EUCTR2014-002675-29-ITActive, not recruitingPhase 1
A Phase 2, International, Multicenter, Randomized, Open-label, Parallel Group Study to Evaluate the Efficacy and Safety of CC-486 (oral azacitidine) Alone and in Combination with Durvalumab (MEDI4736) in Subjects With Myelodysplastic Syndromes Who Fail to Achieve an ObjectiveResponse to Treatment With Azacitidine for Injection or Decitabine - CC-486-MDS-006
CELGENE CORPORATIO0 sites194 target enrollmentStarted: June 18, 2021Last updated:
Conditions
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- Enrollment
- 194
Study Overview
Brief Summary
No summary available.
Study Design
- Study Type
- Interventional clinical trial of medicinal product
Eligibility Criteria
- Sex
- All
Inclusion Criteria
- •1. Male or female, = 18 years of age at the time of signing the ICD.
- •2. Documented diagnosis of myelodysplastic syndromes (MDS),classified according to French-American British (FAB) cooperation group classification criteria.
- •3. Adequate course of treatment with an injectable hypomethylating agent (azacitidine for injection or decitabine) as the last therapeutic intervention for myelodysplastic syndromes prior to beginning screening for this study.
- •4. Documented disease progression or stable disease as best response to treatment (or attempted treatment) with azacitidine for injection or
- •decitabine. Those achieving an objective response to the treatment regimen with an injectable HMA are excluded from participation in this study.
- •5. Have the last dose of the prior treatment regimen (injectable hypomethylating agent (HMA) – azacitidine for injection or decitabine) not more than 16 weeks prior to screening for this study.
- •6. No less than 3 weeks between the last dose of the prior treatment regimen (injectable HMA – azacitidine for injection or decitabine) and the planned date of first dose of investigative product.
- •7. Have an Eastern Oncology Cooperative Group (ECOG) performance status of 0, 1, or 2.
- •8. Females subjects of childbearing potential may participate, providing they meet the following conditions:
- •a) have two negative pregnancy test s as verified by the investigator prior to starting any IP therapy; serum pregnancy test at screening; and negative serum or urine pregnancy test within 72 hours prior to starting treatment with IP. 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 practice true 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 highly effective methods 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 last dose of IP.
- •d) Refrain from egg cell donation while taking duravlumab and for at least 90 days after the last dose of durvalumab.
- •9.Male subjects 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, male condom plus spermicide during sexual contact with a pregnant female or female of child bearing potential (even if he has undergone a successful vasectomy) from starting dose IP (Cycle 1 Day) including dose interruption 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.
- •10.Understand and voluntarily sign an informed consent document prior to any study- related assessments or procedures conducted.
- •11.Understand and voluntarily sign a biomarker-specific component of the informed consent document prior to any study-related procedures
- •12.Be able to adhere to the study visit sche
Exclusion Criteria
- •1. Rapidly-progressing MDS
- •2. AML-FAB classification: =30% blasts in bone marrow). Subjects known to have =30% blasts are not eligible for inclusion in this study.Recognizing limitations of blast cell quantification, this protocol will allow subjects with pre-enrollment (screening/baseline) bone marrow blast counts up to 33% to be considered for inclusion.
- •3. Prior allogeneic stem cell transplant.
- •4. Prior exposure to the investigational oral formulation of decitabine, or other oral azacitidine derivative at any time in the subjects prior history
- •5. Prior or ongoing response (IWG 2006: HI, PR,CR, or marrow CR) to treatment with azacitidine for injection or decitabine, at any time in the subjects prior history, which includes relapsed disease.
- •7. Use of any of the following within 28 days prior to the first dose of IP:
- •a)thrombopoiesis-stimulating agents ([TSAs]; eg, Romiplostim, Eltrombopag, Interleukin-11)
- •b)ESAs and other RBC hematopoietic growth factors (eg, Interleukin-3)
- •c)hydroxyurea
- •8. Concurrent use of corticosteroids unless the subject is on a stable or decreasing dose for =1 week prior to enrollment for medical conditions
- •other than MDS
- •9. History of 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 IP and/or predispose the subject to an increased risk of gastrointestinal toxicity.
- •10. Prior history of malignancies, other than MDS, unless the subject has been free of the disease for = 3 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 [TNM] clinical staging system)
- •11. Significant active cardiac disease within the previous 6 months
- •12. Uncontrolled systemic fungal, bacterial, or viral infection (ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment)
- •13. Known HIV or HCV infection, or evidence of active HBV infection
- •14. Any of the following laboratory abnormalities:
- •- Serum AST/SGOT or ALT/SGPT > 2.5 x ULN
- •- Serum total bilirubin > 1.5 x ULN. Higher levels are acceptable if these can be attributed to active red blood cell precursor destruction within
- •the bone marrow (ie, ineffective erythropoiesis). Subjects are excluded if there is evidence of autoimmune hemolytic anemia manifested as a
- •corrected reticulocyte count of > 2% with either a positive Coombs' test or over 50% of indirect bilirubin
- •- Serum creatinine > 2.5 x ULN
- •- Absolute WBC count = 20 x 10*9/L
- •15. Known or suspected hypersensitivity to azacitidine or mannitol, or durvalumab its constituents, or to any other humanized monoclonal antibody
- •16. Pregnant planning to become pregnant starting from 28 days prior to receiving CC-486 or durvalumab, throughout your participation in the study, and for at least 90 days following your last dose of study treatment or breast-feeding females
- •17. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
- •18. Any condition including the presence of laboratory abnormalities,which places the
Investigators
Similar Trials
Active, not recruiting
Phase 1
A Phase 2 Global Study conducted to see the benefit and safety of CC-486 alone and in combination with Durvalumab (MEDI4736) in patients with Myelodysplastic Syndromes who Did Not Respond to Treatment With Azacitidine for injection or Decitabine.Myelodysplastic syndrome (MDS)MedDRA version: 20.0Level: LLTClassification code 10068361Term: MDSSystem Organ Class: 100000004864EUCTR2014-002675-29-PLCelgene Corporation194
Active, not recruiting
Phase 1
A Phase 2 Global Study conducted to see the benefit and safety of CC-486 alone and in combination with Durvalumab (MEDI4736) in patients with Myelodysplastic Syndromes who Did Not Respond to Treatment With Azacitidine for injection or Decitabine.Myelodysplastic syndrome (MDS)MedDRA version: 18.1Level: LLTClassification code 10068361Term: MDSSystem Organ Class: 100000004864EUCTR2014-002675-29-ESCelgene Corporation194
Active, not recruiting
Phase 1
A Phase 2 Global Study conducted to see the benefit and safety of CC-486 alone and in combination with Durvalumab (MEDI4736) in patients with Myelodysplastic Syndromes who Did Not Respond to Treatment With Azacitidine for injection or Decitabine.Myelodysplastic syndrome (MDS)MedDRA version: 20.0Level: LLTClassification code 10068361Term: MDSSystem Organ Class: 100000004864EUCTR2014-002675-29-GBCelgene Corporation194
Active, not recruiting
Phase 1
A study to evaluate efficacy and safety of SAR441566 in adults with plaque psoriasisPsoriasisMedDRA version: 20.0Level: PTClassification code: 10037153Term: Psoriasis Class: 100000004858CTIS2023-503911-14-00Sanofi-Aventis Research & Development490
Recruiting
Phase 2
A study to evaluate efficacy and safety of SAR441566 in adults with plaque psoriasisPsoriasisJPRN-jRCT2061230086Tanaka Tomoyuki207