University of Illinois Cancer Center researchers are leading a multicenter study to learn whether the combination of cancer drugs Gemtuzumab and Venetoclax can kill leukemia stem cells, thus eradicating leukemia in patients suffering from relapsed/refractory acute myeloid leukemia (AML).
“As Gemtuzumab kills leukemia cells through inducing a form of cell death called apoptosis, and Venetoclax primes cancer cells to undergo apoptosis, the synergy of the combination should prove effective in patients with leukemia,” said John Quigley, MD, associate professor of hematology/oncology at the University of Illinois College of Medicine who is leading a clinical trial to determine the drugs’ effectiveness.
The phase Ib trial is open to patients 18 to 75 years of age who, at the time of recruitment, have had AML relapse or have not responded to treatment, and in whom at least 20% of their leukemia blasts express the cell-surface marker CD33. Potential candidates must have good organ function and have received no more than three lines of prior therapy. Previous treatment with any medication other than the study drugs (Venetoclax and Gemtuzumab) is allowed, Quigley said.
Five patients (a total of 24 patients are being recruited) have been enrolled to date, and none have encountered treatment related dose-limiting toxicities, said Quigley, who is also a member of the University of Illinois Cancer Center’s Translational Oncology program. The study, therefore, is actively recruiting patients to complete the second of three cohorts. The aim is to complete patient enrollment before April 2021.
In addition to UI Health, the study, which is sponsored by the Big Ten Cancer Research Consortium, is open to patients at Indiana University Melvin and Bren Simon Comprehensive Cancer Center, the Fred & Pamela Buffet Cancer Center at the University of Nebraska, and the University of Michigan Rogel Cancer Center.
The study will use a 3+3 design to identify the maximum tolerated dose for patients. Starting with a low dose, three patients are followed for a predetermined amount of time to learn if they experience a toxicity to the medications that limit their ability to safely receive the regimen (termed “dose-limiting toxicity,” or DLT). Should no patient experience a DLT, three additional patients are recruited and administered an increased dose of the medication (in this instance Venetoclax). This process is repeated until the predefined maximum dose of Venetoclax is reached. The maximum tolerated dose is the level at which less than 33% of the subjects experience a dose-limiting toxicity, said Saad Arain, MD, a hematology/oncology fellow assisting Quigley with the clinical trial.
AML is a rare type of blood cancer that starts in the blood-forming cells of the bone marrow, and comprises approximately 1% of cancers in the United States. An estimated 19,940 people will be diagnosed with the disease in 2020. AML is uncommon in people under the age of 45, with the average age of diagnosis being 68 years old, according to the American Society of Clinical Oncology (ASCO). It is estimated that 11,180 deaths will occur this year due to AML – the majority in adults. The five-year survival rate – the percentage of people who live at least five years after the cancer is discovered – for people age 20 or under with AML is about 25%.
The study, according to Quigley, will not only investigate the maximum safe and tolerated dose of this novel combination therapy but will also include measures designed to evaluate the efficacy of the regimen.
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