An Efficacy and Safety Study of Azacitidine Subcutaneous in Combination With Durvalumab (MEDI4736) in Previously Untreated Adults With Higher-Risk Myelodysplastic Syndromes (MDS) or in Elderly Patients With Acute Myeloid Leukemia (AML)

Completed · Phase 2

Conditions studied: Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

In brief

The primary objective of this study is to evaluate the efficacy of subcutaneous azacitidine in combination with durvalumab as compared with subcutaneous azacitidine alone in adults with previously untreated, higher risk MDS who are not eligible for HSCT or in adults ≥ 65 years old with previously untreated AML who are not eligible for HSCT, with intermediate or poor cytogenetic risk.

Key facts

Study ID

NCT02775903

Run by

Celgene

People needed

213

Starts

2016-06-03

Expected to finish

2021-12-27

Last updated by the study team

2023-02-28

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• For both cohorts:
• Subject must understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessments/procedures being conducted.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Female subjects of childbearing potential may participate, providing they meet the following conditions:
• Have 2 negative pregnancy tests as verified by the Investigator prior to starting any investigational product (IP) therapy: serum pregnancy test at screening and negative serum or urine pregnancy test (Investigator's discretion) within 72 hours prior to starting treatment with IP (Cycle 1, Day 1). They must agree to ongoing pregnancy testing during the course of the study (before beginning each subsequent cycle of treatment), and after the last dose of any IP. This applies even if the subject practices complete abstinence from heterosexual contact.
• Agree to practice true abstinence (which must be reviewed on a monthly basis and source documented) or agree to the use of a highly effective method of contraception use from 28 days prior to starting durvalumab or azacitidine, and must agree to continue using such precautions while taking durvalumab or azacitidine (including dose interruptions) and up to 90 days after the last dose of durvalumab or azacitidine. Cessation of contraception after this point should be discussed with a responsible physician.
• Agree to abstain from breastfeeding during study participation and for at least 90 days after the last dose of IP.
• Refrain from egg cell donation while taking durvalumab and for at least 90 days after the last dose of durvalumab.
• Male subject must:
• Either practice true abstinence from heterosexual contact (which must be reviewed on a monthly basis) or agree 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 IP (Cycle 1 Day 1), including dose interruptions through 90 days after receipt of the last dose of durvalumab or azacitidine.
• Refrain from semen or sperm donation while taking IP and for at least 90 days after the last dose of IP.
• Understand and voluntarily sign a biomarker-specific component of the informed consent form prior to any study-related procedures conducted.
• Willing and able to adhere to the study visit schedule and other protocol requirements.
• MDS Cohort:
• Age ≥ 18 years at the time of signing the informed consent form.
• Central confirmation of diagnosis of previously untreated primary or secondary myelodysplastic syndromes (MDS) as per World Health Organization (WHO) classification. Results of central pathology review are required prior to receiving the first dose of IP.
• Central confirmation of the categorization of the MDS risk classification, as per the Revised - International prognostic scoring system (IPSS-R) Intermediate risk with >10% blasts or poor or very poor cytogenetics, or IPSS-R High or Very High risk (results of central pathology review required prior to receiving the first dose of IP).
• Acute myeloid leukemia (AML) Cohort:
• Age ≥ 65 years at the time of signing the informed consent form (ICF).
• Central confirmation of diagnosis of one of the following untreated AML as per WHO classification:
• Newly diagnosed, histologically confirmed de novo AML (bone marrow blasts ≥ 20%), or
• AML secondary to prior MDS, or
• AML secondary to exposure to potentially leukemogenic therapies or agents (eg, radiation therapy, alkylating agents, topoisomerase II inhibitors) with the primary malignancy in remission for at least 2 years.
• Central confirmation of intermediate or poor risk status, based on Cytogenetics for acute myeloid leukemia.

You may not qualify if…

• For both cohorts:
• Prior hematopoietic stem cell transplant.
• Considered eligible for hematopoietic stem cell transplant (allogeneic or autologous) at the time of signing the ICF.
• Prior exposure to azacitidine, decitabine or prior exposure to the investigational oral formulation of decitabine, or other oral azacitidine derivative.
• Inaspirable bone marrow.
• Use of any of the following within 28 days prior to the first dose of IP:
• Thrombopoiesis-stimulating agents (eg, romiplostim, eltrombopag, Interleukin-11)
• Any hematopoietic growth factors (erythropoietin-stimulating agents [ESAs], granulocyte colony-stimulating factor (G-CSF) and other red blood cell (RBC) hematopoietic growth factors (eg, Interleukin-3)
• Any investigational agents within 28 days or 5 half-lives (whichever is longer) of initiating study treatment
• Prior history of malignancies (except MDS for AML subjects), unless the subject has been free of the disease for ≥ 2 years. However, subjects 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 [tumor, node, metastases (TNM)] clinical staging system).
• Pregnant or breast-feeding females or females who intend to become pregnant during study participation.
• Subject has active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis, Crohn's disease], diverticulitis with the exception of a prior episode that has resolved or diverticulosis, celiac disease, irritable bowel disease [exclude only if active within the last 6 months prior to signing the ICF], or other serious gastrointestinal chronic conditions associated with diarrhea; systemic lupus erythematosus; Wegener's syndrome [granulomatosis with polyangiitis]; myasthenia gravis; Graves' disease; rheumatoid arthritis; hypophysitis, uveitis; etc) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
• Subjects with vitiligo or alopecia;
• Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement for ≥ 3 months prior to signing the ICF; or
• Subjects with psoriasis not requiring systemic treatment
• Significant active cardiac disease within the previous 6 months prior to signing the ICF, including:
• New York Heart Association (NYHA) Class III or IV congestive heart failure;
• Unstable angina or angina requiring surgical or medical intervention; and/or
• Significant cardiac arrhythmia
• Myocardial infarction
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment), uncontrolled hypertension, cardiac arrhythmia, pneumonitis, interstitial lung disease, active peptic ulcer disease or gastritis that would limit compliance with study requirement.

Where it is running

• Georgetown University Hospital — Washington D.C., District of Columbia, United States
• University of Florida — Gainesville, Florida, United States
• Moffitt Cancer Center — Tampa, Florida, United States
• University of Chicago — Chicago, Illinois, United States
• Hackensack University Medical Center — Hackensack, New Jersey, United States
• Roswell Park Cancer Institute — Buffalo, New York, United States
• Icahn School of Medicine at Mount Sinai — New York, New York, United States
• Duke University Medical Center — Durham, North Carolina, United States
• Avera Cancer Institute — Sioux Falls, South Dakota, United States
• Vanderbilt University Medical Center — Nashville, Tennessee, United States
• University of Texas- MD Anderson — Houston, Texas, United States
• Medizinische Universitat Graz — Graz, Austria
• Medizinische Universitat Innsbruck — Innsbruck, Austria
• Elisabethinen Hospital Linz — Linz, Austria
• Salzburger Landkliniken St. Johanns-Spital — Salzburg, Austria
• Hanusch Krankenhaus der Stadt Wien — Vienna, Austria
• Local Institution - 653 — Vienna, Austria
• AKH Wien — Wein, Austria
• Cliniques Universitaires St-Luc — Brussels, Belgium
• Grand Hopital de Charleroi — Charleroi, Belgium
• Local Institution - 202 — Ghent, Belgium
• UH Gent — Ghent, Belgium
• UH Gasthuisberg — Leuven, Belgium
• Cliniques Universitaires UCL de Mont-Godine — Yvoir, Belgium
• Yale Cancer Center — New Haven, Connecticut, United States

Full record on ClinicalTrials.gov

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