Acalabrutinib With DA-EPOCH-R or R-CHOP for People With Untreated Diffuse Large B-cell Lymphoma
A Phase 2 Study of Acalabrutinib With DA-EPOCH-R or R-CHOP for Patients With Untreated Diffuse Large B-cell Lymphoma
2 other identifiers
interventional
132
1 country
1
Brief Summary
Background: Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma. Most people with this cancer can be cured. But those who are not cured have a poor prognosis. Researchers want to add another drug to standard treatment see if it can improve the cure rate. Objective: To see if the drug acalabrutinib given with rituximab and standard combination chemotherapy can improve the cure rate of aggressive B-cell lymphomas such as diffuse large B-cell lymphoma. Eligibility: People ages 18 and older with an aggressive B-cell lymphomas that have not been treated Design: Participants will be screened with: Blood and urine tests Physical exam Medical history Tumor biopsy Bone marrow biopsy: A needle will remove marrow from the participant s hipbone. Lumbar puncture: If necessary, a needle will remove fluid from the participant s spinal canal. Imaging scans Participants will take the study drug for up to 14 days. It is a pill taken 2 times a day. Then they will have more scans. They will get rituximab and chemotherapy. They may get these drugs through a needle in an arm vein. Or they may them through a tube placed in a vein in their chest or in their neck. They might also keep taking the study drug. Each treatment cycle lasts 21 days. They will have up to 6 cycles. Participants may have 4 doses of another drug injected into their spinal fluid. Participants will have repeats of the screening tests throughout the study. Participants will have a follow-up visit 30 days after their last treatment, then every 3 months for 2 years, then every 6 months for 3 years, and then yearly.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Aug 2019
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 28, 2019
CompletedFirst Posted
Study publicly available on registry
July 1, 2019
CompletedStudy Start
First participant enrolled
August 5, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 31, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
March 31, 2030
ExpectedJune 3, 2026
February 13, 2026
6.8 years
June 28, 2019
June 2, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Response rate
Number of patients who achieve a CR, PR or SD
every 2 cycles
Secondary Outcomes (5)
Safety and tolerability
initiation of study drug until 30 days after last dose
Progression-free survival
every 3-6 months for 5 years then yearly
Overall survival
every 3-6 months for 5 years then yearly
Event-free survival
every 3-6 months for 5 years then yearly
Complete response rate
6 cycles
Study Arms (1)
1
EXPERIMENTALAcalabrutinib 100 mg orally twice a day for 14 days; Following window: patients with \> or = to 25% tumor reduction, treat with DA-EPOCH-R or R-CHOP + acalabrutinib 100mg orally twice a day for the first 10 days, for 6 cycles; whereas, patients with \<25% tumor reduction, treat with DA-EPOCH-R or R-CHOP alone for 6 cycles
Interventions
Vincristine 1.4 mg/m2 (2 mg cap) IV on Day 1, Doxorubicin 10 mg/m2/day CIVI on Days 1-4, Etoposide 50 mg/m2/day CIVI on Days 1-4, Cyclophosphamide 750 mg/m2 IV on Day 5. Prednisone 60 mg/m2 PO BID is administered daily on Days 1-5 of each cycle. Each cycle is 21 days and drugs will be given for 6 cycles.
Acalabrutinib is administered orally at 100 mg twice a day for 14 days during the window period. During combination therapy, acalabrutinib is administered 100 mg twice daily for the first 10 days for 6 cycles.
Cyclophosphamide 750 mg/m2 IV, Doxorubicin 50 mg/m2 IV, Vincristine 1.4 mg/m2 (2 mg cap) IV are administered on Day 1 of each 21-day cycle for 6 cycles. Prednisone 40 mg/m2 PO is administered daily on Days 1-5 of each cycle.
Eligibility Criteria
You may qualify if:
- Patients must have a confirmed histologic diagnosis of an aggressive B-cell lymphoma with morphologic appearance of DLBCL or high-grade B-cell lymphoma (HGBL) confirmed by the Laboratory of Pathology, NCI, with no prior treatment for DLBCL or HGBL. The following subtypes are included:
- 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
- NOTE: Presence of concomitant indolent lymphomas such as follicular lymphoma, marginal zone lymphomas, monoclonal B-cell lymphocytosis or chronic lymphocytic leukemia/small lymphocytic lymphoma that are best categorized as composite or transformed lymphomas are allowed.
- A formalin-fixed tissue block or 15 slide of tumor sample (archival or fresh) must be available for performance of correlative studies.
- NOTE: Tumor tissue may be from any previously collected tissue and adequacy is at the discretion of the Principal Investigator. Patients must be willing to have a tumor biopsy if adequate archival tissue is not available (i.e., post-enrollment and prior to treatment).
- Measurable lymph nodes or masses of at least 1.5 centimeters (cm) on baseline CT or MRI
- Stage II, III, or IV disease as classified by the Ann Arbor Classification
- +30 more criteria
You may not qualify if:
- Patients who meet histologic criteria for the following subtypes are excluded:
- 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
- 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.
- 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.
- 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
- Requires treatment with moderate or strong CYP3A inhibitors or inducers
- Known lymphomatous involvement of the CNS
- 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
- 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.
- 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.
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Publications (1)
Roschewski M, Kurtz DM, Westin JR, Lynch RC, Gopal AK, Alig SK, Sworder BJ, Cherng HJ, Kuffer C, Blair D, Brown K, Goldstein JS, Schultz A, Close S, Chabon JJ, Diehn M, Wilson WH, Alizadeh AA. Remission Assessment by Circulating Tumor DNA in Large B-Cell Lymphoma. J Clin Oncol. 2025 Dec;43(34):3652-3661. doi: 10.1200/JCO-25-01534. Epub 2025 Aug 13.
PMID: 40802906DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Christopher J Melani, M.D.
National Cancer Institute (NCI)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 28, 2019
First Posted
July 1, 2019
Study Start
August 5, 2019
Primary Completion
May 31, 2026
Study Completion (Estimated)
March 31, 2030
Last Updated
June 3, 2026
Record last verified: 2026-02-13
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Clinical data will be available during the study and indefinitely. @@@@@@Genomic data will be available once genomic data are uploaded per protocol GDS plan for as long as database is active.
- Access Criteria
- Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. @@@@@@Genomic data will be made available via dbGaP through requests to the data custodians.
All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.