September 29, 2020:

A phase Ib Big Ten Cancer Research Consortium multi-center study is testing the safety and efficacy of the monoclonal antibody gemtuzumab ozogamicin when combined with the BCL-2 inhibitor venetoclax in adults with relapsed or refractory acute myeloid leukemia.

The study is open to accrual at the University of Illinois Cancer Center in Chicago, Ill.; the Indiana University Melvin and Bren Simon Comprehensive Cancer Center in Indianapolis, Ind.; the University of Michigan Rogel Cancer Center in Ann Arbor, Mich.; and the Fred & Pamela Buffett Cancer Center at the University of Nebraska.

Acute Myeloid Leukemia, also known as AML, is a disease that occurs when the bone marrow creates abnormal myeloblasts (a type of white blood cell), or, less frequently abnormal red blood cells or platelets. In the United States, approximately 21,450 new cases occurred in 2019. Typically, adults age 65 and older are at greater risk of being diagnosed with AML and prognosis for survival remains poor, especially with relapsed or refractory disease.

People with AML are usually treated with chemotherapy and sometimes with targeted therapies.

The primary goal of BTCRC-AML17-113, “Phase Ib study of the safety and efficacy of Gemtuzumab Ozogamicin (GO) and Venetoclax in patients with relapsed or refractory CD33+ acute myeloid leukemia,” is to find the maximum tolerated dose of venetoclax when combined with gemtuzumab ozogamicin.

Researchers hope to determine whether combining gemtuzumab ozogamicin with venetoclax is better, the same, or worse than the usual approach to treating adult patients with relapsed or refractory AML.

“Both of these drugs act to kill leukemia cells through induction of mitochondrial apoptosis; we believe that the combination therapy will be effective in these poor-prognosis AML patients,” said John Quigley, MD, sponsor-investigator of the study and a hematologist at the University of Illinois Cancer Center.

The research team has several secondary objectives, including determining the overall response rate, progression-free survival, event-free survival, and overall survival. Researchers also want to identify what adverse effects the therapy may cause and how the therapy impacts quality of life.

About the Drugs

Venetoclax works by targeting BCL-2 proteins, which play a role in regulating apoptosis (a form of cell death) in leukemia cells.

Currently, venetoclax is approved by the U.S. Food and Drug Administration (FDA) in combination with azacitidine, decitabine, or low-dose cytarabine to treat newly diagnosed AML patients who are age 75 or older or who have medical conditions that prevent the use of intensive chemotherapy. Venetoclax is also approved to treat adults with chronic lymphocytic leukemia or small lymphocytic lymphoma (SLL).

Gemtuzumab ozogamicin is an antibody-drug conjugate that targets the potent cytotoxin calicheamicin to CD33 proteins on the surface of leukemia cells. The drug is then transported inside the cell, where it causes damage leading to apoptosis and cell death. Gemtuzumab ozogamicin is approved by the FDA to treat adults with newly diagnosed AML who tested positive for CD33, and adults and children ages 2 and older with relapsed or refractory AML who tested positive for CD33.

The combination of gemtuzumab ozogamicin and venetoclax is not approved to treat relapsed or refractory AML and should be considered investigational.

About the Study Design

The study will be conducted in three parts: induction, consolidation, and maintenance. During the induction phase, study participants will receive 3 days of gemtuzumab ozogamicin (on Days 1, 4, and 7), along with daily oral venetoclax. Those who experience a complete response or partial response to treatment will go on to the consolidation phase, where they will receive 2 days of gemtuzumab ozogamicin (on Days 1 and 4), plus daily oral venetoclax. Participants who continue to experience a response to treatment will then go on to the maintenance phase of the study, where they will receive daily oral venetoclax alone.

Participants should expect to be hospitalized for the first few weeks of the study to ensure their blood counts recover after treatment.

The study will enroll up to 24 adults with relapsed or refractory AML.

For more information about this research study, including full eligibility requirements, visit www.clinicaltrials.gov (study #NCT04070768).

Support for this study is provided by Pfizer Inc. and AbbVie Inc.

About the Big Ten Cancer Research Consortium: The Big Ten Cancer Research Consortium was created in 2013 to transform the conduct of cancer research through collaborative, hypothesis-driven, highly translational oncology trials that leverage the scientific and clinical expertise of Big Ten universities. The goal of the Big Ten Cancer Research Consortium is to create a unique team-research culture to drive science rapidly from ideas to new approaches to cancer treatment. Within this innovative environment, today’s research leaders collaborate with and mentor the research leaders of tomorrow with the unified goal of improving the lives of all patients with cancer.

About the Big Ten Conference: The Big Ten Conference is an association of world-class universities whose member institutions share a common mission of research, graduate, professional and undergraduate teaching and public service. Founded in 1896, the Big Ten has sustained a comprehensive set of shared practices and policies that enforce the priority of academics in the lives of students competing in intercollegiate athletics and emphasize the values of integrity, fairness and competitiveness. The broad-based programs of the 14 Big Ten institutions will provide over $200 million in direct financial support to more than 9,800 students for more than 11,000 participation opportunities on 350 teams in 42 different sports. The Big Ten sponsors 28 official conference sports, 14 for men and 14 for women, including the addition of men’s ice hockey and men’s and women’s lacrosse since 2013. For more information, visit www.bigten.org.