Testing CC-486 (Oral Azacitidine) Plus the Standard Drug Therapy in Patients 75 Years or Older With Newly Diagnosed Diffuse Large B Cell Lymphoma
Ann Arbor Stage III Diffuse Large B-Cell Lymphoma, Ann Arbor Stage IIX (Bulky) Diffuse Large B-Cell Lymphoma, Ann Arbor Stage IV Diffuse Large B-Cell Lymphoma
About this trial
This is an interventional treatment trial for Ann Arbor Stage III Diffuse Large B-Cell Lymphoma
Eligibility Criteria
Inclusion Criteria:
- Participants must have histologically or cytologically confirmed diffuse large B-cell lymphoma (DLBCL), Ann Arbor Stage IIX (bulky), III or IV. Participants with DLBCL transformed from follicular lymphoma (FL) or marginal zone lymphoma (MZL, including mucosa-associated lymphoid tissue [MALT] lymphomas), lymphoplasmacytic lymphoma (LPL), or nodular lymphocyte-predominant Hodgkin Lymphoma (NLPHL) are eligible. Participants with Grade IIIB follicular lymphoma (FL) or high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements are also eligible. Participants with DLBCL that arose from prior CLL (Richter's transformation) are not eligible.
As defined by the World Health Organization (WHO), eligible lymphoma subtypes include the following:
- DLBCL, not otherwise specified (NOS)
- DLBCL, germinal-center B-cell type (GCB)
- DLBCL, activated B-cell type (ABC)
- T-cell histiocyte-rich B-cell lymphomas (THRBCL)
- Primary cutaneous DLBCL, leg type
- Intravascular large B cell lymphoma
- EBV+ DLBCL, NOS
- DLBCL associated with chronic inflammation
- HHV8+ DLBCL, NOS
- High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements
- High grade B-cell lymphoma, NOS
- Follicular lymphoma grade 3b
- Participants must have staging imaging performed within 28 days prior to registration, as follows. Positron emission tomography (PET)-computed tomography (CT) baseline scans are strongly preferred; diagnostic quality magnetic resonance imaging (MRI), contrast-enhanced CT, or contrast-enhanced MRI scans are also acceptable if PET-CT is not feasible at baseline. Note: PET-CT will be required at end of treatment (EOT) and progression for response assessment. All measurable lesions (longest diameter >= 1.5 cm) must be assessed within 28 days prior to registration. Tests to assess non-measurable disease must be performed within 42 days prior to registration.
- Participants with known human immunodeficiency virus (HIV)-infection are eligible providing they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test (must be within 26 weeks prior to registration). Participants with known HIV must have a CD4 count checked within 28 days prior to registration, but may proceed with therapy regardless of CD4 count.
- All participants must be screened for chronic hepatitis B virus (HBV) within 28 days prior to registration. Participants with known HBV infection (positive serology) must also have a HBV viral load performed within 28 days prior to registration, and participants must have an undetectable HBV viral load on suppressive therapy within 28 days prior to registration. Participants found to be HBV carriers during screening are eligible and must receive standard of care prophylaxis. Participants with active hepatitis B (HBV viral load > 500 IU/mL) within 28 days prior to registration are not eligible
- Participants with a known history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load within in 28 days prior to registration
- Participants must have a Zubrod performance status of 0-2
- Participants must have adequate renal function, as demonstrated by a creatinine clearance, calculated by the Cockcroft and Gault formula, of >= 30 ml/min that was obtained within 28 days prior to registration
- Aspartate aminotransferase (AST) =< 2.5 x institutional upper limit of normal (IULN), alanine aminotransferase (ALT) =< 2.5 x IULN (within 28 days prior to registration)
- Total bilirubin =< 2 x institutional upper limit of normal (IULN), unless due to Gilbert's disease, hemolysis, or lymphomatous involvement of liver (within 28 days prior to registration). Note: If total bilirubin is elevated, and direct bilirubin is subsequently performed (within 28 days prior to registration) and resulted to be =< 2 x IULN, the participant will be considered eligible
- Absolute neutrophil count (ANC) >= 1000/mcL (within 28 days prior to registration)
- Platelets >= 75,000/mcL (within 28 days prior to registration)
- Hemoglobin (Hgb) >= 8 g/ dL (within 28 days prior to registration)
If there is a documented lymphomatous involvement of the bone marrow, bone marrow function within 28 days prior to registration, as evidenced by:
- ANC >= 500/mcL
- Platelets >= 50,000/mcL
- Hemoglobin (Hgb) >= 8 g/ dL
- Participants must have a left ventricular ejection (LVEF) fraction >= 45% as measured by echocardiogram or radionuclide (multigated acquisition scan [MUGA]) ventriculography within 56 days prior to registration
For the duration of the study treatment period and for at least 4 months following the last dose of study drug, male participants must agree to use effective contraceptive methods during sexual contact with a female of childbearing potential (FCBP) and must agree to refrain from semen or sperm donation during the same timeframe. Effective contraceptive methods include a history of vasectomy, use of hormonal contraception or an intrauterine device (IUD) by the female partner, or use of condoms
- A FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
Exclusion Criteria:
- Participants must not have known lymphomatous involvement of the central nervous system (CNS)
- Participants must not have active inflammatory bowel disease (such as, Crohn's disease, ulcerative colitis), celiac disease (i.e., sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption, distribution, metabolism, or excretion of the study drug and/or predispose the subject to an increased risk of gastrointestinal toxicity
- Participants must not have received any prior cytotoxic chemotherapy or rituximab for treatment of the newly diagnosed DLBCL except for the pre-phase treatment (within specified dose range) that may have either started before or may start after registration to S1918. Inhaled, nasal, and topical steroid use is allowed. Prior cytotoxic chemotherapy and/or antibody therapy for an indolent lymphoma prior to transformation is allowed. Up to 4 doses of intrathecal (IT) chemotherapy administered for central nervous system (CNS) prophylaxis is allowed in addition to protocol therapy. High-dose intravenous methotrexate is not allowed.
- Participants must not have received more than a cumulative of dose 250 mg/m^2 of prior doxorubicin (or equivalent dose of another anthracycline, such as epirubicin) therapy (at any time prior to registration).
- Participants must not currently be receiving any other investigational agents
- Participant must not have a history of allergic reactions attributed to azacitidine, mannitol, or other hypomethylating agents
- Participants must not have active infection (systemic fungal, bacterial, or viral infection) that is not controlled (defined as ongoing signs/symptoms related the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment)
- Participants must not have active cardiac disease within 26 weeks prior to registration, including: symptomatic congestive heart failure (New York Heart Association [NYHA] class 4), unstable angina pectoris, hemodynamically unstable cardiac arrhythmia, or myocardial infarction
- Participants must not have >= grade 2 neuropathy, by Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0, within 28 days prior to registration
- Participants must not have any other known uncontrolled intercurrent illness including, but not limited to ongoing psychiatric illness/social situations that would limit compliance with study requirements
Sites / Locations
- Banner University Medical Center - Tucson
- University of Arizona Cancer Center-North Campus
- University of Arkansas for Medical SciencesRecruiting
- Kaiser Permanente-AnaheimRecruiting
- Kaiser Permanente-Baldwin ParkRecruiting
- Kaiser Permanente-BellflowerRecruiting
- Tower Cancer Research FoundationRecruiting
- UC Irvine Health Cancer Center-Newport
- City of Hope Comprehensive Cancer CenterRecruiting
- Kaiser Permanente-FontanaRecruiting
- Kaiser Permanente - Harbor CityRecruiting
- City of Hope at Huntington BeachRecruiting
- City of Hope at Irvine LennarRecruiting
- Kaiser Permanente-IrvineRecruiting
- City of Hope Antelope ValleyRecruiting
- City of Hope at Long Beach ElmRecruiting
- Kaiser Permanente Los Angeles Medical CenterRecruiting
- Kaiser Permanente West Los AngelesRecruiting
- Cedars Sinai Medical CenterRecruiting
- City of Hope Newport BeachRecruiting
- Kaiser Permanente-OntarioRecruiting
- UC Irvine Health/Chao Family Comprehensive Cancer CenterRecruiting
- Stanford Cancer Institute Palo AltoRecruiting
- Kaiser Permanente - Panorama CityRecruiting
- Kaiser Permanente-RiversideRecruiting
- Kaiser Permanente-San Diego ZionRecruiting
- Kaiser Permanente-San MarcosRecruiting
- UCSF Cancer Center - San MateoRecruiting
- City of Hope UplandRecruiting
- Kaiser Permanente-Woodland HillsRecruiting
- SCL Health Cancer Centers of Colorado - Lutheran Medical CenterRecruiting
- Delaware Clinical and Laboratory Physicians PARecruiting
- Helen F Graham Cancer CenterRecruiting
- Medical Oncology Hematology Consultants PARecruiting
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- Emory University Hospital/Winship Cancer InstituteRecruiting
- Emory Saint Joseph's HospitalRecruiting
- Augusta University Medical CenterRecruiting
- Hawaii Cancer Care - WestridgeRecruiting
- Pali Momi Medical CenterRecruiting
- Hawaii Cancer Care Inc - Waterfront PlazaRecruiting
- Queen's Cancer Cenrer - POB IRecruiting
- Queen's Medical CenterRecruiting
- Straub Clinic and HospitalRecruiting
- Queen's Cancer Center - KuakiniRecruiting
- Northwestern UniversityRecruiting
- University of Chicago Comprehensive Cancer CenterRecruiting
- Northwestern Medicine Cancer Center KishwaukeeRecruiting
- NorthShore University HealthSystem-Evanston HospitalRecruiting
- Northwestern Medicine Cancer Center DelnorRecruiting
- NorthShore University HealthSystem-Glenbrook HospitalRecruiting
- NorthShore University HealthSystem-Highland Park Hospital
- Northwestern Medicine Lake Forest HospitalRecruiting
- UC Comprehensive Cancer Center at Silver CrossRecruiting
- University of Chicago Medicine-Orland ParkRecruiting
- Carle Cancer CenterRecruiting
- Northwestern Medicine Cancer Center WarrenvilleRecruiting
- McFarland Clinic - AmesRecruiting
- Iowa Methodist Medical Center
- Medical Oncology and Hematology Associates-Des MoinesRecruiting
- LSU Health Sciences Center at ShreveportRecruiting
- Tufts Medical CenterRecruiting
- Saint Joseph Mercy HospitalRecruiting
- Saint Joseph Mercy BrightonRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - BrightonRecruiting
- Saint Joseph Mercy CantonRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - CantonRecruiting
- Saint Joseph Mercy ChelseaRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - Chelsea HospitalRecruiting
- Hope Cancer Clinic
- Trinity Health Saint Mary Mercy Livonia HospitalRecruiting
- Huron Gastroenterology PCRecruiting
- Trinity Health IHA Medical Group Hematology Oncology Ann Arbor CampusRecruiting
- Essentia Health - Deer River ClinicRecruiting
- Essentia Health Cancer CenterRecruiting
- Essentia Health Hibbing ClinicRecruiting
- Essentia Health SandstoneRecruiting
- Essentia Health Virginia ClinicRecruiting
- Baptist Memorial Hospital and Cancer Center-OxfordRecruiting
- Baptist Memorial Hospital and Cancer Center-DesotoRecruiting
- Saint Luke's HospitalRecruiting
- Siteman Cancer Center at West County HospitalRecruiting
- Washington University School of MedicineRecruiting
- Siteman Cancer Center-South CountyRecruiting
- Siteman Cancer Center at Christian HospitalRecruiting
- Siteman Cancer Center at Saint Peters HospitalRecruiting
- Cancer Partners of Nebraska - Pine LakeRecruiting
- Southeast Nebraska Cancer Center - 68th Street PlaceRecruiting
- Memorial Sloan Kettering Basking RidgeRecruiting
- Englewood Hospital and Medical Center
- Monmouth Medical Center Southern Campus
- Monmouth Medical Center
- Memorial Sloan Kettering MonmouthRecruiting
- Memorial Sloan Kettering BergenRecruiting
- Rutgers Cancer Institute of New JerseyRecruiting
- Newark Beth Israel Medical Center
- Community Medical Center
- Roswell Park Cancer InstituteRecruiting
- Memorial Sloan Kettering CommackRecruiting
- Glens Falls Hospital
- Memorial Sloan Kettering WestchesterRecruiting
- NYU Winthrop HospitalRecruiting
- Laura and Isaac Perlmutter Cancer Center at NYU LangoneRecruiting
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer CenterRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- NYP/Weill Cornell Medical CenterRecruiting
- Upstate Cancer Center at OswegoRecruiting
- State University of New York Upstate Medical UniversityRecruiting
- Memorial Sloan Kettering NassauRecruiting
- Upstate Cancer Center Hematology Oncology at VeronaRecruiting
- UNC Lineberger Comprehensive Cancer CenterRecruiting
- Cleveland Clinic Cancer Center/Fairview HospitalRecruiting
- Cleveland Clinic FoundationRecruiting
- Ohio State University Comprehensive Cancer CenterRecruiting
- Cleveland Clinic Cancer Center IndependenceRecruiting
- Cleveland Clinic Cancer Center MansfieldRecruiting
- Hillcrest Hospital Cancer CenterRecruiting
- North Coast Cancer CareRecruiting
- Cleveland Clinic Cancer Center StrongsvilleRecruiting
- South Pointe HospitalRecruiting
- Cleveland Clinic Wooster Family Health and Surgery CenterRecruiting
- Cancer Centers of Southwest Oklahoma ResearchRecruiting
- University of Oklahoma Health Sciences CenterRecruiting
- Providence Saint Vincent Medical CenterRecruiting
- Portland VA Medical CenterRecruiting
- Medical University of South CarolinaRecruiting
- Saint Francis Cancer CenterRecruiting
- Baptist Memorial Hospital and Cancer Center-MemphisRecruiting
- Huntsman Cancer Institute/University of UtahRecruiting
- University of Virginia Cancer CenterRecruiting
- Inova Schar Cancer InstituteRecruiting
- FHCC OverlakeRecruiting
- Seattle Cancer Care Alliance at EvergreenHealth
- FHCC at Northwest HospitalRecruiting
- West Virginia University Charleston DivisionRecruiting
- Duluth Clinic AshlandRecruiting
- Marshfield Medical Center-EC Cancer CenterRecruiting
- Gundersen Lutheran Medical CenterRecruiting
- Marshfield Medical Center-MarshfieldRecruiting
- Marshfield Clinic-Minocqua CenterRecruiting
- Marshfield Medical Center-Rice LakeRecruiting
- Marshfield Medical Center-River Region at Stevens PointRecruiting
- Marshfield Medical Center - WestonRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Arm I (oral azacitidine, R-miniCHOP)
Arm II (R-miniCHOP)
Patients receive CC-486 PO for 7 days prior to cycle 1. Patients then receive CC-486 PO on days 8-21. Treatment repeats every 21 days for cycles 1-5 in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab IV (or SC for cycles 2-6), cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 21 days for cycles 1-6 (6 cycles total) in the absence of disease progression or unacceptable toxicity.
Patients receive rituximab IV (or SC for cycles 2-6), cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.