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

Running, not enrolling · Phase 2/Phase 3

Conditions studied: 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, Diffuse Large B-Cell Lymphoma Activated B-Cell Type, Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation, Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, Grade 3b Follicular Lymphoma, HHV8-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements, High Grade B-Cell Lymphoma, Not Otherwise Specified, Intravascular Large B-Cell Lymphoma, Lymphoplasmacytic Lymphoma, Nodular Lymphocyte Predominant B-Cell Lymphoma, Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type, T-Cell/Histiocyte-Rich Large B-Cell Lymphoma, Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma, Transformed Marginal Zone Lymphoma to Diffuse Large B-Cell Lymphoma

In brief

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.

Key facts

Study ID

NCT04799275

Run by

National Cancer Institute (NCI)

People needed

422

Starts

2021-05-20

Expected to finish

2027-03-01

Last updated by the study team

2026-07-08

Who can join

Age: 75 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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. 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

Where it is running

• University of Arizona Cancer Center-North Campus — Tucson, Arizona, United States
• University of Arkansas for Medical Sciences — Little Rock, Arkansas, United States
• Kaiser Permanente-Anaheim — Anaheim, California, United States
• Kaiser Permanente-Baldwin Park — Baldwin Park, California, United States
• Kaiser Permanente-Bellflower — Bellflower, California, United States
• Tower Cancer Research Foundation — Beverly Hills, California, United States
• UC Irvine Health Cancer Center-Newport — Costa Mesa, California, United States
• City of Hope Comprehensive Cancer Center — Duarte, California, United States
• Kaiser Permanente-Fontana — Fontana, California, United States
• Kaiser Permanente South Bay — Harbor City, California, United States
• City of Hope Seacliff — Huntington Beach, California, United States
• City of Hope at Irvine Lennar — Irvine, California, United States
• Kaiser Permanente-Irvine — Irvine, California, United States
• City of Hope Antelope Valley — Lancaster, California, United States
• City of Hope at Long Beach Elm — Long Beach, California, United States
• Tibor Rubin VA Medical Center — Long Beach, California, United States
• Kaiser Permanente Los Angeles Medical Center — Los Angeles, California, United States
• Kaiser Permanente West Los Angeles — Los Angeles, California, United States
• Cedars-Sinai Medical Center — Los Angeles, California, United States
• City of Hope Newport Beach — Newport Beach, California, United States
• Kaiser Permanente-Ontario — Ontario, California, United States
• UC Irvine Health/Chao Family Comprehensive Cancer Center — Orange, California, United States
• Stanford Cancer Institute Palo Alto — Palo Alto, California, United States
• Kaiser Permanente - Panorama City — Panorama City, California, United States
• Banner University Medical Center - Tucson — Tucson, Arizona, United States

Full record on ClinicalTrials.gov

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