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AzTrials

Relapsed Angioimmunoblastic T-Cell LymphomaPhase 3NCT03593018

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

A Phase 3 study testing Oral azacitidine, Romidepsin and Bendamustine in people with Relapsed Angioimmunoblastic T-Cell Lymphoma and Refractory Angioimmunoblastic T-cell Lymphoma, run by The Lymphoma Academic Research Organisation at 27 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Oral azacitidine, Romidepsin and Bendamustine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
86 participants
Where
27 sitesin 5 countries
Study dates
9 Nov 2018to 28 Aug 2025
Phase
Phase 3
Are there results?
None posted in the registry

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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
  • Relapsed (after partial or complete response) or refractory AITL after at least one line of systemic therapy (there is no mandatory resting period after the previous treatment as long as the biochemistry and hematology labs meet the inclusion criteria as below.)
  • 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
  • At least one measurable lesion on CT that is greater than 1.5 cm in the longest diameter for nodal lesions and greater than 1.0 cm in the longest diameter for extranodal lesions. The lesion must be measurable in two perpendicular dimensions. Patients with only cutaneous disease will be excluded.
  • Female patient of childbearing potential (FCBP) may participate, providing she meets the following conditions:
  • Have two negative pregnancy tests as verified by the investigator prior to starting study treatment: serum pregnancy test at Screening and negative serum or urine pregnancy test (investigator's discretion) within 72 hours prior to starting treatment with study treatment (Cycle 1 Day 1). She must agree to ongoing pregnancy testing during the study (before beginning each subsequent cycle of treatment), and 28 days after the last study drug administration. This applies even if the patient practices complete abstinence from heterosexual contact.
  • Agrees to practice true abstinence (which must be reviewed monthly and source documented) or agrees to the use of highly effective methods of contraception from 28 days prior to starting study treatment, and must agree to continue using such precautions during study treatment (including dose interruptions) and for up to 90 days after the last study drug administration. True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation, symptom-thermal, post ovulation methods) and withdrawal are not acceptable methods of contraception. Cessation of contraception after this point should be discussed with a responsible physician.
  • Agrees to abstain from breastfeeding during study participation and for at least 90 days after the last study drug administration.
  • A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time during the preceding 24 consecutive months).
  • Male patient must either practice true abstinence from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agrees to avoid fathering a child, to use highly effective methods of contraception, male condom plus spermicide during sexual contact with a pregnant female or a female of childbearing potential (even if he has undergone a successful vasectomy), from starting dose of drug (cycle 1 Day 1), including dose interruptions through 90 days after receipt of the last study drug administration. Furthermore, male patient must agree to not give semen or sperm during study drug therapy and for a period of 1 year after end of study drug therapy.
  • For EU countries, patient covered by a social security system

Who cannot join

  • 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
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  • 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.
  • Prior exposure to azacitidine and/ or any other demethylating agent (eg, decitabine)
  • Prior exposure to planned study treatment investigator's choice therapy (eg, prior exposure to gemcitabine is an exclusion if gemcitabine is the investigator's choice therapy prior to randomization)
  • Concurrent use of corticosteroids unless the patient is on a stable or decreasing dose for ≥ 1 week prior to informed consent form signature
  • Knowing or suspected hypersensitivity to active substance or to any of the excipients.
  • Pregnant, planning to become pregnant, or lactating woman
  • Candidate for hematopoietic stem cell transplantation
  • History of active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis), celiac disease (ie, 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 oral azacitidine and/or predispose the patient to an increased risk of gastrointestinal toxicity per investigator's decision. Any condition causing inability to swallow tablets.
  • Significant active cardiac disease within the previous 6 months, including:
  • New York Heart Association (NYHA) class IV congestive heart failure
  • Unstable angina or angina requiring surgical or medical intervention; and/or
  • Myocardial infarction
  • Person deprived of his/her liberty by a judicial or administrative decision
  • Adult person under legal protection

Trial locations and contacts

27 sites in 5 countries.

27 sites in 5 countries

France17 sites

  • Institut d'Hématologie de Basse Normandie

    Caen

  • CHU de Clermont-Ferrand - Hôpital Estaing

    Clermont-Ferrand

  • CHU Henri Mondor

    Créteil

  • CHU de Dijon

    Dijon

  • CHU de Grenoble

    Grenoble

  • CHRU de Lille

    Lille

  • CHU de Montpellier - Hôpital Saint-Eloi

    Montpellier

  • CHU de Nantes - Hôtel Dieu

    Nantes

  • Hôpital Necker

    Paris

  • Hôpital Saint-Louis

    Paris

  • CHU Haut-Lévèque - Centre François Magendie

    Pessac

  • CHU Lyon-Sud

    Pierre-Bénite

  • CH Annecy Genevois

    Pringy

  • CHU Pontchaillou

    Rennes

  • Centre Henri Becquerel

    Rouen

  • IUCT - Oncopole

    Toulouse

  • CHRU de Nancy - Hôpital de Brabois

    Vandœuvre-lès-Nancy

Other trials in France

United Kingdom4 sites

  • University College London Hospital

    London

  • The Christie

    Manchester

  • Nottingham City Hospital

    Nottingham

  • Churchill Hospital

    Oxford

Other trials in United Kingdom

Belgium3 sites

  • A. Z. Sint-Jan Brugge-Oostende AV

    Bruges

  • Cliniques Universitaires de Bruxelles - Hôpital Erasme

    Brussels

  • CHU UCL Namur - Site Godinne

    Yvoir

Other trials in Belgium

Austria2 sites

  • University Hospital for Internal Medicine - University Hospital Graz

    Graz

  • Medical University of Vienna

    Vienna

Other trials in Austria

Denmark1 site

  • Aarhus University Hospital

    Aarhus

Other trials in Denmark

About this study

Official title: Randomized Phase 3 Study Evaluating the Efficacy and the Safety of Oral Azacitidine (CC-486) Compared to Investigator's Choice Therapy in Patient With Relapsed or Refractory Angioimmunoblastic T Cell Lymphoma

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.

Read the detailed description

Compared to B-cell Non-Hodgin Lymphoma (NHL), Angioimmunoblastic T-cell Lymphoma (AITL) is more resistant to conventional chemotherapy and is generally associated with an inferior outcome. In case of relapsed of refractory disease, survival durations are in the range of only a few months.

Several agents have been evaluated in this setting in recent years: romidepsin, bendamustine or belinostat. The response rate with these agents rarely exceeds 30% and responses are usually of limited duration.

Azacitidine is a nucleoside metabolic inhibitor indicated for the treatment of patients with various myelodysplastic syndrome (MDS) subtypes. In this case, azacitidine significantly increase the survival time compared to standard of care option. This response to azacitidine could be correlated to the existence of recurrent mutations and those mutations have also been described in AITL.

The present protocol will use Azacitidine according to the same schedule than in MDS that is continuous treatment until progression or unacceptable toxicity.

Being tested
Oral azacitidine, Romidepsin, Bendamustine, Gemcitabine
Keywords
oral azacitidine
Medical subject headings
Immunoblastic Lymphadenopathy

What participants receive

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

  • Oral azacitidineDrug

    Also called CC-486

    Azacitidine tablets

  • RomidepsinDrug

    Also called Istodax

    Romidepsin injection

  • BendamustineDrug

    Also called Levact

    Bendamustine injection

  • GemcitabineDrug

    Also called Gemzar

    Gemcitabine injection

Study groups in NCT03593018
Study groupRoleWhat they receive
Oral AzacitidineExperimentalOral 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)
Receives: Drug: Oral azacitidine
Investigator's choice therapyActive comparatorRomidepsin 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)
Receives: Drug: Romidepsin; Drug: Bendamustine; Drug: Gemcitabine

What is being measured

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

  1. Progression Free Survival (PFS)

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

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

  2. Progression Free Survival (PFS)

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

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

Secondary outcomes (9)

  1. Overall survival (OS)

    Overall survival

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

  2. PFS by the Independent Review Committee (IRC)

    PFS by the Independent Review Committee

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

  3. Overall response rate

    Percentage of Complete Response (CR)+ Partial Response (PR) among all patients

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

  4. Complete response rate (CRR)

    Percentage of CR among all patients

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

  5. Duration of response (DoR)

    Duration of response

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

  6. Time to response (TtR)

    Time to response

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

  7. PFS 2 using local assessment of progressive disease

    PFS 2 using local assessment of progressive disease

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

  8. Quality of Life Questionnaire (QLQ-C30)

    questionnaire at baseline and at least one follow-up

    Measured: 2 years after last randomisation

  9. Number of Serious Adverse Events (SAE)

    Treatment discontinuation, adverse events, deaths

    Measured: 2 years after last randomisation

Timeline

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

  1. First posted19 Jul 2018
  2. Study start9 Nov 2018
  3. Primary completion10 Feb 2021
  4. Study completion28 Aug 2025

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
86 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03593018
Sponsor's protocol ID
ORACLE
Status last verified
Apr 2026
First submitted
6 Jul 2018
Last updated
23 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 38796193

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Oral azacitidine, Romidepsin and Bendamustine in people with Relapsed Angioimmunoblastic T-Cell Lymphoma and Refractory Angioimmunoblastic T-cell Lymphoma, run by The Lymphoma Academic Research Organisation at 27 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in France, United Kingdom, Belgium, Austria, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) (time frame: 18 months after first randomisation (when 18 events will occur)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03593018, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2026; AzTrials last refreshed its copy on 8 Nov 2026.

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