April 29, 2019:

A Big Ten Cancer Research Consortium phase I/II study is testing the safety and efficacy of combining ixazomib and romidepsin in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). The study is now open for accrual at the University of Michigan Rogel Cancer Center, Rutgers Cancer Institute of New Jersey, the University of Illinois Cancer Center in Chicago, and Holden Comprehensive Cancer Center at the University of Iowa.

About 75,000 new cases of non-Hodgkin lymphoma were diagnosed in 2018.

PTCL is a rare subtype of non-Hodgkin lymphoma that develops from T-cells, white blood cells that are critical to the body’s immune system. Unspecified PTCL, the most common form of PTCL, has a poor response rate to treatment and represents about 10 to 15 percent of all non-Hodgkin lymphomas.

“Just over 50% of those patients express a particular protein that we show confers resistance to chemotherapy,” said Ryan Wilcox, MD, PhD, sponsor-investigator and medical oncologist at the University of Michigan Rogel Cancer Center. “We are investigating ways to try and target that protein either by reducing its expression or impairing its function.”

Because PTCL doesn’t fit specific distinct characteristics, Dr. Wilcox said, investigators try to determine what works and also apply treatment that is offered for other lymphomas. He would like to identify more specific treatments for subtypes of PTCL.

“Current therapies are extrapolated from how we would manage similar patients with aggressive B-cell lymphomas,” he said. “Ideally, we would like to be able to determine prior to treatment that this patient will respond to drug A, whereas that patient will respond to drug B.”

Patients with PTCL are usually treated with chemotherapy, radiation therapy, stem cell transplant, and steroid therapy. Other drugs to treat PTCL are available, but the response rate is still low, according to Dr. Wilcox.

The study, BTCRC-HEM15-028, “Phase I/II Study of Ixazomib and Romidepsin in Relapsed/Refractory Peripheral T-cell Lymphoma (PTCL),” will test the safety of combining ixazomib and romidepsin as well as measure the response rate of patients whose tumor shrinks or shows a complete response.

Ixazomib is a proteasome inhibitor, which blocks the machinery that breaks down damaged proteins, allowing buildup of these proteins in the cancer cell, leading to cell death. Ixazomib is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy.

Romidepsin is a histone deacetylase (HDAC) inhibitor, which blocks certain proteins that modify DNA-associated proteins. Blocking HDACs interferes with the genetic make-up of cancer cells and causes cell death. Currently, romidepsin is approved by the FDA to treat cutaneous T-cell lymphoma and peripheral T-cell lymphoma.

Combining ixazomib and romidepsin has not been approved by the FDA and should be considered investigational.

“The objective of the initial phase of this study is to determine the best dose or the maximum dose when these two agents are used in combination,” Dr. Wilcox said. “Once that is determined, subsequent patients enrolled on the trial will be treated at that maximum, or what we believe to be the best, dose.”

Dr. Wilcox said previous studies conducted with ixazomib demonstrate that ixazomib can impair the expression of the protein they are targeting. They also have shown favorable results in romidepsin, so investigators would like to see how these two drugs work together.

The study, which is supported by Takeda Pharmaceuticals, will include up to 48 people with relapsed or refractory peripheral T-cell lymphoma after standard upfront chemotherapy with documented disease progression.

Researchers will study combining ixazomib and romidepsin in two parts. During the first portion, scientists will identify the safe dose of romidepsin combined with ixazomib among up to 36 participants. During the second part, in which 12 subjects will participate, researchers will determine the percentage of patients whose tumor experienced a complete response after receiving ixazomib and romidepsin.

Participants will be treated in cycles lasting 28 days (4 weeks). In each cycle, patients will receive romidepsin through an IV once a week for either two or three weeks and then have a break until the next cycle begins. Participants will take ixazomib, a pill, once a week for three weeks, typically after the infusion, and then have a break until the new cycle begins.

Subjects may continue to receive study treatment until their cancer worsens or they experience intolerable side effects. Participants may discontinue treatment at any time in consultation with their oncologist.

Correlative research, in which proteins will be studied, will supplement this study. Blood will be collected as well as tissue obtained from a previous biopsy or surgery. Additional blood or tissue may be collected for exploratory research with consent from the participant.

To qualify for this study, patients must be adults age 18 or older with relapsed or refractory peripheral T-cell lymphoma who have received previous treatment.

For more information about this research study, including full eligibility requirements, visit www.clinicaltrials.gov (study #NCT03547700).

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 almost 9,500 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.