Zanubrutinib in Combination With R-PolaCHP (ZaR-PolaCHP) for Newly Diagnosed Diffuse Large B-Cell Lymphoma

NCT04850495 | Suspended Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-20189NCI-2021-01332
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 3

Brief Summary

This phase Ib trial seeks to find out the best dose and possible side effects and/or benefits of zanubrutinib in combination with the R-PolaCHP in treating patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Zanubrutinib is designed to block a protein called Bruton Tyrosine Kinase in order to stop cancer growth. R-CHOP is the acronym for the combination of five drugs: rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. It is the most widely used chemoimmunotherapy regimen for DLBCL and is considered the standard-of-care treatment for patients with DLBCL. Three of the drugs in R-CHOP (cyclophosphamide, doxorubicin and vincristine) are chemotherapy drugs. Rituximab is a type of immunotherapy and prednisone is a type of steroids.

Conditions

Diffuse Large B-Cell Lymphoma; Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma; Transformed Marginal Zone Lymphoma to Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events

  Measured by the Common Terminology Criteria for Adverse Events version 5.0.

  Up to 24 months

Secondary Outcomes (10)

• Objective response rate (ORR)

  Up to 5 years

• Progression-free survival

  From the start of treatment to time of progression or death, whichever occurs first, assessed up to 5 years

• Overall survival (OS)

  From start of treatment to death from any cause, assessed up to 5 years

• Zanubrutinib duration of treatment

  Up to 6 cycles (each cycle is 21 days in length)

• Zanubrutinib average daily dose

  Up to 6 cycles (each cycle is 21 days in length)

Study Arms (1)

Treatment (zanubrutinib, R-CHOP)

EXPERIMENTAL

Patients receive zanubrutinib PO on days 1-21, rituximab IV on day 1, cyclophosphamide IV on day 1, doxorubicin hydrochloride IV on day 1, vincristine sulfate IV on day 1, and prednisone PO QD on days 1-5. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Drug: Prednisone; Biological: Rituximab; Drug: Vincristine Sulfate; Drug: Zanubrutinib

Interventions

Rituximab BIOLOGICAL

Given IV

Also known as: 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, PF-05280586, Rituxan, Rituximab ABBS, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, Rituximab Biosimilar SIBP-02, rituximab biosimilar TQB2303, rituximab-abbs, RTXM83, Truxima

Treatment (zanubrutinib, R-CHOP)

Vincristine Sulfate DRUG

Given IV

Also known as: Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfate

Treatment (zanubrutinib, R-CHOP)

Zanubrutinib DRUG

Given PO

Also known as: BGB-3111, Brukinsa, BTK-InhB

Treatment (zanubrutinib, R-CHOP)

Prednisone DRUG

Given PO

Also known as: .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, Perrigo Prednisone, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisone Intensol, Prednisonum, Prednitone, Promifen, Rayos, Servisone, SK-Prednisone

Treatment (zanubrutinib, R-CHOP)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (zanubrutinib, R-CHOP)

Doxorubicin Hydrochloride DRUG

Given IV

Also known as: 5,12-Naphthacenedione, 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-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin HCl, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, hydroxydaunorubicin, Rubex

Treatment (zanubrutinib, R-CHOP)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed DLBCL, irrespective of cell-of-origin. Patients with previously diagnosed indolent lymphoma (follicular lymphoma and marginal zone lymphoma but not small lymphocytic lymphoma) who have transformed to DLBCL are eligible only if they have not previously been treated for indolent lymphoma except for local radiation for early-stage disease
• Patients may have received brief treatment with glucocorticoids (up to 250 mg/day prednisone or equivalent for a maximum of 10 days) and/or 1 cycle of chemotherapy such as R-CHOP (or some component\[s\] thereof) for the diagnosis of B-cell lymphoma provided they had staging computed tomography (CT) and/or positron emission tomography (PET)/CT scans prior to chemotherapy. Treatment must occur within 28 days prior to enrollment
• Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of zanubrutinib in combination with R-CHOP in patients \<18 years of age, children are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2. Performance status of 3 will be accepted if the impairment is caused by DLBCL complications and improvement is expected once therapy is initiated
• Measurable disease (defined as \>= 1.5cm in diameter) or at least one PET fludeoxyglucose F-18 (FDG) avid area of disease
• Patients must have adequate hematologic, hepatic, and renal function as defined below:
• Hemoglobin \>= 7.0 g/dL
• Absolute neutrophil count (ANC) \> 1,000/mcL
• Platelet count \> 75,000/mcL
• Total bilirubin =\< 1.5 x the upper limit of the normal range (ULN) (unless due to Gilbert's disease)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) \< 2.5 x institutional ULN
• Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) \< 2.5 x institutional ULN
• Creatinine clearance \> 40 mL/min calculated by Cockcroft-Gault
• Adequate cardiac function with a left ventricular ejection fraction (LVEF) \>= 50% as assessed by echocardiogram or MUGA (Multigated acquisition scan)
• The effects of zanubrutinib on the developing human fetus are unknown. For this reason and because chemotherapeutic agents used in this study are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (double barrier method of birth control or abstinence) 2 weeks prior to initiation of treatment, for the duration of study participation and for 3 months after completing treatment. Should a woman become pregnant or suspect that she is pregnant while she or her partner is participating in this study, she should inform the treating physician immediately. Men must agree to refrain from sperm donation for at least 90 days after the last dose of zanubrutinib

You may not qualify if:

• Major surgery within 4 weeks before Day 1, Cycle 1 of treatment
• Prior anthracycline use \>= 150 mg/m\^2
• Known central nervous system (CNS) involvement. Patients at high risk for secondary CNS involvement but without neurologic symptoms suspected to be due to lymphoma are allowed to be enrolled and receive intrathecal chemotherapy with methotrexate, cytarabine, and/or glucocorticoids. Concurrent (during treatment with ZaR-polaCHP) CNS prophylaxis with IV methotrexate is NOT permitted in this study. CNS prophylaxis with IV methotrexate after completing ZaR-PolaCHP treatment and obtaining end-of-treatment response assessment is allowed. Patients who are enrolled and subsequently identified to have pathologic confirmation of CNS involvement by lymphoma may be continued on the study at the discretion of the principal investigator
• Active systemic bacterial, fungal or viral infection except for localized fungal infections of skin or nails. Patients with resolving infections such as urinary tract, respiratory, or skin infections may be enrolled if clinically improving. NOTE: patients may be receiving prophylactic antiviral or antibacterial therapies at the investigator's discretion
• Evidence of current uncontrolled or symptomatic cardiovascular conditions, including, uncontrolled cardiac arrhythmias, history of or symptomatic congestive heart failure (New York Heart Association \[NYHA\] Class III or greater), unstable angina, or myocardial infarction within the past 6 months. Poorly controlled or clinically significant atherosclerotic vascular disease including angioplasty, cardiac or vascular stenting within 6 months of enrollment
• History of cerebrovascular accident or transient ischemic attack within the 6 months before Day 1, Cycle 1 of treatment
• Any prior history of intracranial hemorrhage
• Known bleeding diatheses or platelet dysfunction disorders
• Known gastrointestinal (GI) disease or gastrointestinal procedure that will significantly interfere with the oral absorption or tolerance of zanubrutinib including the inability to swallow pills/capsules
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
• Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
• Evidence of prior malignancy except for: adequately treated non-melanoma skin cancer, adequately treated in situ carcinoma, low-grade prostate carcinoma (Gleason grade =\< 6) managed with observation that has been stable for at least 6 months, or any malignancy treated with curative intent and continuously disease-free for at least 3 years
• Participation in other interventional clinical trials, including those with other investigational agents not included in this trial, within 21 days of Day 1, Cycle 1 of this trial. Also excluded are patients who are receiving any other investigational agents outside of a clinical trial
• Known history of human immunodeficiency virus (HIV), active hepatitis C infection (HCV ribonucleic acid \[RNA\] polymerase chain reaction \[PCR\]-positive) and/or active hepatitis B infections (HBV deoxyribonucleic acid \[DNA\] PCR-positive). If hepatitis B virus core (HBc) antibody is positive, the patient must be evaluated for the presence of HBV DNA by PCR. If HCV antibody is positive, the patient must be evaluated for the presence of HCV RNA by PCR. Patients with positive HBc antibody and negative HBV DNA by PCR are eligible. Patients with positive HCV antibody and negative HCV RNA by PCR are eligible
• Pregnant or breastfeeding women are excluded from this study. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with zanubrutinib, breastfeeding should be discontinued if the mother is treated with zanubrutinib. These potential risks may also apply to other agents used in this study

Sponsors & Collaborators

• Yazeed Sawalha: lead

Study Sites (3)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

MUSC

Charleston, South Carolina, 29425, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Cyclophosphamide; Doxorubicin; Prednisone; deltacortene; prednylidene; Rituximab; CT-P10; Vincristine; zanubrutinib

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)

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; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Yazeed Sawalha, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 14, 2021
• First Posted: April 20, 2021
• Study Start: November 16, 2021
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): December 15, 2026
• Last Updated: June 4, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)