Onureg (azacitidine oral) / BMS - LARVOL DELTA

Oral azacitidine compared with standard therapy in patients with relapsed or refractory follicular helper T-cell lymphoma (ORACLE): an open-label randomised, phase 3 study. (PubMed, Lancet Haematol) - P3 | "Although the pre-specified primary outcome of the trial was not met, the favourable safety profile suggests that azacitidine could add to the treatment options in these difficult to treat diseases especially in combination with other drugs. Trials with combination are in preparation in a platform trial."

Clinical • IO biomarker • Journal • P3 data • P3 data • Candidiasis • Cardiovascular • Congestive Heart Failure • Follicular Lymphoma • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • T Cell Non-Hodgkin Lymphoma • BCL6 • CXCL13 • ICOS • MME • PD-1

CLINICAL AND BIOLOGICAL MARKERS ASSOCIATED WITH LONG-TERM SURVIVAL FOR PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML) IN REMISSION AFTER CHEMOTHERAPY IN THE QUAZAR AML-001 TRIAL OF ORAL AZACITIDINE (EHA 2022) - "Conclusion Oral-AZA Tx was significantly associated with LTS vs PBO. In univariate analysis, Int-risk cytogenetics and NPM1 mut at Dx, and MRD response on-study, were significantly prognostic of LTS in both arms, whereas MRD– status at BL (post-IC) was associated with LTS only in the PBO arm."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD4 • CD8 • FLT3 • HAVCR2 • NPM1 • PD-1

A Phase 1 Trial of Duvelisib and Oral Azacitidine in Relapsed/Refractory T-Cell Lymphoma. (PubMed, Hematol Oncol) - P1 | "Randomized evaluation focused on the TFH subtype is warranted. TRIAL REGISTRATION: NCT05065866."

Journal • P1 data • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia • Transplantation • PIK3CG

Results from a Phase 1 Open-Label Dose Escalation and Expansion Trial of Oral Azacitidine + Cedazuridine (ASTX030) in Patients with Myelodysplastic Syndromes (MDS) and MDS/Myeloproliferative Neoplasms (MPN) (ASH 2024) - P2/3 | "Background : Azacitidine (AZA) and decitabine (DEC) are parenteral DNA methyltransferase inhibitors (DNMTis) approved for the treatment of patients with MDS and acute myeloid leukemia...Median age was 72 years (range, 26–87), 35% (n=31) of patients were female, prior treatments included DNMTis (9% [n=8]), luspatercept (3% [n=3]), lenalidomide (3% [n=3]), and erythropoiesis‑stimulating agents (3% [n=2])...Based on the results of the phase 1 trial, 140/20 mg AZA/CED was selected as the RP2D. Enrollment for the phase 2 randomized, crossover (oral vs SC) trial is ongoing and combination dosing is in preparation."

Clinical • P1 data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Leukopenia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Neutropenia • Oncology • Thrombocytopenia

Multicenter Phase 2 Study of Oral azacitidine (CC-486) plus CHOP as initial treatment for peripheral T-cell lymphoma. (PubMed, Blood) - P2 | "DNA methylation did not show significant shift. This safe and active initial therapy regimen is being further evaluated in the ALLIANCE randomized study A051902 in CD30-negative PTCL."

Journal • P2 data • Fatigue • Febrile Neutropenia • Hematological Malignancies • Immunology • Lymphoma • Neutropenia • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • DNMT3A • IDH2 • RHOA • TET2 • TNFRSF8

Targeting the methylome in T-LGL leukemia: Pre-clinical analysis and Results of a Phase I trial with oral 5-azacytidine (ASH 2025) - P1/2 | "In vivo, NSG huIL-15 mice engrafted with LGLLcells and treated with 5-aza (3 mg/kg) showed significant LGLL reduction via IVIS imaging and improvedoverall survival (n=5 each, p<0.001), supporting the potential of epigenetic therapy in LGLL therapy.Given the strong preclinical impact of 5-aza on T-LGLL cells, we initiated a multi-center Phase I/II trialusing oral 5-aza (CC-486) in relapsed/refractory T-LGLL patients (NCT05141682)...In vitro, in vivo, and Phase I trial datashow that epigenomic targeting with 5-aza yields clinical responses across doses without DLTs. The PhaseII component of the oral 5-aza clinical trial is currently ongoing, reinforcing the critical role of themethylome in T-LGLL pathogenesis."

P1 data • Preclinical • Gene Therapies • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • T-Cell Large Granular Lymphocyte Leukemia • CD5 • CD8 • IL15

Preliminary safety and efficacy of oral azacitidine (Oral-AZA) in patients (pts) with low-/Intermediate (Int)-risk myelodysplastic syndromes (MDS): Phase 2 results from the ASTREON trial. (ASCO 2024) - P2/3 | "Most pts (42/47 [89.4%]) had prior MDS tx, including but not limited to erythropoiesis-stimulating agents, lenalidomide, luspatercept, and imetelstat. The safety of Oral-AZA 200 mg and 300 mg was consistent with the known Oral-AZA safety profile. Preliminary efficacy data support continued evaluation of Oral-AZA in LR-MDS."

Clinical • P2 data • Acute Myelogenous Leukemia • Anemia • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

ORAL AZACITIDINE VS MIDOSTAURIN AS MAINTENANCE TREATMENT FOR FLT3 MUTANT ACUTE MYELOID LEUKEMIA IN COMPLETE REMISSION: AN INDIRECT TREATMENT COMPARISON (EHA 2022) - P3 | "Limitations included trial differences and small sample size. More research is needed to support this observation."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • FLT3

All-Oral Treatment in Patients Older Than 65 Years With Newly Diagnosed Acute Myelogenous Leukemia: Progression-Free Survival and Toxicity (SOHO 2026) - "They received continuous venetoclax 100 mg/day and oral azacitidine 300 mg/day for 14 days followed by 14 days rest; treatment continued until disease progression or major toxicity. Oral treatment seems to be an efficient treatment in older patients with newly diagnosed acute myelogenous leukemia, demonstrating good response and toxicity profile."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

A Phase II Study of Azacitidine Plus Venetoclax As Maintenance Therapy in Acute Myeloid Leukemia: Durable Responses with Longer Term Follow-up (ASH 2022) - P2 | "Oral azacitidine (CC-486) has been shown to improve relapse-free survival (RFS) and overall survival (OS) in patients with AML who have achieved first complete remission (CR) after intensive chemotherapy, and is currently the only agent approved as maintenance therapy in AML... This phase II study enrolled patients with AML ≥ 18 years, not immediately eligible for SCT, and who had achieved a first CR/CRi (regardless of measurable residual disease [MRD] status) following at least 2 cycles of intensive chemotherapy (defined as intermediate or higher dose cytarabine; cohort 1) or low-intensity therapy (defined as hypomethylating agent or low-dose cytarabine-based; cohort 2)... With over 13 months of follow up, this is the first experience demonstrating the tolerability and feasibility of low-dose AZA plus VEN as maintenance therapy in AML. RFS and OS are encouraging, especially in the non-adverse risk ELN categories (favorable or intermediate). Further studies are..."

Clinical • P2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Thrombocytopenia • Transplantation

Reduced dose azacitidine plus venetoclax as maintenance therapy in acute myeloid leukaemia following intensive or low-intensity induction: a single-centre, single-arm, phase 2 trial. (PubMed, Lancet Haematol) - P2 | "Low dose azacitidine plus venetoclax is a feasible maintenance strategy in acute myeloid leukaemia following intensive and low-intensity induction."

Journal • P2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Leukopenia • Neutropenia • Oncology • Respiratory Diseases • Thrombocytopenia • Transplantation

Oral azacitidine prolongs survival of patients with AML in remission independent of measurable residual disease status. (PubMed, Blood) - P3 | "While presence or absence of MRD was a strong prognostic indicator of OS and RFS, there were added survival benefits with Oral-AZA maintenance therapy compared with placebo, independent of patients' MRD status at baseline. NCT01757535 Clinicaltrials.gov."

Clinical • Journal • Residual disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

Comparative Efficacy and Safety of Oral Azacitidine (CC-486) Versus Injectable Hypomethylating Agents as Maintenance Therapy Following Allogeneic Haematopoietic Cell Transplantation in Myelodysplastic Neoplasms: A Systematic Review and Network Meta-Analysis (SOHO 2026) - P3 | " Twenty-five studies (n = 5847) were included—3 randomized controlled trials and 22 prospective or controlled retrospective cohorts-evaluating 5 treatment nodes: CC-486, injectable azacitidine, injectable decitabine, oral decitabine/cedazuridine, and observation. HMA maintenance post-alloHCT significantly improves survival and reduces relapse in MDS, with a favorable GVHD and NRM profile. CC-486 shows the most promising RFS estimate in indirect comparison, but superiority over injectable agents cannot be confirmed without head-to-head randomized evidence."

Retrospective data • Review • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Efficacy and Safety of Hypomethylating Agent Maintenance Therapy in Transplant-Ineligible Acute Myeloid Leukemia in First Remission: A Systematic Review and Meta-Analysis (SOHO 2026) - "In transplant-ineligible AML patients in CR1, receiving HMA maintenance was associated with favorable outcomes. Hematologic toxicity, as expected, was the principal adverse event signal of grade ≥3 consequence. Although CC-486 is approved for this indication, its adoption has not been widespread due to tolerability issues, especially gastrointestinal toxicities, and because it showed similar 1-year OS and worse 1-year DFS in the QUAZAR trial, showing a possible indication for parenteral HMA maintenance in its place."

Retrospective data • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

High Rates of Remission with the Initial Treatment of Oral Azacitidine Plus CHOP for Peripheral T-Cell Lymphoma (PTCL): Clinical Outcomes and Biomarker Analysis of a Multi-Center Phase II Study (ASH 2021) - P2 | "This study demonstrates that priming with oral azacitidine (CC486) in combination with CHOP as initial therapy is safe, effective, and produces sustained remission in PTCL-TFH subtype. Epigenetic priming with azacitidine appears to inhibit the proliferation of TFH lymphoma cells, providing potential synergistic mechanism of action with chemotherapy. This active combination will be further evaluated in the upcoming ALLIANCE/ US Intergroup randomized study A051902, comparing oral azacitidine-CHO(E)P vs duvelisib-CHO(E)P against CHO(E)P in CD30 negative PTCL."

Biomarker • Clinical • Clinical data • P2 data • Anemia • Anorexia • Bone Marrow Transplantation • Cardiovascular • Fatigue • Febrile Neutropenia • Heart Failure • Hematological Malignancies • Immunology • Inflammation • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia • Transplantation • DNMT3A • IDH2 • RHOA • TET2 • TNFRSF8 • TRB

Results from a Clinical Study of the All-Oral Regimen of CC-486 (Oral Azacitidine) and Venetoclax for Newly Diagnosed and Relapsed and Refractory Acute Myeloid Leukemia (ASH 2024) - "The MTD of CC-486 in combination with ven was previously reported as 300mg QD d1-14 in relapsed/refractory (R/R) AML (Amaya et al. High response rates have been seen in the newly diagnosed cohort with 7/7 (100%) of the patients achieving a CR/CRi, including 3/3 who harbor a TP53 mutation. Final results of the R/R cohort, as well as a larger sample size of the ND subjects, with genomic annotation, as well as translational studies exploring mechanistic differences and similarities with this all-oral regimen and conventional aza/ven, will be presented."

Clinical • Acute Myelogenous Leukemia • Anemia • Fatigue • Febrile Neutropenia • Neutropenia • Thrombocytopenia • TP53

Posttransplant Oral Azacitidine Maintenance: Clinical Outcomes and Immune Landscape (SOHO 2026) - P1 | "Oral AZA maintenance after allo-HSCT is feasible, well tolerated, and preserves key immune function. Ongoing prospective studies (Amadeus, NCT03613532) will help define optimal use, dosing, and patient selection. AML: acute myeloid leukemia, CMML: chronic myelomonocytic leukemia, CPSS: CMML-specific prognostic scoring system, CR1: first complete remission, ELN: European LeukemiaNet, HLA-DR: human leukocyte antigen-DR isoptype, IPSS–M: International Prognostic Scoring System–Molecular, MDS: myelodysplastic syndromes, MRD: measurable residual disease, OS: overall survival, RFS: relapse-free survival."

Clinical • Clinical data • Post-transplantation • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD8

A pilot trial evaluating lenalidomide and oral azacitidine with radiotherapy for patients with newly diagnosed and relapsed plasmacytoma. (PubMed, Haematologica) - "Not available."

Journal • Oncology • Plasmacytoma

CLONAL ARCHITECTURE OF RELAPSED OR REFRACTORY FOLLICULAR HELPER T-CELL LYMPHOMA: AN ANCILLARY STUDY OF THE ORACLE TRIAL, A LYSA STUDY (ICML 2023) - P3 | "To describe and characterize the clonal architecture of refractory/relapsed (R/R) TFHL, we collected bone marrow samples of patients included in the ORACLE trial (NCT03593018), a phase 3 trial evaluating the oral 5-azacitidine (CC-486) compared to single-agent chemotherapy in patients with R/R TFHL...In conclusion, CH is very frequent in TFHL, and more than half of them are TFHL-related. Encore Abstract—previously submitted to EHA 2023"

Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • DNMT3A • IDH2 • RHOA • TET2

Prognostic impact of NPM1 and FLT3 mutations in patients with AML in first remission treated with oral azacitidine. (PubMed, Blood) - P3 | "Median OS with Oral-AZA vs placebo was 28.2 vs 16.2 months, respectively, for FLT3mut/MRD- patients, and 24.0 vs 8.0 months for FLT3mut/MRD+ patients. In multivariate analyses, Oral-AZA significantly improved survival independent of NPM1 or FLT3 mutational status, cytogenetic risk, or post-IC MRD status."

Journal • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Transplantation • FLT3 • NPM1

A POST HOC ANALYSIS OF OUTCOMES OF PATIENTS WITH ACUTE MYELOID LEUKEMIA WITH MYELODYSPLASIA-RELATED CHANGES WHO RECEIVED ORAL AZACITIDINE MAINTENANCE THERAPY IN THE QUAZAR AML-001 STUDY (EHA 2024) - "Oral-AZA significantly improved OS and RFS compared with PBO for patients with AML-MRC indicating that Oral-AZA maintenance is an effective treatment option for these patients with particularly poor prognosis."

Clinical • Retrospective data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation

Oral Azacitidine Maintenance vs Observation in Acute Myeloid Leukemia in First Remission: A Systematic Review and Pooled Analysis of Randomized Evidence (SOHO 2026) - "Across randomized and near-randomized evidence, oral azacitidine–based maintenance strategies were associated with improved survival outcomes compared with observation in patients with AML in first remission. While the magnitude of benefit is driven largely by high-quality randomized data, the consistency across supportive cohorts reinforces the role of maintenance therapy in this setting. These findings support broader adoption of oral azacitidine while highlighting the need for further randomized data to refine patient selection and optimize treatment duration."

Retrospective data • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Oral Azacytidine in Patients with Relapsed/Refractory Angioimmunoblastic T-Cell Lymphoma: Final Analysis of the Oracle Phase III Study (ASH 2022) - P3 | "Patients & Eighty-six patients with relapsed/refractory AITL or nodal follicular helper T-cell lymphoma were randomized between CC-486 (n=42) and investigator's choice (gemcitabine, n=24, bendamustine n=16, romidepsin n=4) between November 2018 and February 2021. The trial did not meet its primary endpoint, most likely due to an optimistic hypothesis of PFS improvement, resulting in a study including 86 patients which could be underpowered to detect a clinically meaningful difference. 5-azacytidine had a favourable safety profile compared to standard of care and was associated with prolonged overall survival, suggesting that this drug might have a role in the treatment of TFH PTCL and could be investigated in combination with other agents."

Clinical • P3 data • Follicular Lymphoma • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia • DNMT3A • IDH2 • RHOA • TET2

A051902: Testing the Addition of Duvelisib or CC-486 to the Usual Treatment for Peripheral T-Cell Lymphoma (clinicaltrials.gov) - P2 | N=170 | Recruiting | Sponsor: Alliance for Clinical Trials in Oncology | Suspended ➔ Recruiting

Enrollment open • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • BCL6 • CXCL13 • ICOS • MME • PD-1 • TNFRSF8

Long-term survival with oral azacitidine for patients with acute myeloid leukemia in first remission after chemotherapy: updated results from the randomized, placebo-controlled, phase 3 QUAZAR AML-001 trial. (PubMed, Am J Hematol) - No abstract available

Journal • P3 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology