Polatuzumab Vedotin in Combination With Chemotherapy in Subjects With Richter's Transformation

NCT04679012 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 20-08022533
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 4

Brief Summary

This study evaluates the effectiveness and safety of Polatuzumab vedotin plus infusional chemoimmunotherapy containing rituximab, etoposide, prednisone, cyclophosphamide and hydroxydaunorubicin. This is a single arm study. Enrolled patients will receive up to six cycles (21-day cycles) of therapy. While on study, subjects will be monitored weekly until end of treatment, then followed for 52 weeks or until disease progression or discontinuation due to toxicity or death. After completion of the 52-week follow-up/End of study visit, Subjects will be followed for an additional 104 week period, with an assessment occurring every 12 weeks to evaluate survival outcomes and next line of treatments only.

Conditions

Richter Syndrome; Chronic Lymphocytic Leukemia

Keywords

Polatuzumab vedotin; CLL; Richter's Transformation

Outcome Measures

Primary Outcomes (1)

• Complete metabolic remission/complete remission (CMR/CR) rate of subjects at end of treatment (EOT)

  Percentage of subjects who achieve CMR/CR on study.

  19 weeks

Secondary Outcomes (5)

• Safety of polatuzumab vedotin plus infusional chemoimmunotherapy (CIT) containing rituximab, etoposide, prednisone, cyclophosphamide and hydroxydaunorubicin in patients with newly diagnosed Richter's Transformation.

  1.5 years

• Overall response rate (ORR)

  3 years

• Progression free survival (PFS)

  3 years

• Overall survival (OS)

  3 years

• Allogeneic transplantation rate in eligible patients

  3 years

Study Arms (1)

Polatuzumab vedotin plus R-EPCH

EXPERIMENTAL

Polatuzumab vedotin will be given in conjunction with 6 cycles of R-EPCH (rituximab, etoposide, prednisone, cyclophosphamide, hydroxydaunorubicin). The dosing schedule and regimen for R-EPCH will follow established protocols. Polatuzumab vedotin will be administered on Day 1 of each 21-day cycle.

Drug: Polatuzumab Vedotin; Drug: Rituximab; Drug: Etoposide; Drug: Prednisone; Drug: Cyclophosphamide; Drug: Hydroxydaunomycin

Interventions

Polatuzumab Vedotin DRUG

Polatuzumab vedotin will be administered as an IV infusion at 1.8mg/kg on Day 1 of each cycle, every 21 days.

Also known as: Polivy

Polatuzumab vedotin plus R-EPCH

Rituximab DRUG

Rituximab will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.

Also known as: Rituxan, chimeric anti-CD20 monoclonal antibody

Polatuzumab vedotin plus R-EPCH

Etoposide DRUG

Etoposide will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.

Also known as: VP-16, VePesid, etopophos, toposar

Polatuzumab vedotin plus R-EPCH

Prednisone DRUG

Prednisone will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. Prednisone will be given orally.

Also known as: Deltasone, Orasone, Paracort, Cortan

Polatuzumab vedotin plus R-EPCH

Cyclophosphamide DRUG

Cyclophosphamide will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.

Also known as: cytoxan

Polatuzumab vedotin plus R-EPCH

Hydroxydaunomycin DRUG

Hydroxydaunomycin will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.

Also known as: Doxorubicin Hydrochloride, Hydroxydoxorubicin Hydrochloride

Polatuzumab vedotin plus R-EPCH

Eligibility Criteria

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

You may qualify if:

• Subject must have confirmed diagnosis of CLL or small lymphocytic lymphoma (SLL) based upon 2018 International Workshop on CLL (IwCLL) criteria, with biopsy proven Richter's Transformation to a DLBCL subtype.
• Subject must be ≥18 years of age.
• Subject must be able to sign informed consent
• Ability and willingness to comply with the study protocol procedures
• Life expectancy of at least 24 weeks
• Subject must have an Eastern Cooperative Oncology Group performance status of ≤2.
• Subject must have measurable disease with atleast on LN\>- 1.5cm in longest diameter
• Subject must have adequate bone marrow function and meet the below thresholds prior to treatment.
• Absolute neutrophil count of ≥1000 cell/uL
• Hemoglobin ≥ 7 g/dL
• Platelet count ≥ 30,000 cells/uL- Subjects may receive growth factor or transfusion support no less than 7 days prior to enrollment or C1 D1.
• Subject must have adequate organ function and meet the thresholds below:
• Total bilirubin ≤ 1.5 times the upper limit of normal (ULN). Subjects with Gilbert's disease will be granted exception to this rule.
• Creatinine clearance \>30 ml/min/1.73m2 as calculated by the MDRD equation.
• Ejection fraction ≥ 50% measured by transthoracic echocardiogram or MUGA scan

You may not qualify if:

• Diagnosis of Richter's Transformation not of DLBCL subtype (including but not limited to Hodgkin lymphoma, PLL)
• Prior therapy targeting Richter's transformation.
• Subject has undergone an allogeneic stem cell transplant for CLL within 6 months of study entry.
• Subject has an active or presumed secondary malignancy at time of enrollment. A subject will be eligible if a previous malignancy was treated with curative intent and there is no evidence of disease recurrence for the past 3 years. Non-melanomatous and cervical squamous cell cancers are an exception and if excised will be allowed to enroll regardless of timing of excision.
• Subject is known to be positive for HIV.
• Active hepatitis C or hepatitis B defined by positive PCRs for viral DNA/RNA. Subjects with a positive Hep B core antibody and negative PCR, are allowed to enroll (prophylaxis is strongly encouraged and monthly monitoring of Hep B PCR is mandatory).
• Subject has baseline ≥ Grade 2 or greater peripheral neuropathy.
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• Clinical evidence or known central nervous system involvement with transformed large cells
• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
• Significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, congestive heart failure, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina)
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization within 4 weeks before Cycle 1 day 1.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Genentech, Inc.: collaborator

Study Sites (4)

Mount Sinai- Icahn School of Medicine

New York, New York, 10029, United States

RECRUITING

Columbia University Medical Center

New York, New York, 10032, United States

RECRUITING

Weill Cornell Medicine

New York, New York, 10065, United States

RECRUITING

Ohio state University

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• WCM Joint Clinical Trials Office

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

polatuzumab vedotin; Rituximab; Etoposide; etoposide phosphate; Prednisone; Cyclophosphamide; Doxorubicin

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides

Study Officials

• John Allan, M.D.

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amelyn Rodriguez, R.N.

CONTACT

2127461362; amr2017@med.cornell.edu

Katherine Greig, R.N.

CONTACT

2127466738; kag9156@med.cornell.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2020
• First Posted: December 22, 2020
• Study Start: September 24, 2021
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: October 7, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)