AzTrials
AzTrials

Ann Arbor Stage III Diffuse Large B-Cell LymphomaPhase 2/3NCT04799275

Testing CC-486 (Oral Azacitidine) Plus the Standard Drug Therapy in Patients 75 Years or Older With Newly Diagnosed Diffuse Large B Cell Lymphoma

A Phase 2/3 study testing Biospecimen Collection, Computed Tomography and Cyclophosphamide in people with Ann Arbor Stage III Diffuse Large B-Cell Lymphoma and Ann Arbor Stage IIX (Bulky) Diffuse Large B-Cell Lymphoma, run by National Cancer Institute (NCI) at 176 sites in United States.

Active, not recruiting

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

Official record

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Trial summary

This phase II/III trial compares the side effects and activity of oral azacitidine in combination with the standard drug therapy (reduced dose rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone [R-miniCHOP]) versus R-miniCHOP alone in treating patients 75 years or older with newly diagnosed diffuse… Read more about this study

Who is it for?
Ages 75 years and older
What is being tested?
Biospecimen Collection, Computed Tomography and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
422 participants
Where
176 sitesUnited States
Study dates
20 May 2021to 1 Mar 2027
Phase
Phase 2/3

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 75 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • 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)
Show all 45Show fewer
  • 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. PET-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. Participants must have measurable disease (at least one lesion with longest diameter ≥ 1.5 cm). 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 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 a history of acute leukemia having been treated with intensive induction therapy. Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • 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 be age ≥ 75
  • 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
  • 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)
  • 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
  • Participants must not have a concurrent primary malignancy undergoing active therapy. Exceptions: participants may have non-melanomatous skin cancers requiring only surgical intervention. Participants may have a history of early stage breast cancer or prostate cancer in remission after surgical and/or radiation therapy on adjuvant hormonal therapy only

Who cannot join

None listed.

Trial locations and contacts

176 sites in 1 country.

176 sites in 1 country

United States176 sites

  • Hawaii Cancer Care - Westridge

    ‘Aiea, Hawaii, 96701

  • Pali Momi Medical Center

    ‘Aiea, Hawaii, 96701

  • McFarland Clinic - Ames

    Ames, Iowa, 50010

  • Kaiser Permanente-Anaheim

    Anaheim, California, 92806

  • UI Health Care Mission Cancer and Blood - Ankeny Clinic

    Ankeny, Iowa, 50023

  • Trinity Health Saint Joseph Mercy Hospital Ann Arbor

    Ann Arbor, Michigan, 48106

  • Duluth Clinic Ashland

    Ashland, Wisconsin, 54806

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Emory Saint Joseph's Hospital

    Atlanta, Georgia, 30342

  • Augusta University Medical Center

    Augusta, Georgia, 30912

  • Kaiser Permanente-Baldwin Park

    Baldwin Park, California, 91706

  • Memorial Sloan Kettering Basking Ridge

    Basking Ridge, New Jersey, 07920

  • FHCC Overlake

    Bellevue, Washington, 98004

  • Kaiser Permanente-Bellflower

    Bellflower, California, 90706

  • Tower Cancer Research Foundation

    Beverly Hills, California, 90211

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Trinity Health IHA Medical Group Hematology Oncology - Brighton

    Brighton, Michigan, 48114

  • Trinity Health Medical Center - Brighton

    Brighton, Michigan, 48114

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Trinity Health IHA Medical Group Hematology Oncology - Canton

    Canton, Michigan, 48188

  • Trinity Health Medical Center - Canton

    Canton, Michigan, 48188

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • Centralia Oncology Clinic

    Centralia, Illinois, 62801

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Vandalia Health/CAMC Institute for Academic Medicine

    Charleston, West Virginia, 25304

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Chelsea Hospital

    Chelsea, Michigan, 48118

  • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

    Chelsea, Michigan, 48118

  • Saint Luke's Hospital

    Chesterfield, Missouri, 63017

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Illinois

    Chicago, Illinois, 60612

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • Cleveland Clinic Cancer Center/Fairview Hospital

    Cleveland, Ohio, 44111

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • UI Health Care Mission Cancer and Blood - West Des Moines Clinic

    Clive, Iowa, 50325

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Memorial Sloan Kettering Commack

    Commack, New York, 11725

  • UC Irvine Health Cancer Center-Newport

    Costa Mesa, California, 92627

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • Carle at The Riverfront

    Danville, Illinois, 61832

  • Dayton Physician LLC - Englewood

    Dayton, Ohio, 45415

  • Cancer Care Specialists of Illinois - Decatur

    Decatur, Illinois, 62526

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Essentia Health - Deer River Clinic

    Deer River, Minnesota, 56636

  • Northwestern Medicine Cancer Center Kishwaukee

    DeKalb, Illinois, 60115

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • UI Health Care Mission Cancer and Blood - Des Moines Clinic

    Des Moines, Iowa, 50309

  • UI Health Care Mission Cancer and Blood - Laurel Clinic

    Des Moines, Iowa, 50314

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Essentia Health Cancer Center

    Duluth, Minnesota, 55805

  • Marshfield Medical Center-EC Cancer Center

    Eau Claire, Wisconsin, 54701

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • Crossroads Cancer Center

    Effingham, Illinois, 62401

  • Englewood Hospital and Medical Center

    Englewood, New Jersey, 07631

  • NorthShore University HealthSystem-Evanston Hospital

    Evanston, Illinois, 60201

  • Inova Schar Cancer Institute

    Fairfax, Virginia, 22031

  • Kaiser Permanente-Fontana

    Fontana, California, 92335

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois, 60134

  • Glens Falls Hospital

    Glens Falls, New York, 12801

  • NorthShore University HealthSystem-Glenbrook Hospital

    Glenview, Illinois, 60026

  • Northwestern Medicine Glenview Outpatient Center

    Glenview, Illinois, 60026

  • Lutheran Hospital - Cancer Centers of Colorado

    Golden, Colorado, 80401

  • Northwestern Medicine Grayslake Outpatient Center

    Grayslake, Illinois, 60030

  • Saint Vincent Hospital Cancer Center Green Bay

    Green Bay, Wisconsin, 54301

  • Saint Vincent Hospital Cancer Center at Saint Mary's

    Green Bay, Wisconsin, 54303

  • Saint Francis Hospital

    Greenville, South Carolina, 29601

  • Saint Francis Cancer Center

    Greenville, South Carolina, 29607

  • Kaiser Permanente South Bay

    Harbor City, California, 90710

  • Memorial Sloan Kettering Westchester

    Harrison, New York, 10604

  • Essentia Health Hibbing Clinic

    Hibbing, Minnesota, 55746

  • NorthShore University HealthSystem-Highland Park Hospital

    Highland Park, Illinois, 60035

  • Hawaii Cancer Care Inc - Waterfront Plaza

    Honolulu, Hawaii, 96813

  • Queen's Cancer Cenrer - POB I

    Honolulu, Hawaii, 96813

  • Queen's Medical Center

    Honolulu, Hawaii, 96813

  • Straub Clinic and Hospital

    Honolulu, Hawaii, 96813

  • Queen's Cancer Center - Kuakini

    Honolulu, Hawaii, 96817

  • City of Hope Seacliff

    Huntington Beach, California, 92648

  • Cleveland Clinic Cancer Center Independence

    Independence, Ohio, 44131

  • City of Hope at Irvine Lennar

    Irvine, California, 92618

  • Kaiser Permanente-Irvine

    Irvine, California, 92618

  • Greater Dayton Cancer Center

    Kettering, Ohio, 45409

  • FHCC at EvergreenHealth

    Kirkland, Washington, 98034

  • Gundersen Lutheran Medical Center

    La Crosse, Wisconsin, 54601

  • Northwestern Medicine Lake Forest Hospital

    Lake Forest, Illinois, 60045

  • Monmouth Medical Center Southern Campus

    Lakewood, New Jersey, 08701

  • City of Hope Antelope Valley

    Lancaster, California, 93534

  • Cancer Centers of Southwest Oklahoma Research

    Lawton, Oklahoma, 73505

  • Cancer Partners of Nebraska

    Lincoln, Nebraska, 68516

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Hope Cancer Clinic

    Livonia, Michigan, 48154

  • Trinity Health Saint Mary Mercy Livonia Hospital

    Livonia, Michigan, 48154

  • City of Hope at Long Beach Elm

    Long Beach, California, 90813

  • Tibor Rubin VA Medical Center

    Long Beach, California, 90822

  • Monmouth Medical Center

    Long Branch, New Jersey, 07740

  • Kaiser Permanente Los Angeles Medical Center

    Los Angeles, California, 90027

  • Kaiser Permanente West Los Angeles

    Los Angeles, California, 90034

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • Cleveland Clinic Cancer Center Mansfield

    Mansfield, Ohio, 44906

  • Marshfield Medical Center-Marshfield

    Marshfield, Wisconsin, 54449

  • Carle Physician Group-Mattoon/Charleston

    Mattoon, Illinois, 61938

  • Hillcrest Hospital Cancer Center

    Mayfield Heights, Ohio, 44124

  • Baptist Memorial Hospital and Cancer Center-Memphis

    Memphis, Tennessee, 38120

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Memorial Sloan Kettering Monmouth

    Middletown, New Jersey, 07748

  • NYU Langone Hospital - Long Island

    Mineola, New York, 11501

  • Marshfield Medical Center - Minocqua

    Minocqua, Wisconsin, 54548

  • Ochsner LSU Health Monroe Medical Center

    Monroe, Louisiana, 71202

  • Memorial Sloan Kettering Bergen

    Montvale, New Jersey, 07645

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • UC Comprehensive Cancer Center at Silver Cross

    New Lenox, Illinois, 60451

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • NYP/Weill Cornell Medical Center

    New York, New York, 10065

  • Delaware Clinical and Laboratory Physicians PA

    Newark, Delaware, 19713

  • Helen F Graham Cancer Center

    Newark, Delaware, 19713

  • Medical Oncology Hematology Consultants PA

    Newark, Delaware, 19713

  • Newark Beth Israel Medical Center

    Newark, New Jersey, 07112

  • City of Hope Newport Beach

    Newport Beach, California, 92660

  • Cancer Care Center of O'Fallon

    O'Fallon, Illinois, 62269

  • Saint Vincent Hospital Cancer Center at Oconto Falls

    Oconto Falls, Wisconsin, 54154

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Kaiser Permanente-Ontario

    Ontario, California, 91761

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • Northwestern Medicine Orland Park

    Orland Park, Illinois, 60462

  • University of Chicago Medicine-Orland Park

    Orland Park, Illinois, 60462

  • Upstate Cancer Center at Oswego

    Oswego, New York, 13126

  • Baptist Memorial Hospital and Cancer Center-Oxford

    Oxford, Mississippi, 38655

  • Stanford Cancer Institute Palo Alto

    Palo Alto, California, 94304

  • Kaiser Permanente - Panorama City

    Panorama City, California, 91402

  • Illinois CancerCare-Peoria

    Peoria, Illinois, 61615

  • Providence Saint Vincent Medical Center

    Portland, Oregon, 97225

  • Portland VA Medical Center

    Portland, Oregon, 97239

  • Marshfield Medical Center-Rice Lake

    Rice Lake, Wisconsin, 54868

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • Kaiser Permanente-Riverside

    Riverside, California, 92505

  • Heartland Regional Medical Center

    Saint Joseph, Missouri, 64506

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • George E Wahlen Department of Veterans Affairs Medical Center

    Salt Lake City, Utah, 84148

  • Kaiser Permanente-San Diego Zion

    San Diego, California, 92120

  • Kaiser Permanente-San Marcos

    San Marcos, California, 92078

  • UCSF Cancer Center - San Mateo

    San Mateo, California, 94402

  • Essentia Health Sandstone

    Sandstone, Minnesota, 55072

  • North Coast Cancer Care

    Sandusky, Ohio, 44870

  • FHCC at Northwest Hospital

    Seattle, Washington, 98133

  • Saint Vincent Hospital Cancer Center at Sheboygan

    Sheboygan, Wisconsin, 53081

  • Memorial Hospital East

    Shiloh, Illinois, 62269

  • LSU Health Sciences Center at Shreveport

    Shreveport, Louisiana, 71103

  • City of Hope South Pasadena

    South Pasadena, California, 91030

  • Baptist Memorial Hospital and Cancer Center-Desoto

    Southhaven, Mississippi, 38671

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

  • Siteman Cancer Center at Christian Hospital

    St Louis, Missouri, 63136

  • Marshfield Medical Center-River Region at Stevens Point

    Stevens Point, Wisconsin, 54482

  • Cleveland Clinic Cancer Center Strongsville

    Strongsville, Ohio, 44136

  • Saint Vincent Hospital Cancer Center at Sturgeon Bay

    Sturgeon Bay, Wisconsin, 54235-1495

  • State University of New York Upstate Medical University

    Syracuse, New York, 13210

  • Community Medical Center

    Toms River, New Jersey, 08755

  • City of Hope South Bay

    Torrance, California, 90503

  • Banner University Medical Center - Tucson

    Tucson, Arizona, 85719

  • University of Arizona Cancer Center-North Campus

    Tucson, Arizona, 85719

  • Memorial Sloan Kettering Nassau

    Uniondale, New York, 11553

  • City of Hope Upland

    Upland, California, 91786

  • Carle Cancer Center

    Urbana, Illinois, 61801

  • Upstate Cancer Center at Verona

    Verona, New York, 13478

  • Essentia Health Virginia Clinic

    Virginia, Minnesota, 55792

  • South Pointe Hospital

    Warrensville Heights, Ohio, 44122

  • Northwestern Medicine Cancer Center Warrenville

    Warrenville, Illinois, 60555

  • Marshfield Medical Center - Weston

    Weston, Wisconsin, 54476

  • Kaiser Permanente-Woodland Hills

    Woodland Hills, California, 91367

  • Cleveland Clinic Wooster Family Health and Surgery Center

    Wooster, Ohio, 44691

  • Huron Gastroenterology PC

    Ypsilanti, Michigan, 48106

  • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

    Ypsilanti, Michigan, 48197

Other trials in United States

About this study

Official title: A Phase II/III Randomized Study of R-MiniCHOP With or Without CC-486 (Oral Azacitidine) in Participants Age 75 Years or Older With Newly Diagnosed Diffuse Large B Cell Lymphoma, Grade IIIB Follicular Lymphoma, Transformed Lymphoma, and High-Grade B-Cell Lymphomas With MYC AND BCL2 and/or BCL6 Rearrangements

This phase II/III trial compares the side effects and activity of oral azacitidine in combination with the standard drug therapy (reduced dose rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone [R-miniCHOP]) versus R-miniCHOP alone in treating patients 75 years or older with newly diagnosed diffuse large B cell lymphoma. R-miniCHOP includes a monoclonal antibody (a type of protein), called rituximab, which attaches to the lymphoma cells and may help the immune system kill these cells. R-miniCHOP also includes prednisone which is an anti-inflammatory medication and a combination of 3 chemotherapy drugs, cyclophosphamide, doxorubicin, and vincristine. These 3 chemotherapy drugs, as well as oral azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Combining oral azacitidine with R-miniCHOP may shrink the cancer or extend the time without disease symptoms coming back or extend patient's survival when compared to R-miniCHOP alone.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine if the addition of CC-486 (oral azacitidine) to R-miniCHOP results in excess toxicity compared to R-miniCHOP alone that would preclude the combination from being studied further. (Safety run-in) II. To determine if the CC-486 + R-miniCHOP regimen should be tested further (Phase III) against the control R-miniCHOP alone based on progression-free survival (PFS). (Phase II component) III. To compare the overall survival (OS) between CC-486 + R-miniCHOP and R-miniCHOP alone. (Phase III component)

SECONDARY OBJECTIVES:

  1. To assess the feasibility of delivering at least 4 cycles of CC-486 with R-miniCHOP in this population.

II. To assess toxicity for CC-486 + R-miniCHOP and for R-miniCHOP. III. To compare complete response rates, as defined by Lugano 2014 classification, between CC-486 + R-miniCHOP and R-miniCHOP alone.

INTEGRATED CORRELATIVE GERIATRIC ASSESSMENTS:

  1. To compare functioning as assessed by the S1918 Comprehensive Geriatric Assessment (S1918 CGA) between participants treated with CC-486 + R-miniCHOP versus R-miniCHOP alone.

II. To evaluate if frailty status (fit/unfit versus [vs] frail/superfrail) as assessed by the FIL tool is associated with OS.

III. To evaluate if frailty as measured by the FIL tool correlates with the summary frailty index as measured using components of the S1918 CGA.

BANKING OBJECTIVE:

  1. To bank specimens for future correlative studies.

OUTLINE:

Beginning 7 days prior to starting [protocol treatment, all patients receive vincristine sulfate intravenously (IV) on day 1, and prednisone orally (PO) daily on days 1-7.

Patients are then randomized to 1 of 2 arms.

ARM I: 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 rituximab and hyaluronidase human subcutaneously [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 undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) at screening and undergo positron emission tomography (PET)-computed tomography (CT) and blood sample collection throughout the study.

ARM II: Patients receive rituximab IV (or rituximab and hyaluronidase human 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. Patients undergo ECHO or MUGA at screening and undergo PET-CT and blood sample collection throughout the study.

After completion of study treatment, patients are followed up periodically until 5 years from the date of registration.

Being tested
Biospecimen Collection, Computed Tomography, Cyclophosphamide, Doxorubicin Hydrochloride, Echocardiography Test
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Lymphoma, B-Cell, Marginal Zone

What participants receive

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

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo PET-CT

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518

    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

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography

    Undergo ECHO

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan

    Undergo MUGA

  • Oral AzacitidineDrug

    Also called Azacitidine Oral, CC 486, CC-486, CC486

    Given PO

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET-CT

  • PrednisoneDrug

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

    Given PO

  • Questionnaire AdministrationOther

    Ancillary studies

  • RituximabBiological

    Also called ABP 798, ABP-798, ABP798, BI 695500

    Given IV

  • Rituximab and Hyaluronidase HumanBiological

    Also called Rituxan Hycela, Rituximab Plus Hyaluronidase, Rituximab/Hyaluronidase, Rituximab/Hyaluronidase Human

    Given SC

  • Vincristine SulfateDrug

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

    Given IV

Study groups in NCT04799275
Study groupRoleWhat they receive
Arm I (oral azacitidine, R-miniCHOP)ExperimentalPatients 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 rituximab and hyaluronidase human 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 undergo ECHO or MUGA at screening and undergo PET-CT and blood sample collection throughout the study.
Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Drug: Oral Azacitidine; Procedure: Positron Emission Tomography; Drug: Prednisone; Other: Questionnaire Administration; Biological: Rituximab; Biological: Rituximab and Hyaluronidase Human; Drug: Vincristine Sulfate
Arm II (R-miniCHOP)Active comparatorPatients receive rituximab IV (or rituximab and hyaluronidase human 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. Patients undergo ECHO or MUGA at screening and undergo PET-CT and blood sample collection throughout the study.
Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Procedure: Positron Emission Tomography; Drug: Prednisone; Other: Questionnaire Administration; Biological: Rituximab; Biological: Rituximab and Hyaluronidase Human; Drug: Vincristine Sulfate

What is being measured

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

  1. Excess toxicity as a result of adding oral azacitidine (CC-486) to reduced dose rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-miniCHOP) (Safety run-in)

    Will determine if the addition of CC-486 to R-miniCHOP results in excess toxicity compared to R-miniCHOP alone that would preclude the combination from being studied further.

    Measured: Up to completion of cycle 6

  2. Progression-free survival (PFS) (Phase II)

    Will determine if the CC-486 + R-miniCHOP regimen should be tested further (Phase III) against the control R-miniCHOP alone based on PFS. After accruing 130 patients (65 per arm, 21 months of accrual and potentially pausing accrual for 6 months follow-up to reach a target 63 events across arms), a one-sided stratified .10 log-rank test will inform a go/no-go decision based on sufficient evidence of efficacy to continue to the Phase III portion of the study.

    Measured: From date of registration to date of first observation of progressive disease according to the 2014 Lugano classification, or death due to any cause, assessed up to 1 year

  3. Overall survival (Phase III)

    Will compare overall survival in the control arm of R-miniCHOP to the experimental arm of CC-486 (oral azacitidine) + R-miniCHOP. Will be evaluated using a 1-sided .025 level stratified logrank test.

    Measured: From date of registration to date of death due to any cause, assessed up to 2 years

Secondary outcomes (3)

  1. Metabolic complete response (CR)

    Will be defined using 2014 Lugano classification. Fisher's exact test will be used to compare CR rates between the experimental arm of CC-486 + R-miniCHOP and the control arm of R-miniCHOP alone.

    Measured: Up to end of cycle 6 or end of treatment

  2. Incidence of adverse events

    Will be assessed using Common Terminology Criteria for Adverse Events version 5. The maximum Grade for each toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. Treatment-related toxicities between arms will be compared using Fisher's exact test.

    Measured: Until disease progression, assessed up to 5 years

  3. Overall survival (Phase III)

    An additional secondary analysis of overall survival of the Phase III comparison will adjust for patients with identified double-hit phenotype in addition to the pre-specified stratification factors. Will also prospectively collect the number of days between diagnostic biopsy and cycle 1 day 1 of therapy for a pre-planned secondary analysis.

    Measured: From date of registration to date of death due to any cause, assessed up to 5 years

Timeline

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

  1. First posted16 Mar 2021
  2. Study start20 May 2021
  3. Primary completion1 Mar 2027 (estimated)
  4. Study completion1 Mar 2027 (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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
422 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04799275
Sponsor's protocol ID
NCI-2020-01256
Other IDs
NCI-2020-01256, S1918, S1918, U10CA180888
Status last verified
Apr 2026
First submitted
13 Mar 2021
Last updated
1 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Publications

  • Brem EA, Li H, Beaven AW, Caimi PF, Cerchietti L, Alizadeh AA, Olin R, Henry NL, Dillon H, Little RF, Laubach C, LeBlanc M, Friedberg JW, Smith SM. SWOG 1918: A phase II/III randomized study of R-miniCHOP with or without oral azacitidine (CC-486) in participants age 75 years or older with newly diagnosed aggressive non-Hodgkin lymphomas - Aiming to improve therapy, outcomes, and validate a prospective frailty tool. J Geriatr Oncol. 2022 Mar;13(2):258-264. doi: 10.1016/j.jgo.2021.10.003. Epub 2021 Oct 20.

    PubMed 34686472

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