Polatuzumab Vedotin and Combination Chemotherapy for the Treatment of Previously Untreated Lymphoma

NCT04479267 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2019-135P30CA022453
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well polatuzumab vedotin and combination chemotherapy work in treating patients with previously untreated double, triple hit lymphoma, Double Expressor Lymphoma or High-Grade B Cell Lymphoma. Polatuzumab vedotin is a monoclonal antibody that works by binding with cancer cells and releasing another chemotherapy drug, called monomethyl auristatin E, into the cell causing the cancer cells to die or stop growing. Chemotherapy drugs, such as rituximab, cyclophosphamide, doxorubicin, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving polatuzumab vedotin with combination chemotherapy may work better in treating patients with double or triple hit lymphoma compared to combination chemotherapy alone.

Conditions

Diffuse Large B-Cell Lymphoma; High Grade B-Cell Lymphoma w/MYC & BCL2 or BCL6 Rearrangements; High Grade B-Cell Lymphoma w/MYC, BCL2 & BCL6 Rearrangements; Double Expressor Lymphoma; High-grade B-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Rate of complete remission

  Will be assessed by modified Lugano response criteria for malignant lymphoma. The complete remission rate will be summarized by a binomial response rate and its associated 2-sided 80% confidence interval (CI) using Pearson-Klopper method. The primary efficacy analysis will be also performed based on all response evaluable subjects as a sensitivity analysis.

  Up to 6-8 weeks after cycle 6 day 1 (cycles = 21 days) or last dose of study medication

Secondary Outcomes (4)

• Incidence of adverse events

  Up to 30 days after last dose of study treatment

• Progression-free survival (PFS)

  From the start date of the treatment until the date of progression or death from any cause, whichever occurs first, assessed up to 12 months

• Overall response rate (ORR)

  Up to 12 months

• Duration of response (DOR)

  From the date of CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is documented among all treated subjects who had a confirmed CR or PR, assessed up to 12 months

Other Outcomes (1)

• Biomarker assessment

  Up to time of disease progression, assessed up to 12 months

Study Arms (1)

Treatment (polatuzumab vedotin, R-CHP)

EXPERIMENTAL

Patients receive prednisone PO, prednisolone IV, or methylprednisolone IV on days 1-5. Patients also receive rituximab IV, polatuzumab vedotin IV over 30-90 minutes, cyclophosphamide IV, and doxorubicin hydrochloride IV on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Prednisone; Drug: Prednisolone; Drug: Methylprednisolone; Biological: Rituximab; Drug: Polatuzumab Vedotin; Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride

Interventions

Prednisone DRUG

Given PO

Also known as: .delta.1-Cortisone, 1, 2-Dehydrocortisone, 17,21-Dihydroxypregna-1,4-diene-3,11,20-trione, 53-03-2, Adasone, Cortancyl, Dacortin, , Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome

Treatment (polatuzumab vedotin, R-CHP)

Prednisolone DRUG

Given IV

Also known as: (11beta)-11,17,21-Trihydroxypregna-1,4-diene-3,20-dione, .delta.1-Hydrocortisone, 1,2-Dehydrohydrocortisone, 50-24-8, 9120, Adnisolone, Aprednislon, Capsoid, Cortalone, Cortisolone

Treatment (polatuzumab vedotin, R-CHP)

Methylprednisolone DRUG

Given IV

Also known as: (6alpha,11beta)-11,17,21-Trihydroxy-6-methylpregna-1,4-diene-3,20-dione, 6Alpha-Methylprednisolone, Adlone, Caberdelta M, DepMedalone, Depo Moderin, Depo-Nisolone, Duralone, Emmetipi, Esametone

Treatment (polatuzumab vedotin, R-CHP)

Rituximab BIOLOGICAL

Given IV

Also known as: 174722-31-7, 687451, ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8

Treatment (polatuzumab vedotin, R-CHP)

Polatuzumab Vedotin DRUG

Given IV

Also known as: 1313206-42-6, ADC DCDS4501A, Antibody-Drug Conjugate DCDS4501A, DCDS4501A, FCU 2711, POLATUZUMAB VEDOTIN, polatuzumab vedotin-piiq, Polivy, RG7596, Ro 5541077-000

Treatment (polatuzumab vedotin, R-CHP)

Cyclophosphamide DRUG

Given IV

Also known as: 1-bis(2-chloroethyl)-amino-1-oxo-2-aza-5-oxaphosphoridin monohydrate, 2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate

Treatment (polatuzumab vedotin, R-CHP)

Doxorubicin Hydrochloride DRUG

Given IV

Also known as: 14-Hydroxydaunorubicin Hydrochloride, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-

Treatment (polatuzumab vedotin, R-CHP)

Eligibility Criteria

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

You may qualify if:

• Signed informed consent form (ICF)
• Previously untreated patients (except for one prior cycle of CHOP+R) with diffuse large B-cell lymphoma (DLBCL) as determined by local pathology. World Health Organization (WHO) histologies will include:
• Double hit lymphoma (DHL) or triple hit lymphoma (THL) confirmed by fluorescence in situ hybridization (FISH) testing by local pathology (defined as MYC and BCL2 and/or BCL6 rearrangements)
• High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements
• Double expressor lymphoma (DEL) defined as overexpression of MYC(\> or = to 40%) and BCL2 (\> or = to 50%) identified by immunohistochemistry (IHC)
• High grade B-cell lymphoma (HGBL) NOS subtype
• Availability of archival formalin-fixed paraffin-embedded (FFPE) tissue blocks or 15 unstained slides serial sections (3-5 um in thickness) prior to study enrollment. The pathology report must be available for review and a tissue block sent for retrospective central confirmation of diagnosis. If central confirmation is unable to be performed on submitted material, stained slides used for diagnosis and/or additional tumor tissue specimens may also be requested
• \* For clarification: Only availability of tumor sample must be verified prior to C1D1 however treatment can commence prior to completion of central review. The adequacy of the tissue will be confirmed if possible (ie. if it will not delay treatment).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Life expectancy of at least 24 weeks
• At least one bi-dimensionally measurable lesion \> 1.5 cm in its longest dimension as measured by CT or magnetic resonance imaging (MRI)
• Ability and willingness to comply with the study protocol procedures
• Left ventricular ejection fraction (LVEF) \>= 45% on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)
• Hemoglobin \>= 8.0 g/dL without packed RBC transfusion during 14 days before first treatment (unless due to underlying disease, as established by extensive bone marrow involvement or due to hypersplenism secondary to the involvement of the spleen by DLBCL per the investigator)
• Absolute neutrophil count (ANC) \>= 1,000/uL (unless due to underlying disease, as established by extensive bone marrow involvement or due to hypersplenism secondary to the involvement of the spleen by DLBCL per the investigator)

You may not qualify if:

• Contraindication to any of the individual components of R-cyclophosphamide, doxorubicin hydrochloride, oxaliplatin, prednisone (CHOP) or any component of PoV, including prior receipt of anthracyclines or history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (MAbs) (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products
• Contraindication to rituximab or prior administration of an anti CD 20 antibody
• Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer prior to cycle 1 day 1 with the following exceptions:
• One prior treatment cycle of CHOP+R is allowed. Patients who received one prior R-CHOP will receive 6 cycles of R-CHP plus Polatuzumab Vedotin per protocol treatment.
• Glucocorticoid treatment required for lymphoma symptom control prior to the start of study treatment, prednisone 100 mg or equivalent can be given for a maximum of 13 days as a prephase treatment, with all tumor assessments completed prior to starting prednisone
• One dose of prophylactic intrathecal chemotherapy with methotrexate
• Grade 3b follicular lymphoma
• Primary mediastinal (thymic) large B-cell lymphoma
• Burkitt lymphoma
• Primary or secondary central nervous system (CNS) lymphoma (primary or secondary involvement), primary effusion DLBCL, and primary cutaneous DLBCL
• Current grade 2 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE) 5.0
• History of other malignancy that could affect compliance with the protocol or interpretation of results. Exceptions include, but are not limited to:
• Patients with a history of curatively treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or ductal carcinoma in situ of the breast at any time prior to the study are eligible
• A patient with any other malignancy that has been treated with surgery alone with curative intent and the malignancy has been in remission without treatment for \>= 3 years prior to enrollment is eligible
• Patients with low-grade, early-stage prostate cancer with no requirement for therapy at any time prior to study are eligible

Sponsors & Collaborators

• Barbara Ann Karmanos Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Prednisone; Prednisolone; Methylprednisolone; exifone; Rituximab; CT-P10; polatuzumab vedotin; Cyclophosphamide; Doxorubicin

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Dipenkumar Modi, M.D.

  Barbara Ann Karmanos Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 16, 2020
• First Posted: July 21, 2020
• Study Start: August 21, 2020
• Primary Completion: June 19, 2025
• Study Completion (Estimated): July 19, 2026
• Last Updated: September 29, 2025

Record last verified: 2025-09

Locations

US (1)