Efficacy and Safety of Oral Azacitidine Compared to Investigator's Choice Therapy in Patients With Relapsed or Refractory AITL

NCT03593018 | Completed Phase 3 DMC

• 1 other identifier: ORACLE
• Study Type: interventional
• Target: 86
• Locations: 5 countries
• Sites: 27

Brief Summary

This study evaluates the efficacy of Oral azacitidine versus single-agent Investigator's Choice Therapy in patients with Relapsed or Refractory Angioimmunoblastic T-cell Lymphoma.

Conditions

Relapsed Angioimmunoblastic T-Cell Lymphoma; Refractory Angioimmunoblastic T-cell Lymphoma

Keywords

oral azacitidine

Outcome Measures

Primary Outcomes (2)

• Progression Free Survival (PFS)

  PFS using local assessment of progressive disease according to Lugano Response Criteria (2014)

  18 months after first randomisation (when 18 events will occur)

• Progression Free Survival (PFS)

  PFS using local assessment of progressive disease according to Lugano Response Criteria (2014)

  35 months after first randomisation (when 61 events will occur)

Secondary Outcomes (9)

• Overall survival (OS)

  40 months after first randomisation (when 57 deaths will occur) or 2 years after last randomisation

• PFS by the Independent Review Committee (IRC)

  40 months after first randomisation (when 57 deaths will occur) or 2 years after last randomisation

• Overall response rate

  40 months after first randomisation (when 57 deaths will occur) or 2 years after last randomisation

• Complete response rate (CRR)

  40 months after first randomisation (when 57 deaths will occur) or 2 years after last randomisation

• Duration of response (DoR)

  40 months after first randomisation (when 57 deaths will occur) or 2 years after last randomisation

Study Arms (2)

Oral Azacitidine

EXPERIMENTAL

Oral azacitidine 300mg during 14 first days of 28-days cycle for European (EU) patients, Oral azacitidine 200mg during 14 first days of 28-days cycle for Asian patients (Treatment until progression, patient decision or toxicity)

Drug: Oral azacitidine

Investigator's choice therapy

ACTIVE COMPARATOR

Romidepsin 14mg/m² on days 1, 8 and 15 of a 28-days cycle (Treatment until progression, patient decision or toxicity) or Bendamustine 120mg/m² on days 1 and 2 of a 21-days cycle (during 6 cycles) or Gemcitabine 1200mg/m² on days 1, 8 and 15 of a 28-days cycle (during 6 cycles)

Drug: Romidepsin; Drug: Bendamustine; Drug: Gemcitabine

Interventions

Oral azacitidine DRUG

Azacitidine tablets

Also known as: CC-486

Oral Azacitidine

Romidepsin DRUG

Romidepsin injection

Also known as: Istodax

Investigator's choice therapy

Bendamustine DRUG

Bendamustine injection

Also known as: Levact

Investigator's choice therapy

Gemcitabine DRUG

Gemcitabine injection

Also known as: Gemzar

Investigator's choice therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must satisfy all following criteria to be enrolled in the study::
• Patient is ≥ 18 years of age at the time of signing the informed consent form (ICF).
• Patient must understand and voluntarily sign an ICF prior to any study-specific assessments/procedures being conducted.
• Patient is willing and able to adhere to the study visit schedule and other protocol requirements
• Patient had local diagnosed peripheral T cell lymphoma (PTCL) with T-follicular helper (TFH) phenotype according to the criteria of the latest World Health Organization (WHO) classification based on a surgical lymph node biopsy including any one of
• Angioimmunoblastic T cell lymphoma (AITL)
• Follicular T cell lymphoma
• Nodal peripheral T-cell lymphoma with TFH phenotype There should be a documented expression of minimum two TFH markers among this panel of markers : CD10, CXCL13, PD1, ICOS and BCL6 by the tumoral cells by immunohistochemistry. Biopsy at relapse or progression is not mandatory, but highly encouraged on a surgical or needle core biopsy, and diagnostic tissue should be available for central pathology review and for ancillary molecular studies.
• Local pathology report should be reviewed by the sponsor's medical monitor prior to enrollment.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 3
• Meet the following lab criteria:
• Absolute Neutrophil Count (ANC) ≥ 1,5 x 109/L (≥ 1 x 109/L if bone marrow (BM) involvement by lymphoma)
• Platelet ≥ 75 x 109/L (≥ 50 x 109/L if BM involvement by lymphoma)
• Hemoglobin ≥ 8 g/dL.
• Anticipated life expectancy at least 3 months

You may not qualify if:

• Presence of any of the following will exclude a patient from enrollment:
• Clinical evidence of central nervous system involvement by lymphoma. Patients with suspicion of central nervous system (CNS) involvement must undergo neurologic evaluation and CT/MRI of head and lumbar puncture to exclude CNS disease.
• Any significant medical conditions, laboratory abnormality or psychiatric illness likely to interfere with participation in this clinical study (according to the investigator's decision)
• Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment)
• Known Human Immunodeficiency Virus (HIV) or Hepatitis C Virus (HCV) infection, or evidence of positive HTLV1 serology or of active Hepatitis B (HB) Virus (HBV) infection defined as:
• HB s Ag positive
• HB s Ag negative, anti-HB s antibody positive and/or anti-HB c antibody positive with detectable viral DNA
• Impaired renal function (MDRD formula or Cockcroft-Gault Creatinine Clearance \< 30 ml/min) or impaired liver function tests (Serum total bilirubin level \> 2.0 mg/dl \[34 µmol/L\] (except in case of Gilbert's Syndrome, or documented liver or pancreatic involvement by lymphoma), Serum transaminases (AST or ALT) \> 3 upper normal limits) unless they are related to the lymphoma.
• Active malignancy other than the one treated in this research. Prior history of malignancies, other than low risk MDS or chronic myelomonocytic leukemia (CMML) (with less than 5% blasts in bone marrow), unless the patient has been free of the disease for ≥ 3 years. However, patients with the following history/concurrent conditions are allowed:
• Basal or squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix
• Carcinoma in situ of the breast
• Incidental histologic finding of prostate cancer (T1a or T1b) using the tumor-nodes-metastasis (TNM)\] clinical staging system
• Early-stage gastric cancer suitable for endoscopic mucosal resection or endoscopic submucosal dissection
• Treatment with any investigational drug within 5 half-lives before planned first cycle of study treatment and during the study. Ongoing medically significant adverse events from previous treatment, regardless of the time period.

Sponsors & Collaborators

• The Lymphoma Academic Research Organisation: lead
• Celgene: collaborator

Study Sites (27)

University Hospital for Internal Medicine - University Hospital Graz

Graz, Austria

Location

Medical University of Vienna

Vienna, Austria

Location

A. Z. Sint-Jan Brugge-Oostende AV

Bruges, Belgium

Location

Cliniques Universitaires de Bruxelles - Hôpital Erasme

Brussels, Belgium

Location

CHU UCL Namur - Site Godinne

Yvoir, Belgium

Location

Aarhus University Hospital

Aarhus, Denmark

Location

Institut d'Hématologie de Basse Normandie

Caen, France

Location

CHU de Clermont-Ferrand - Hôpital Estaing

Clermont-Ferrand, France

Location

CHU Henri Mondor

Créteil, France

Location

CHU de Dijon

Dijon, France

Location

CHU de Grenoble

Grenoble, France

Location

CHRU de Lille

Lille, France

Location

CHU de Montpellier - Hôpital Saint-Eloi

Montpellier, France

Location

CHU de Nantes - Hôtel Dieu

Nantes, France

Location

Hôpital Necker

Paris, France

Location

Hôpital Saint-Louis

Paris, France

Location

CHU Haut-Lévèque - Centre François Magendie

Pessac, France

Location

CHU Lyon-Sud

Pierre-Bénite, France

Location

CH Annecy Genevois

Pringy, France

Location

CHU Pontchaillou

Rennes, France

Location

Centre Henri Becquerel

Rouen, France

Location

IUCT - Oncopole

Toulouse, France

Location

CHRU de Nancy - Hôpital de Brabois

Vandœuvre-lès-Nancy, France

Location

University College London Hospital

London, United Kingdom

Location

The Christie

Manchester, United Kingdom

Location

Nottingham City Hospital

Nottingham, United Kingdom

Location

Churchill Hospital

Oxford, United Kingdom

Location

Related Publications (1)

• Dupuis J, Bachy E, Morschhauser F, Cartron G, Fukuhara N, Daguindau N, Casasnovas RO, Snauwaert S, Gressin R, Fox CP, d'Amore FA, Staber PB, Tournilhac O, Bouabdallah K, Thieblemont C, Andre M, Rai S, Ennishi D, Gkasiamis A, Nishio M, Fornecker LM, Delfau-Larue MH, Sako N, Mule S, de Leval L, Gaulard P, Tsukasaki K, Lemonnier F. 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. Lancet Haematol. 2024 Jun;11(6):e406-e414. doi: 10.1016/S2352-3026(24)00102-9.

  PMID: 38796193 DERIVED

Related Links

• Website of The Lymphoma Study Research Organisation (LYSARC)

MeSH Terms

Conditions

Immunoblastic Lymphadenopathy

Interventions

Azacitidine; cc-486; romidepsin; Bendamustine Hydrochloride; Gemcitabine

Condition Hierarchy (Ancestors)

Lymphadenopathy; Lymphatic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Butyrates; Acids, Acyclic; Carboxylic Acids; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxycytidine

Study Officials

• Jehan DUPUIS, MD

  Henri Mondor University Hospital

  STUDY CHAIR

• François LEMONNIER, MD

  Henri Mondor University Hospital

  STUDY CHAIR

• Kunihiro TSUKASAKI, MD

  Saitama Medical University International Medical Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2018
• First Posted: July 19, 2018
• Study Start: November 9, 2018
• Primary Completion: February 10, 2021
• Study Completion: August 28, 2025
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (17); BE (3); AU (2); DK (1); GB (4)