be 42 days, each cycle is 21 days)
|
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
Time Frame: Through completion of treatment (estimated to be 4-6 months)
|
Through completion of treatment (estimated to be 4-6 months)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Complete metabolic response (CR) rate by PET/CT
Time Frame: After cycle 2 (estimated to be day 42, each cycle is 21 days)
|
-Per Lugano Response Criteria
|
After cycle 2 (estimated to be day 42, each cycle is 21 days)
|
Complete metabolic response (CR) rate by PET/CT
Time Frame: End of treatment (estimated to be between 4-6 months)
|
-Per Lugano Response Criteria
|
End of treatment (estimated to be between 4-6 months)
|
Overall response rate (ORR)
Time Frame: End of treatment (estimated to be between 4-6 months)
|
|
End of treatment (estimated to be between 4-6 months)
|
Best overall response
Time Frame: Through completion of treatment (estimated to be between 4-6 months)
|
|
Through completion of treatment (estimated to be between 4-6 months)
|
Duration of response
Time Frame: Through 5 years from completion of treatment (estimated to be between 64 and 66 months)
|
|
Through 5 years from completion of treatment (estimated to be between 64 and 66 months)
|
Progression-free survival (PFS)
Time Frame: Through 5 years from completion of treatment (estimated to be between 64 and 66 months)
|
|
Through 5 years from completion of treatment (estimated to be between 64 and 66 months)
|
Overall survival (OS)
Time Frame: Through 5 years from completion of treatment (estimated to be between 64 and 66 months)
|
-Overall Survival: The time from initiation of treatment to death.
|
Through 5 years from completion of treatment (estimated to be between 64 and 66 months)
|
Collaborators and Investigators
Investigators
- Principal Investigator: Neha Mehta-Shah, M.D., Washington University School of Medicine
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 202308116
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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