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

Active:	Yes
Cancer Type:	Lymphoma	NCT ID:	NCT04799275
Trial Phases:	Phase II Phase III	Protocol IDs:	S1918 (primary) S1918 NCI-2020-01256
Eligibility:	75 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	SWOG
NCI Full Details:	http://clinicaltrials.gov/show/NCT04799275

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 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.

Objectives

PRIMARY OBJECTIVES:
I. 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:
I. 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:
I. 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:
I. 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 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 blood sample collection throughout the study.

ARM II: 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. Patients undergo blood sample collection throughout the study.

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

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