Ignite Creation Date:
2025-12-24 @ 12:41 PM
Ignite Modification Date:
2026-01-04 @ 9:04 AM
Study NCT ID:
NCT02953561
Status:
TERMINATED
Last Update Posted:
2020-10-22
First Post:
2016-11-01
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Avelumab and Azacitidine in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia
Sponsor:
M.D. Anderson Cancer Center
Organization:
Study Overview
Official Title:
An Open-Label Phase Ib/II Study of Avelumab in Combination With 5-Azacytidine (Vidaza) for the Treatment of Patients With Refractory/Relapsed Acute Myeloid Leukemia
Status:
TERMINATED
Status Verified Date:
2020-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
PDOL request
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase Ib/II trial studies the best dose and side effects of avelumab when given together with azacitidine and to see how well they work in treating patients with acute myeloid leukemia that is not responding to treatment or has come back. Monoclonal antibodies, such as avelumab, may interfere with the ability of cancer cells to grow and spread. Azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving avelumab and azacitidine may work better in treating patients with acute myeloid leukemia.
Detailed Description:
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of avelumab in combination with azacitidine (5-azacytidine) in patients with refractory/relapsed acute myeloid leukemia (AML). (Phase IB)
II. To determine the overall response rate (ORR) defined as complete remission (CR)/complete remission with incomplete platelet recovery (CRp)/complete remission with incomplete count recovery (CRi)/partial remission (PR)/hematologic improvement (HI)/morphologic leukemia free state (MLFS) of avelumab in combination with 5-azacytidine in patients with refractory/relapsed AML. (Phase II
SECONDARY OBJECTIVES:
I. To determine the number of patients achieve \> 50% reduction in blasts on therapy with this combination.
II. To determine the duration of response, disease-free survival (DFS), and overall survival (OS) of patients with refractory/relapsed AML treated with this combination
TERTIARY OBJECTIVES:
I. To study immunological and molecular features at baseline and at predefined time-points on-therapy with avelumab and azacytidine in the peripheral blood and bone marrow to include quantify immune ligand expression by the AML blasts and AML stromal components (myeloid-derived suppressor cells \[MDSCs\] and mesenchymal stem cells \[MSCs\]) including 4-1BBL, ICOSL, PD-L1, PD-L2, OX-40L, CD137L.
II. To study immunological and molecular features at baseline and at predefined time-points on-therapy with avelumab and azacytidine in the peripheral blood and bone marrow to determine the quantitative expression of positive and negative co-stimulatory molecules on individual T-lymphocyte subsets including 4-1BB, CTLA-4, ICOS, PD-1, OX40, LAG-3 and TIM-3.
III. To study immunological and molecular features at baseline and at predefined time-points on-therapy with avelumab and azacytidine in the peripheral blood and bone marrow to identify the immunophenotype of tumor-infiltrating T-lymphocytes (TILs) pre- and post-therapy with the combination: CD8+, CD4+ effector, or CD4+ regulatory.
IV. To develop a micro-array based gene expression profile (GEP) predictor of response to anti-PDL1 and epigenetic therapy in AML.
V. To determine the correlation of responses to the combination with baseline cytogenetic and molecular abnormalities
OUTLINE: This is a phase Ib, dose-escalation study of avelumab followed by a phase II study
Patients receive azacitidine subcutaneously (SC) or intravenously (IV) over 10-40 minutes on days 1-7 or on days 1-5 and 8-9. Patients also receive avelumab IV over 60 minutes on days 1 and 14 for 4 courses (or until complete response) and on day 1 for subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
After completion of study treatment, patients are followed up every 3-6 months for up to 5 years.
I. To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of avelumab in combination with azacitidine (5-azacytidine) in patients with refractory/relapsed acute myeloid leukemia (AML). (Phase IB)
II. To determine the overall response rate (ORR) defined as complete remission (CR)/complete remission with incomplete platelet recovery (CRp)/complete remission with incomplete count recovery (CRi)/partial remission (PR)/hematologic improvement (HI)/morphologic leukemia free state (MLFS) of avelumab in combination with 5-azacytidine in patients with refractory/relapsed AML. (Phase II
SECONDARY OBJECTIVES:
I. To determine the number of patients achieve \> 50% reduction in blasts on therapy with this combination.
II. To determine the duration of response, disease-free survival (DFS), and overall survival (OS) of patients with refractory/relapsed AML treated with this combination
TERTIARY OBJECTIVES:
I. To study immunological and molecular features at baseline and at predefined time-points on-therapy with avelumab and azacytidine in the peripheral blood and bone marrow to include quantify immune ligand expression by the AML blasts and AML stromal components (myeloid-derived suppressor cells \[MDSCs\] and mesenchymal stem cells \[MSCs\]) including 4-1BBL, ICOSL, PD-L1, PD-L2, OX-40L, CD137L.
II. To study immunological and molecular features at baseline and at predefined time-points on-therapy with avelumab and azacytidine in the peripheral blood and bone marrow to determine the quantitative expression of positive and negative co-stimulatory molecules on individual T-lymphocyte subsets including 4-1BB, CTLA-4, ICOS, PD-1, OX40, LAG-3 and TIM-3.
III. To study immunological and molecular features at baseline and at predefined time-points on-therapy with avelumab and azacytidine in the peripheral blood and bone marrow to identify the immunophenotype of tumor-infiltrating T-lymphocytes (TILs) pre- and post-therapy with the combination: CD8+, CD4+ effector, or CD4+ regulatory.
IV. To develop a micro-array based gene expression profile (GEP) predictor of response to anti-PDL1 and epigenetic therapy in AML.
V. To determine the correlation of responses to the combination with baseline cytogenetic and molecular abnormalities
OUTLINE: This is a phase Ib, dose-escalation study of avelumab followed by a phase II study
Patients receive azacitidine subcutaneously (SC) or intravenously (IV) over 10-40 minutes on days 1-7 or on days 1-5 and 8-9. Patients also receive avelumab IV over 60 minutes on days 1 and 14 for 4 courses (or until complete response) and on day 1 for subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
After completion of study treatment, patients are followed up every 3-6 months for up to 5 years.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2016-01924 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| 2016-0444 | OTHER | M D Anderson Cancer Center | View | |
| P30CA016672 | NIH | None | https://reporter.nih.gov/quic… | View |