Acalabrutinib with Chemotherapy for Untreated Diffuse Large B-cell Lymphoma
This study is looking at whether adding acalabrutinib to standard chemotherapy treatments (DA-EPOCH-R or R-CHOP) can improve the cure rate for people with untreated diffuse large B-cell lymphoma (DLBCL), a common type of non-Hodgkin's lymphoma. Acalabrutinib works by targeting a specific pathway in cancer cells. Researchers will measure how many participants respond to the treatment to see if it's successful. You may be eligible if you are 18 or older and have not received prior treatment for aggressive B-cell lymphoma, including DLBCL. The study aims to enroll 132 participants.
- Study design
- This interventional study is designed to enroll 132 participants. It is not specified if it is randomized or blinded.
- What's involved
- You will undergo blood and urine tests, a physical exam, medical history review, a tumor biopsy, and a bone marrow biopsy. Acalabrutinib is taken orally twice a day for 14 days initially, then for the first 10 days of each of 6 cycles during combination therapy.
- Compensation
- Not stated in the trial record.
- Follow-up
- Your response to treatment will be measured every 2 cycles.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT04002947
Acalabrutinib With DA-EPOCH-R or R-CHOP for People With Untreated Diffuse Large B-cell Lymphoma
Recruiting
PHASE2Ages 18+InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~132 participants
Updated 2026-09-11 on ClinicalTrials.gov
What's tested:DA-EPOCHRituximabCHOPAcalabrutinib
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Response rate
Measured over every 2 cycles
Conditions
NCT04002947
Where you'd take part
This study runs at 1 site. They're the same protocol — you choose where, and that choice sets who your contact draft is addressed to.
National Institutes of Health Clinical Center
Bethesda, Marylandstudy coordinator listed
Recruiting
Sites open and close at different times, so the status above is per site — it can differ from the study's overall status.
Study leadership
- Christopher J Melani, M.D. · PRINCIPAL_INVESTIGATOR · National Cancer Institute (NCI)
Who to contact
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Eligibility criteria
Inclusion
DLBCL, NOS, Activated B-cell type (ABC)
DLBCL, NOS, Germinal center B-cell type (GCB)
T-cell/histiocyte-rich large B-cell lymphoma
Primary cutaneous DLBCL, leg-type
EBV+ DLBCL, NOS
DLBCL associated with chronic inflammation
ALK+ large B-cell lymphoma
High-grade B-cell lymphoma, NOS
High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
absolute neutrophil count\* \>=1,000/mcL
hemoglobin\* \>= 8 g/dL (transfusions permitted to meet criteria)
Platelets \>= 75,000/mcL (transfusions not permitted)
total bilirubin \<= 1.5 X institutional ULN (or \<= 3 X institutional ULN for patients with documented Gilberts syndrome or cholestatic obstruction or involvement by lymphoma)
AST(SGOT)/ALT(SGPT) \<= 3 X institutional ULN (\<= 5 x ULN for patients with cholestatic obstruction or involvement by lymphoma
Serum creatinine \<= 2.0 mg/dL
Creatinine clearance \>=40 mL/min/1.73 m2 for patients with creatinine levels above 2 mg/dL
Individuals of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrollment.
Individuals of childbearing potential who are sexually active must agree to highly effective contraception prior to study entry, for the duration of study participation, and for at least 2 days after the last dose of acalabrutinib or 12 months after the last dose of combined chemotherapy, whichever is later. Individuals who can father children must use highly effective contraception prior to study entry, for the duration of study participation, and for 12 months after the last dose of combined chemotherapy; there is no contraception timing requirement post-last dose of acalabrutinib alone if an individual who can father children does not initiate chemotherapy on study after the acalabrutinib window.
Participants must not be planning to conceive or father children within the projected duration of the trial, starting with the pre-screening/screening visit through 2 days after the last dose of acalabrutinib or 12 months after the last dose of combined chemotherapy, whichever is later.
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, which may be oral, intravaginal, or transdermal
Progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injectable, or implantable
Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)
Bilateral tubal occlusion
Vasectomy of participant or participant's partner (with medical assessment and confirmation of vasectomy surgical success)
Sexual abstinence (only if refraining from heterosexual intercourse during the entire period of risk associated with the study treatments)
Exclusion
Primary DLBCL of the central nervous system (PCNSL)
Primary mediastinal B-cell lymphoma (PMBL)
Plasmablastic lymphoma
Intravascular large B-cell lymphoma
B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma 2. Patients who, at the discretion of the investigator, need immediate cytoreductive chemotherapy such as patients with evidence of spontaneous tumor lysis or impending organ compromise are not eligible. 3. Current or prior anti-cancer treatment for DLBCL prior to enrollment. Short course of corticosteroids (\<7 days) for acute issues prior to study enrollment are permitted. 4. Major surgical procedure within 30 days of first dose of study drug. If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug 5. Requires treatment with moderate or strong CYP3A inhibitors or inducers 6. Known lymphomatous involvement of the CNS 7. Pregnant individuals, or individuals who intend to become pregnant during the study are excluded from this study because of potential teratogenic effects associated with acalabrutinib, R-CHOP, and/or DA-EPOCH-R 8. The potential for all study treatments to be excreted in the milk of nursing mothers is unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with acalabrutinib, nursing must be discontinued. 9. Uncontrolled intercurrent illness including, but not limited to the following that may limit interpretation of results or that could increase risk to the patient at the discretion of the investigator:
Other malignancy that requires ongoing systemic hormonal therapy, chemotherapy, or immunotherapy.
Any condition that requires anticoagulation with warfarin or equivalent vitamin K antagonist
Active bleeding, history of bleeding diathesis (e.g., hemophilia or von Willebrand disease)
Suspected or confirmed Progressive Multifocal Leukoencephalopathy (PML)
Active hepatitis C infection. NOTE: Subjects who are hepatitis C antibody positive will need to have a negative HCV PCR result before enrollment. Those with a positive PCR for hepatitis C are excluded.
Active hepatitis B infection. NOTE: Patients who are hepatitis B surface antigen (HbsAg) positive will be excluded from enrollment. Patients who are hepatitis B core antibody (HbcAb) positive will need to have a negative HBV PCR result before enrollment. Those with a positive PCR for hepatitis B are excluded. Those who are hepatitis B core antibody (HbcAb) positive with a negative PCR for hepatitis B will be treated with antivirals designed to prevent hepatitis B reactivation (e.g., entecavir) throughout therapy and for 12 months after therapy and have monitoring for hepatitis B reactivation with PCR.
History of hemorrhagic stroke or intracranial hemorrhage in preceding 6 months
Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification. Subjects with controlled atrial fibrillation/flutter during screening are eligible.
Uncontrolled autoimmune hemolytic anemia
Inability to swallow oral medications, or disease involve that significantly limits absorption of oral medication
Known mental or physical illness that would interfere with cooperation with the requirements of the trial or confound the results or interpretation of the results of the trial and, in the opinion of the treating investigator, would make the patient inappropriate for entry into the study. 10. Concurrent participation in another therapeutic clinical trial.
What this trial measures
- Response rateevery 2 cycles
Number of patients who achieve a CR, PR or SD