A study to evaluate the safety and efficacy of the combination of durvalumab with azacitidine to treat a cancer of the bone marrow, causing cancer cell proliferation and improper normal blood cell production.
- Conditions
- Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML)MedDRA version: 18.1Level: HLTClassification code 10028536Term: Myelodysplastic syndromesSystem Organ Class: 100000004851Therapeutic area: Diseases [C] - Cancer [C04]MedDRA version: 18.1Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 100000004864
- Registration Number
- EUCTR2015-003596-30-ES
- Lead Sponsor
- Celgene International II Sàrl
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 182
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.
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 use at least two effective methods of contraception (eg, oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; true abstinence; or vasectomized partner) 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 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 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.
5. Understand and voluntarily sign a biomarker-specific component of the informed consent form prior to any study-related procedures conducted.
6. Willing and able to adhere to the study visit schedule and other protocol requirements.
MDS Cohort:
7. Age ? 18 years at the time of signing the informed consent form.
8. Central confirmation of diagnosis of previously untreated primary or secondary MDS as per WHO classification. Results of central pathology review are required prior to receiving the first dose of IP.
9. Central confirmation of the categorization of the MDS risk classification, as per the 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).
AML Cohort:
10. Age ? 65 years at the time of signing the informed consent form (ICF).
11. 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 therapie
For both cohorts:
1. Prior hematopoietic stem cell transplant.
2. Considered eligible for hematopoietic stem cell transplant (allogeneic or autologous).
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
· Any hematopoietic growth factors
· Any investigational agents within 28 days or 5 half-lives (whichever is longer) of initiating study treatment
6. 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.
7. Pregnant or breast-feeding females or females who intend to become pregnant during study participation.
8. Subject has active or prior documented autoimmune or inflammatory disorders 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 stable on hormone replacement for ? 3 months prior to signing the ICF; or
· Subjects with psoriasis not requiring systemic treatment
9. Significant active cardiac disease within the previous 6 months prior to signing the ICF
10. Uncontrolled intercurrent illness.
11. Known HIV or HCV infection, or evidence of active HBV infection.
12.Known or suspected hypersensitivity to azacitidine, mannitol, or durvalumab, its constituents, or to any other humanized mAb.
13. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
14. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
15. Prior anti-CTLA-4, PD-1, or PD-L1 or other immune checkpoint mAb exposure.
16. Other investigational mAbs within 6 months prior to first dose of IP.
17. Current or prior use of immunosuppressive medication within 14 days prior to the first dose of IP. The following are exceptions:
· Intranasal, inhaled, topical, or local steroid injections
· Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
· Steroids as premedication for hypersensitivity reactions
18. History of primary immunodeficiency.
19. Receipt of live, attenuated vaccine within 30 days prior to the first dose of IP.
20. Unwilling or unable to complete subject reported outcome assessments without assistance or with minimal assistance from trained site personnel and/or caregiver.
21. Subjects who have had clinical evidence of CNS or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia.
22. Presence of advanced malignant hepatic tumors.
23. Any of the following laboratory abnormalities:
· AST/SGOT or ALT/SGPT > 2.5 × ULN
· Serum total bilirubin > 1.5 × ULN. Higher levels are acceptable if these can be attributed to active red blood cell precursor destruction within the bone marrow. Subjects are excluded if there is evidence of autoimmune hemolytic anemia manifested as a corrected reticulocyte count of > 2% with either a positive Coombs?
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method