Efficacy and Safety of Oral Azacitidine (CC-486) Compared to Investigator's Choice Therapy in Patients With Relapsed or Refractory Angioimmunoblastic T Cell Lymphoma

NCT03703375 | Active Not Recruiting Phase 3 Results DMC

• 2 other identifiers: OA-CL-LYM-LYSARC-13134CU1111-1220-8294
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 12

Brief Summary

This study is a multicentric, open-label, randomized phase 3 trial. The study will be conducted in select countries in Europe and South Korea sponsored by LYSARC and in Japan sponsored by Celgene. There will be a combined enrollment target of 86 randomized patients, with approximately 14 randomized patients from Japan. The enrollment to the randomized study will start at European sites in parallel to a safety run-in part in Japan. A safety run-in will be conducted to confirm the tolerability of oral azacitidine at doses of 100 mg and 200 mg QD in Asian patients. Once oral azacitidine at 200 mg QD is confirmed as tolerable, Asian patients from Japan and South Korea will start to be randomized into the main study. Additional patients (non-randomized) are anticipated to enroll to the safety run-in.

Conditions

Lymphoma, T-Cell

Keywords

CC-486; Azacitidine; Angioimmunoblastic; T Cell Lymphoma; Lymphoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) Based on Local Assessment

  PFS is defined as the time from randomization into the study to the first observation of documented disease progression (local assessment using Lugano Response Criteria 2014) or death due to any cause, whichever occurs first. If a participant has not progressed or died, PFS will be censored at the time of last visit with adequate assessment. C2 censoring rules were used per US FDA guidance 2015. Progression will be determined as per Response criteria for lymphoma: Lugano classification.

  From randomization up to documented disease progression or death, whichever occurs first (up to approximately 15 months)

Secondary Outcomes (8)

• Overall Survival (OS)

  From randomization up to the date of death or date last known alive (up to approximately 27 months)

• Progression Free Survival (PFS) Based on IRC Assessment

  From randomization up to documented disease progression or death, whichever occurs first (up to approximately 37 months)

• Overall Response Rates (ORR)

  Response rate will be measured after Cycle 3, after Cycle 6 (up to approximately 5.5 months)

• Complete Response Rate (CRR)

  Response rate will be measured after Cycle 3, after Cycle 6 (up to approximately 5.5 months)

• Duration of Response (DOR)

  From randomization to the date of first documented disease progression, relapse (local assessment) or death from any cause (up to approximately 27 months)

Study Arms (3)

Administration of Oral Azacitidine (CC-486)

EXPERIMENTAL

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

Drug: Azacitidine

Investigator's choice therapy - Romidepsin

ACTIVE COMPARATOR

Romidepsin 14mg/m2 on days 1, 8 and 15 of a 28-days cycle (Treatment until progression, patient decision or toxicity)

Drug: Romidepsin

Investigator's choice therapy - Gemcitabine

ACTIVE COMPARATOR

Gemcitabine 1000mg/m2 on days 1, 8 and 15 of a 28-days cycle (during 6 cycles)

Drug: Gemcitabine

Interventions

Azacitidine DRUG

Azacitidine

Also known as: CC-486

Administration of Oral Azacitidine (CC-486)

Romidepsin DRUG

Romidepsin

Investigator's choice therapy - Romidepsin

Gemcitabine DRUG

Gemcitabine

Investigator's choice therapy - Gemcitabine

Eligibility Criteria

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

You may qualify if:

• 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 WHO classification based on a surgical lymph node biopsy or needle core 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.
• ECOG performance status 0 to 3
• Meet the following lab criteria:
• ANC ≥ 1,5 x 109/L (≥ 1 x 109/L if 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.

You may not qualify if:

• Clinical evidence of central nervous system(CNS) involvement by lymphoma. Patients with suspicion of 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 active Hepatitis B Virus (HBV) infection defined as:
• HBs Ag positive
• HBs Ag negative, anti-HBs antibody positive and/or anti-HBc antibody positive with detectable viral DNA
• Impaired renal function (calculated MDRD 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 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
• 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)
• Concurrent use of corticosteroids unless the patient is on a stable or decreasing dose for ≥ 1 week prior to informed consent form signature

Sponsors & Collaborators

• Celgene: lead

Study Sites (12)

Local Institution - 41822

Sapporo, Hokkaido, 0608648, Japan

Location

Local Institution - 41922

Okayama, Okayama-ken, 700-8558, Japan

Location

Local Institution - 41722

Sayama, Osaka, 5898511, Japan

Location

Local Institution - 41422

Hidaka, Saitama-Pref, 350-1298, Japan

Location

Local Institution - 40722

Chuo-ku, Tokyo, 104-0045, Japan

Location

Local Institution - 40222

Koto-ku, Tokyo, 1358550, Japan

Location

Local Institution - 40922

Fukuoka, 812-8582, Japan

Location

Local Institution - 40122

Isehara City, Kanagawa, 259-1193, Japan

Location

Local Institution - 41522

Kashiwa, 277-8577, Japan

Location

Local Institution - 41622

Nagoya, 460-0001, Japan

Location

Local Institution - 41222

Sendai, 980-8574, Japan

Location

Local Institution - 41322

Tsukuba, 305-8576, Japan

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

• BMS Clinical Trial Information

MeSH Terms

Conditions

Lymphoma, T-Cell; Lymphoma

Interventions

Azacitidine; cc-486; romidepsin; Gemcitabine

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; 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; Deoxycytidine

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

855-907-3286

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: October 9, 2018
• First Posted: October 12, 2018
• Study Start: November 6, 2018
• Primary Completion: February 10, 2021
• Study Completion: March 31, 2026
• Last Updated: July 8, 2024
• Results First Posted: July 8, 2024

Record last verified: 2024-07

Locations

JP (12)