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A Randomized Multicenter, Open-label, Phase 2 Study Evaluating the Efficacy and Safety of Azacitidine Subcutaneous in Combination With Durvalumab (MEDI4736) in Previously Untreated Subjects with Higher-Risk Myelodysplastic Syndromes (MDS) or in Elderly (>= 65 years) Acute Myeloid Leukemia (AML) Subjects Not Eligible for Hematopoietic Stem Cell Transplantation (HSCT).

Phase 2
Withdrawn
Conditions
MYELODYSPLASTIC SYNDROMES (MDS)
10035227
10024324
Registration Number
NL-OMON46021
Lead Sponsor
Celgene Corporation
Brief Summary

Trial never started

Detailed Description

Not available

Recruitment & Eligibility

Status
Withdrawn
Sex
Not specified
Target Recruitment
40
Inclusion Criteria

For both cohorts:
1. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
2. Have an ECOG performance status of 0, 1, or 2 (Appendix E).
3. Female subjects of childbearing potential may participate, providing they meet the following conditions:
a. Have 2 negative pregnancy tests as verified by the Investigator prior to starting any 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.
b. 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 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 for 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.
c. Agree to abstain from breastfeeding during study participation and for at least 90 days after the last dose of IP.
d. Refrain from egg cell donation while taking durvalumab and for at least 90 days after the last dose of durvalumab.
4. Male subject must:
a. 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, to use 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.
b. Refrain from semen or sperm donation while taking IP and for at least 90 days after the last dose of IP.;More inclusion criteria can found in the protocol version 17Nov2015 on page 47.

Exclusion Criteria

For both cohorts:
1. Prior hematopoietic stem cell transplant.
2. Considered eligible for hematopoietic stem cell transplant (allogeneic or autologous) at the time of signing the ICF.
3. Prior exposure to azacitidine, decitabine or prior exposure to the investigational oral formulation of decitabine, or other oral azacitidine derivative.
4. Inaspirable bone marrow.
5. 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 (ESAs and other RBC hematopoietic growth factors (eg, Interleukin-3)
· Any investigational agents within 28 days or 5 half-lives (whichever is longer) of initiating study treatment ;More exclusion criteria can found in the current protocol version, and clinical trial application form.

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
<p>The primary objective of the study is to evaluate the efficacy of subcutaneous<br /><br>azacitidine in combination<br /><br>with durvalumab as compared with subcutaneous azacitidine alone in the defined<br /><br>study population.</p><br>
Secondary Outcome Measures
NameTimeMethod
<p>. Assess the safety and tolerability of subcutaneous azacitidine in<br /><br>combination with<br /><br>durvalumab as compared with subcutaneous azacitidine alone in the defined study<br /><br>population<br /><br>. Assess the pharmacokinetics (PK) of durvalumab when given in combination with<br /><br>subcutaneous azacitidine in the defined study population.</p><br>
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