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This is a multicenter, open-label, Phase 1 study to assess the safety and antitumor activity of MEDI4736 as Monotherapy or in Combination with Tremelimumab with or without Azacitidine in Subjects with myelodysplastic syndrome after treatment with hypomethylating agents
A dose-escalation and dose-expansion study of MEDI4736 (a monoclonal antibody that targets programmed cell death-1 ligand 1 [PD-L1]) to evaluate the safety, tolerability, PK, IM, and antitumor activity of MEDI4736 as monotherapy or in combination with Tremelimumab with or without Azacitidine in adult patients with myelodysplastic syndrome.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MEDI4736 Evaluate MEDI4736 in MDS | Experimental | Evaluate MEDI4736 monotherapy and MEDI4736 in combination with azacitidine after monotherapy progression in MDS |
|
| MEDI4736 + tremelimumab | Experimental | Evaluate MEDI4736 in combination with tremelimumab |
|
| MEDI4736 + tremelimumab + azacitidine | Experimental | Evaluate MEDI4736 in combination with tremelimumab and azacitidine |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MEDI4736 Evaluate MEDI4736 in MDS | Biological | MEDI4736 will be administered by IV infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Subject's safety where no more than one out of six subjects experience DLTs at a given dose | DLT (MEDI4736 monotherapy only) assessment will be done by reviewing adverse events (AEs), serious adverse events (SAEs), laboratory evaluations, vital signs, physical examinations, and electrocardiogram (ECG) results. For monotherapy or combo w/aza AEs, SAEs, lab evaluations, vital signs, physical exams, ECGs will be done. | 180 days |
| Subject's safety overall (monotherapy and combination therapies) | Overall safety assessments will be done by reviewing adverse events (AEs, serious adverse events (SAEs), laboratory evaluations, vital signs, physical examinations and electrocardiogram (ECG) results. | 730 days |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical outcome in terms of response: duration of response | As defined by IWG 2006 MDS response criteria | 2 years |
| Clinical outcome in terms of response: transfusion requirements | As defined by IWG 2006 MDS response criteria and incidence of transfusions. |
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Inclusion Criteria:
Adult male or female subjects with pathologically confirmed MDS who failed to respond, relapsed after an initial response, or were unable to tolerate hypomethylating agents, ECOG performance status of 0 - 2, and adequate organ and marrow function.
Exclusion Criteria:
Concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment, prior MAb against CTLA-4, PD-1, or PD-L1, alllogenic or haploidentical transplant, current immunosuppressive medication or autoimmune or inflammatory disease.
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| Name | Affiliation | Role |
|---|---|---|
| MedImmune LLC | MedImmune LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Scottsdale | Arizona | 85259 | United States | ||
| Research Site |
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| VIDAZA | Drug | VIDAZA will be administered subcutaneously as described on the package insert VIDAZA will be administered in combination with MEDI4736 upon progression from MEDI4736 monotherapy |
|
|
| tremelimumab | Biological | tremelimumab will be administered by IV infusion |
|
| 2 years |
| Clinical outcome in terms of response: progression-free survival (PFS) | As defined by IWG 2006 MDS response criteria | 2 years |
| Clinical outcome in terms of response: survival (OS) | As defined by IWG 2006 MDS response criteria and collection of survival data | 2 years |
| Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: peak concentration | Peak concentration of MEDI4736 and tremelimumab in serum | 1 year |
| Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: area under the concentration-time curve | Analysis of area under the concentration-time curve | 1 year |
| Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: clearance | Rate of MEDI4736 and tremelimumab clearance | 1 year |
| Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: terminal half-life | MEDI4736 and tremelimumab concentration terminal half-life | 1 year |
| Immunogenicity | Determine by number of subjects who develop ADA (anti-drug antibody). | 1 year |
| Health-related quality of life (QOL): disease- and treatment-related symptoms (Part 1 only) | Analysis of reporting of disease- and treatment-related symptoms (Part 1 only) | 2 years |
| Health-related quality of life (QOL): pain (Part 1 only) | Analysis of incidence of pain reporting (Part 1 only) | 2 years |
| Health-related quality of life (QOL): health status (Part 1 only) | Analysis of reporting of health status. (Part 1 only) | 2 years |
| Los Angeles |
| California |
| 90095 |
| United States |
| Research Site | New Haven | Connecticut | 06520-8063 | United States |
| Research Site | Tampa | Florida | 33612 | United States |
| Research Site | Atlanta | Georgia | 30322 | United States |
| Research Site | Chicago | Illinois | 60637 | United States |
| Research Site | Baltimore | Maryland | 21201 | United States |
| Research Site | Boston | Massachusetts | 02215 | United States |
| Research Site | Detroit | Michigan | 48201 | United States |
| Research Site | Rochester | Minnesota | 55905 | United States |
| Research Site | New York | New York | 10029 | United States |
| Research Site | New York | New York | 10065 | United States |
| Research Site | Greenville | South Carolina | 29601 | United States |
| Research Site | Houston | Texas | 77030 | United States |
| Research Site | San Antonio | Texas | 78229 | United States |
| Research Site | Milwaukee | Wisconsin | 53226 | United States |
| Research Site | Paris | 75475 | France |
| Research Site | Dresden | 1307 | Germany |
| Research Site | Brighton | BN2 5BE | United Kingdom |
| Research Site | London | SE5 9RS | United Kingdom |
| Research Site | Manchester | M20 4BX | United Kingdom |
| ID | Term |
|---|---|
| D009190 | Myelodysplastic Syndromes |
| ID | Term |
|---|---|
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C000613593 | durvalumab |
| D001374 | Azacitidine |
| C520704 | tremelimumab |
| ID | Term |
|---|---|
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
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