Purpose of this Study
We are doing this study to find the most effective, safe dose of an experimental drug called ziftomenib (the study drug). We want to know how well this study drug works in people with AML that have certain mutations in the NPM1 gene and rearrangements involving the KMT2A gene when it is given alone or in combination with other cancer drugs.
Who Can Participate?
Eligibility
Adults ages 18+ who are diagnosed with AML that has documented NPM1 mutation or KMT2A rearrangement. If a study candidate has relapsed/refractory AML, they must have reappearance of at least 5% blasts in the bone marrow or reappearance of blasts in the blood in at least 2 peripheral blood samples.
For more information about who can join this study, please contact the study team at 919-660-7262.
For more information about who can join this study, please contact the study team at 919-660-7262.
What is Involved?
If you choose to join this study, you will go through a screening period to find out if you are eligible. During this screening period, you will:<ul>
<li>Have a physical exam</li>
<li>Have a heart scan (ECG)</li>
<li>Have blood draws</li>
<li>Have cancer cells tested for the presence of the NPM1 mutation and KMT2A rearrangement along with FLTe or other mutations</li></ul>
After the screening period, you will begin the study drug period. This part of the study is divided into 2 parts. Part 1a (dose escalation) is to determine the safest, most effective dose of the study drug in combination with other cancer drugs. Part 1b (dose validation expansion) will happen once the most appropriate combinations and dose levels have been determined from Part 1a.
Part 1a will be made up of the following cohorts:<ul>
<li><strong>A-2:</strong> The study drug will be given in combination with cytarabine plus daunorubicin in patients who have never been treated for AML and have an NPM1 mutation</li>
<li><strong>B-2:</strong> The study drug will be given in combination with cytarabine plus daunorubicin in patients who have never been treated for AML and have a KMT2A rearrangement</li>
<li><strong>A-1:</strong> The study drug will be given in combination with venetoclax and azacitidine in patients who have been treated for AML but did not respond to therapy and have an NPM1 mutation</li>
<li><strong>B-1:</strong> The study drug will be given in combination with venetoclax and azacitidine in patients who have been treated for AML but did not respond to therapy and have a KMT2A rearrangement</li></ul>
Part 1b will be made up of the following cohorts:<ul>
<li><strong>A-3:</strong> The study drug will be given in combination with venetoclax in patients who have been treated but have not responded to standard therapy and have an NPM1 mutation</li>
<li><strong>A-4:</strong> The study drug will be given in combination with venetoclax and azacitidine in patients who have never been treated for AML and have an NPM1 mutation</li>
<li><strong>B-3:</strong> The study drug will be given in combination with venetoclax and azacitidine in patients who have never been treated for AML and have a KMT2A rearrangement</li></ul>
Whether you are in Part 1a or Part 1b of the study will depend on when you join the study. The cohort to which you are assigned in either part will depend on your diagnosis and treatment history.
Each study drug cycle is 28 days. You will start taking the study drug on Day 8 of each cycle, unless you are enrolled in cohort A-3. If you are enrolled in Cohort A-3, you will start taking the study drug on Day 1. The study drug is taken by mouth. All other drugs are given by IV infusion or by subcutaneous injection.
The number of study drug cycles you do will depend on how you tolerate the regimen, how your cancer responds to the regimen, and your overall wellbeing.
<li>Have a physical exam</li>
<li>Have a heart scan (ECG)</li>
<li>Have blood draws</li>
<li>Have cancer cells tested for the presence of the NPM1 mutation and KMT2A rearrangement along with FLTe or other mutations</li></ul>
After the screening period, you will begin the study drug period. This part of the study is divided into 2 parts. Part 1a (dose escalation) is to determine the safest, most effective dose of the study drug in combination with other cancer drugs. Part 1b (dose validation expansion) will happen once the most appropriate combinations and dose levels have been determined from Part 1a.
Part 1a will be made up of the following cohorts:<ul>
<li><strong>A-2:</strong> The study drug will be given in combination with cytarabine plus daunorubicin in patients who have never been treated for AML and have an NPM1 mutation</li>
<li><strong>B-2:</strong> The study drug will be given in combination with cytarabine plus daunorubicin in patients who have never been treated for AML and have a KMT2A rearrangement</li>
<li><strong>A-1:</strong> The study drug will be given in combination with venetoclax and azacitidine in patients who have been treated for AML but did not respond to therapy and have an NPM1 mutation</li>
<li><strong>B-1:</strong> The study drug will be given in combination with venetoclax and azacitidine in patients who have been treated for AML but did not respond to therapy and have a KMT2A rearrangement</li></ul>
Part 1b will be made up of the following cohorts:<ul>
<li><strong>A-3:</strong> The study drug will be given in combination with venetoclax in patients who have been treated but have not responded to standard therapy and have an NPM1 mutation</li>
<li><strong>A-4:</strong> The study drug will be given in combination with venetoclax and azacitidine in patients who have never been treated for AML and have an NPM1 mutation</li>
<li><strong>B-3:</strong> The study drug will be given in combination with venetoclax and azacitidine in patients who have never been treated for AML and have a KMT2A rearrangement</li></ul>
Whether you are in Part 1a or Part 1b of the study will depend on when you join the study. The cohort to which you are assigned in either part will depend on your diagnosis and treatment history.
Each study drug cycle is 28 days. You will start taking the study drug on Day 8 of each cycle, unless you are enrolled in cohort A-3. If you are enrolled in Cohort A-3, you will start taking the study drug on Day 1. The study drug is taken by mouth. All other drugs are given by IV infusion or by subcutaneous injection.
The number of study drug cycles you do will depend on how you tolerate the regimen, how your cancer responds to the regimen, and your overall wellbeing.
Study Details
Full Title
Phase 1 study of venetoclax/azacitidine or venetoclax in combination with
ziftomenib (KO-539) or standard induction cytarabine/daunorubicin (7+3) chemotherapy in combination with ziftomenib for the treatment of patients with acute myeloid leukemia
ziftomenib (KO-539) or standard induction cytarabine/daunorubicin (7+3) chemotherapy in combination with ziftomenib for the treatment of patients with acute myeloid leukemia
Principal Investigator
Harry
Erba
Protocol Number
PRO00113005
NCT ID
NCT05735184
Phase
I
Enrollment Status
Open to Enrollment