Phase 2 AML Clinical Trial - currently recruiting
Status: |
Recruiting Patients |
Title: |
A Phase 2 Trial of the MUC1-C inhibitor, GO-203 in combination with decitabine in patients with acute myeloid leukemia |
Study Design: |
Patients will receive GO-203 at a dose of 18 mg/m2 intravenously over 1-hour (± 5 min) on Days 1-5, and 8-12, of a 28 day treatment cycle. Decitabine will be administered as per standard of care, at a dose of 20 mg/m2 on days 8-12 of a 28 day treatment cycle. Patients without evidence of clinical disease progression following their Day 25 (± 2 days) visit will receive a second planned treatment cycle. Patients demonstrating disease response or stability after each cycle may receive additional treatment cycles until disease progression. Twenty patients (10 patients with relapsed AML and 10 newly diagnosed AML patients who are not candidates for cytotoxic therapy) will be enrolled to further evaluate safety and clinical activity. |
Primary Objective: |
To determine if therapy with GO-203-2c in combination with decitabine results in at least 20% of patients achieving a clinical response (blast response, minor response, partial response, or complete response). |
Secondary Objectives: |
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Statistical Considerations
The primary endpoint of the Phase 1b study was to define the MTD of GO-203 and GO-203 in combination with decitabine. In the Phase 2 trial, twenty patients (10 relapsed AML and 10 newly diagnosed AML patients who are not candidates for cytotoxic therapy) will be enrolled to further understand safety and clinical activity. We hypothesis that the clinical responses between 2 groups of patients will be different therefore CR/CRi will be summarized as numbers and percentages with 90% CI for 2 groups of patients separately. If we see 2 out 10 (20%) patients with CR/CRi the 90% CI ranges from 4% to 51%. Number of cycles for the combination therapy will also be summarized as median and range for each group descriptively. PFS and OS will be determined by Kaplan-Meier analysis.
Background
In the United States, the estimated incidence of newly diagnosed AML cases during 2016 was 17,500. For patients who present with AML refractory to initial chemotherapy or in whom early relapse has occurred after first remission, particularly those in whom other high risk factors are present, there remains a long-standing unmet medical need to identify potential new therapies. Leukemia arises from a malignant stem cell population characterized by the capacity for self-renewal and resistance to cytotoxic agents. Leukemia stem cells (LSCs) play a critical role in mediating disease recurrence. Effective therapy for AML is dependent on developing strategies that effectively target the LSC population.
MUC1 expression has been detected on a majority of primary AML cells. Importantly, MUC1 expression is found at increased levels on AML progenitor cells manifesting the stem cell (CD34+/lineage-/CD38-) and early myeloid (CD34+/lineage-/CD38+) phenotypes, and at low to undetectable levels on normal hematopoietic stem cells. Moreover, AML cells, but not normal hematopoietic cells, are dependent on MUC1 for their growth and survival. These findings have indicated that MUC1 is a highly attractive target for the treatment of AML.
MUC1 expression has been detected on a majority of primary AML cells. Importantly, MUC1 expression is found at increased levels on AML progenitor cells manifesting the stem cell (CD34+/lineage-/CD38-) and early myeloid (CD34+/lineage-/CD38+) phenotypes, and at low to undetectable levels on normal hematopoietic stem cells. Moreover, AML cells, but not normal hematopoietic cells, are dependent on MUC1 for their growth and survival. These findings have indicated that MUC1 is a highly attractive target for the treatment of AML.
