A Phase 2 Study of Acalabrutinib With DA-EPOCH-R or R-CHOP for Patients With Untreated Diffuse Large B-cell Lymphoma
National Cancer Institute (NCI)
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.
Description
Background: Gene-expression profiling (GEP) has identified two dominant molecular subtypes, activated B cell like (ABC) and germinal center B cell like (GCB), that arise by distinct mechanisms, have distinct prognoses, and respond differently to targeted therapy Recently, genetic subtypes of DLBCL have been described within molecular subtypes that have distinct genotypic, epigenetic, and clinical characteristics providing biologic rationale for precision medicine strategies in DLBCL Frontline treatment of DLBCL is either rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
-INCLUSION CRITERIA: 1. 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…
Interventions
- DrugDA-EPOCH
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.
- BiologicalRituximab
Rituximab 375 mg/m2 IV on Day 1 of each 21-day cycle for 6 cycles.
- DrugCHOP
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.
- DrugAcalabrutinib
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.
Location
- National Institutes of Health Clinical CenterBethesda, Maryland