AzTrials
AzTrials

Diffuse Large B-Cell LymphomaPhase 1NCT04850495

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

A Phase 1 study testing Cyclophosphamide, Doxorubicin Hydrochloride and Prednisone in people with Diffuse Large B-Cell Lymphoma and Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma, run by Yazeed Sawalha at 3 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cyclophosphamide, Doxorubicin Hydrochloride and Prednisone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
3 sitesUnited States
Study dates
16 Nov 2021to 15 Dec 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 24Show fewer
  • 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
  • Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) or urine pregnancy test at screening. Women who are pregnant or breastfeeding are ineligible for this study
  • Patients must have the ability to understand and the willingness to sign a written informed consent document and Health Insurance Portability and Accountability Act (HIPAA) consent document. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care
  • International Prognostic Index must be documented:
  • ECOG performance status >= 2 (1 point)
  • Age >= 60 (1 point)
  • >= 2 extranodal sites (1 point)
  • Lactate dehydrogenase measurement (LDH) > upper limit of normal (1 point)
  • Ann Arbor Stage III or IV (1 point)
  • Is there evidence of transformation from indolent lymphoma?

Who cannot join

  • 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
Show all 15Show fewer
  • 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

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • MUSC

    Charleston, South Carolina, 29425

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: A Phase Ib Trial of Zanubrutinib in Combination With R-PolaCHP (ZaR-PolaCHP) for Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Determine the safety, toxicity profile and recommended phase 2 dose (RP2D) of zanubrutinib in combination with ZaR-PolaCHP (ZaR-PolaCHP) for patients with previously untreated diffuse large B-cell lymphoma (DLBCL).

SECONDARY OBJECTIVES:

  1. Determine the objective response rate (ORR) (complete and partial responses), progression-free survival (PFS) and overall survival (OS) of ZaR-CHOP in patients treated at the RP2D.

II. Provide descriptive data on treatment exposure to zanubrutinib and R-CHOP including treatment discontinuation rate and relative dose intensity.

EXPLORATORY OBJECTIVES:

  1. Examine archival tumor samples attained before starting treatment on trial to determine the clinical outcomes of molecularly defined DLBCL subtypes in patients treated with ZaR-Pola-CHP or ZaR-CHOP.

II. Measure circulating tumor deoxyribonucleic acid (DNA) (ctDNA) to correlate its presence with response by positron emission tomography (PET) imaging.

OUTLINE: This is a dose de-escalation study of zanubrutinib and fixed-dose R-CHOP regimen followed by a dose-expansion study.

Patients receive zanubrutinib orally (PO) once or twice daily on days 1-21, rituximab intravenously (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.

After completion of study treatment, patients are followed every 6 months for 2 years.

Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • Doxorubicin HydrochlorideDrug

    Also called 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

    Given IV

  • PrednisoneDrug

    Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl

    Given PO

  • RituximabBiological

    Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody

    Given IV

  • Vincristine SulfateDrug

    Also called Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin

    Given IV

  • ZanubrutinibDrug

    Also called BGB-3111, Brukinsa, BTK-InhB

    Given PO

Study groups in NCT04850495
Study groupRoleWhat they receive
Treatment (zanubrutinib, R-CHOP)ExperimentalPatients 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.
Receives: Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Drug: Prednisone; Biological: Rituximab; Drug: Vincristine Sulfate; Drug: Zanubrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of adverse events

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

    Measured: Up to 24 months

Secondary outcomes (10)

  1. Objective response rate (ORR)

    Defined as the proportion of patients achieving a complete or partial response. ORR will be reported with a 95% binomial confidence interval.

    Measured: Up to 5 years

  2. Progression-free survival

    Will be estimated using the method of Kaplan-Meier, where the estimates at time points of interest will be reported with 95% confidence intervals.

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

  3. Overall survival (OS)

    Will be estimated using the method of Kaplan-Meier, where the estimates at time points of interest will be reported with 95% confidence intervals.

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

  4. Zanubrutinib duration of treatment

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

  5. Zanubrutinib average daily dose

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

  6. Zanubrutinib discontinuation rate

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

  7. Zanubrutinib relative dose intensity

    Defined as the ratio of the amount of a drug actually administered to the amount planned for a fixed time period.

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

  8. Number of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP) cycles received

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

  9. R-CHOP discontinuation rates

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

  10. R-CHOP relative dose intensity

    Defined as the ratio of the amount of a drug actually administered to the amount planned for a fixed time period.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Apr 2021
  2. Study start16 Nov 2021
  3. Primary completion23 Jun 2026
  4. Study completion15 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04850495
Sponsor's protocol ID
OSU-20189
Other IDs
NCI-2021-01332
Status last verified
Jun 2026
First submitted
14 Apr 2021
Last updated
2 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cyclophosphamide, Doxorubicin Hydrochloride and Prednisone in people with Diffuse Large B-Cell Lymphoma and Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma, run by Yazeed Sawalha at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 2 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (time frame: Up to 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04850495.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in