A Reason to Smile
SWCRF funded research helps a woman with a rare blood cancer find hope in an experimental treatment.
Barb Plumb is thankful for cancer research. The 73-year-old resident of Duluth, Minnesota, loves spending time with her son Eric and daughter Molly, works three days a week at The Amazing Alonzo Paperback Exchange, a bookstore she founded in 1982 with her late husband, and likes to go to concerts. She also has myelofibrosis, a bone marrow disorder that disrupts the body's normal production of blood cells. The result is extensive scarring in a person’s bone marrow, which leads to anemia, weakness, fatigue and often an enlarged spleen, which causes abdominal and back pain. Myelofibrosis (MF) often leads to a more serious form of leukemia. Barb is hopeful that her participation in a Phase 1 trial for Alisertib will help her avoid this progression.
“I’d probably be very, very ill if I weren’t on this drug,” she says. “In fact, I know I would be.”
Alisertib targets Aurora A kinase, a protein that in MF is hyperactive and contributes to abnormal development of megakaryocytes, the cells that produce platelets. Barb was first diagnosed in 1999 with a related blood disease called Essential Thrombocythemia (ET), which commonly evolves to MF or even acute myeloid leukemia. She was treated with Hydroxyurea, a drug commonly used to lower platelet counts, for 11 years. When doctors observed that her red blood cell counts were dropping in 2010, she underwent a bone marrow biopsy that revealed she had MF. Barb was referred to Dr. Ayalew Tefferi at the Mayo Clinic in Rochester, MN, who was overseeing a trial for Momelotinib, a JAK inhibitor that disrupts signaling pathways from Janus kinase 2, a gene that is mutated in the majority of patients with ET and MF. After five and a half years on Momelotinib, Barb began having night sweats and was referred to Dr. Tefferi’s colleague Dr. Naseema Gangat who was leading a trial that had recently opened for Alisertib.
|John Crispino, PhD|
The trial is based on investigative work, funded in part by the Samuel Waxman Cancer Research Foundation (SWCRF), by John Crispino, PhD, the Robert I. Lurie, MD and Lora S. Lurie Professor of Medicine, and Professor in the Department of Biochemistry and Molecular Genetics at Northwestern University. Dr. Crispino’s laboratory investigates the mechanisms of normal and malignant blood cell development, with an emphasis on understanding the growth of red blood cells and platelet-producing cells. His team also studies how changes in normal molecules lead to blood diseases.
The Alisertib trial launched in October of 2015 with a goal of recruiting 24 patients over a two-year period at Northwestern (Brady Stein, MD), the Mayo Clinic (Ayalew Tefferi, MD and Naseema Gangat, MD) and the University of Miami Cancer Center (Ronan Swords, MD). Barb, who has been a participant for about a year, is a trailblazer in the study as the first patient at the Mayo Clinic to take the drug.
Early results in her response to the treatment have been mixed but Barb emphasizes the good news over the bad. Within two weeks of starting the trial she lost all her hair, her hemoglobin and magnesium levels dropped and she experienced drowsiness and stomach discomfort. Barb notes, however, that her blood counts normalized in the first three weeks of the trial and the Alisertib seems to be staving off several conditions typically experienced by MF patients, including an enlarged spleen, bone pain and itching.
Barb remains upbeat about the treatment and her faith in research.
“I didn’t really think about research much before I was diagnosed with MF,” she says. “When I went from ET to MF, it was all new to me and they didn’t have anything for me here in Duluth. This is what has kept me alive and I swear that I wouldn’t be here if it weren’t for the two trials I’ve been on. I wouldn’t feel this good nor would I be able to work. I one-hundred-percent believe in research and trial drugs.”
Dr. Crispino is equally encouraged by Barb’s response to the drug and by the trial’s preliminary results overall. In addition to Barb, there are several other patients who have shown clear responses to Alisertib.
“The fact that she has been on this drug for over a year and is doing well is remarkable,” he says. “People with high-risk myelofibrosis generally live for 16 to 18 months.”
Findings from the study, which is still in its early stage, will be presented at the annual meeting of the American Society of Hematology in December. The study’s likely next phase will be to combine Alisertib with Ruxolitinib, a JAK inhibitor currently approved by the FDA to treat MF, in patients who have not previously been unsuccessfully treated with a JAK inhibitor.
Dr. Crispino credits grants provided by the SWCRF through donor support as a pivotal factor in making the Alisertib trial a reality.
“In this particular study, this work was funded at a very early stage of the research, and early-stage funding is very difficult to get from the NIH (National Institutes of Health), so foundations such as the SWCRF are instrumental and influential in enabling these high-risk studies,” he points out.
Seed funding from the SWCRF enabled Dr. Crispino and collaborators to conduct pre-clinical studies that subsequently secured additional financing for the Alisertib trial. Dr. Crispino also notes that his progress was greatly supported by scientific exchange with his longtime SWCRF Institute Without Walls collaborators Shai Izraeli, MD, of the Sheba Medical Center in Israel, Jonathan Licht, MD, of the University of Florida Cancer Center and Ross Levine, MD, of Memorial Sloan Kettering Cancer Center.
“The intellectual contributions of the collaborators through the SWCRF provided invaluable guidance to move this project forward.”