Cancer and Blood Disorders Research

Physicians and researchers at the Aflac Cancer Center are conducting a series of clinical studies and trials to improve care for our young patients, in addition to adults, which include:

A Phase 3, double-blind, randomized, placebo-controlled, multicenter study of GBT440 Administered Orally to Patients with Sickle Cell Disease

• The purpose of this study is to compare a new oral drug, GBT440, with a placebo in a large number of subjects with sickle cell disease. The key purpose of this study is to establish the benefit and safety of GBT440.

A Pilot Study of Hydroxyurea Management in Kids: Intensive Versus Stable Dosage Strategies (HUGKISS)

• The HUGKISS trial addresses if an accelerated dosing of hydroxyurea safely results in improved blood and urine laboratory results, as well as reduced sickle cell related complications, compared to a fixed dose of hydroxyurea.

Effects of Sickle Hemoglobin on Brain Perfusion (Sickle-HOPE)

• The goal of this study is to develop and evaluate feasibility of a novel functional imaging protocol that maps cerebral blood flow and oxygen delivery for children at risk for stroke due to sickle hemoglobin.

A Phase IIA, Open-label, PK, Safety, Tolerability and Treatment Effect of GBT440 in Children with SCD (GBT440-007)

• The purpose of this study is to compare a new oral drug, GBT440, with a placebo in a large number of subjects with sickle cell disease. GBT440 may help slow down the destruction of red blood cells and improve the health of blood vessels in the brain.

Our clinical and translational researchers are investigating:

• Alternative donor transplant for sickle cell disease, using novel cell and immunotherapy to improve outcomes
• Transplant for adults with sickle cell disease (STRIDE-II)
• Examining late effects of transplant for sickle cell disease
• An online decision aid about treatments for sickle cell disease
• Novel cell and immunotherapy to reduce the risk of or to treat graft-versus-host-disease (GVHD)

Additionally, we are:

• One of a select group of centers offering gene therapy for sickle cell disease
• One of small number of centers offering CAR-T cell treatment for relapsed and refractory B ALL patients (Novartis)
• Members of the Primary Immune Deficiency Treatment Consortium (PIDTC), Pediatric Blood and Marrow Transplant Consortium (PBMTC), Blood and Marrow Transplant Clinical Trials Network (BMT CTN) and Sickle Transplant Alliance for Research (STAR)
• Offering haploidentical transplant with gene modified T-cells post-transplant to aid immune recovery (Bellicum)

The focus of our basic research is to:

• Identify the molecular pathways linked to the development and evolution of acute and chronic GVHD.
• Develop novel, nongenotoxic targeted conditioning for hematopoietic cell transplantation (HCT).
• Develop immunobiology of immune dysregulation.
• Develop gene therapy for hemophagocytic lymphohistiocytosis (HLH). 

Our researchers are investigating the metastasis (spread of cancer to another part of the body) of medulloblastoma, a type of brain tumor that occurs in infants and young children. In addition, they’re exploring safer, more effective methods of treatment for children with brain tumors.

Our clinical and translational research includes:

• Targeted therapeutics: The discovery of new medicines (targets) to change the way cancer cells behave. Our doctors are conducting clinical trials to test identified targeted therapeutics for children with brain tumors. 
• Genomic biomarkers: Insights into the biology of children’s brain tumors that have led to clinical trials to test new medicines. 
• Nanotechnology: The study and creation of targeted, molecular-sized nanoparticles to treat diseases. Nanomedicine has the potential to revolutionize the treatment and care of—and ultimately cure—childhood diseases and conditions.

Basic research includes:

• Regulation of medulloblastoma metastasis: Research to develop a drug therapy that stops the spread of medulloblastoma as an alternative to the often-damaging whole-brain radiation therapy, which follows surgery to remove a brain tumor. Currently, Tobey MacDonald, M.D., is studying medulloblastoma. However, if the approach is successful, it could potentially be applied to any kind of tumor anywhere in the body.
• Learn more about Dr. MacDonald’s research
• Oncogenic signaling in medulloblastoma: A study to find a gentler cure for medulloblastoma. Robert Castellino, M.D., is researching a gene called wild-type p53-induced phosphatase (WIP1).

Our grant-funded clinical research studies aim to better understand, detect and manage late effects of cancer therapy. Additionally, we aim to improve our ability to educate, empower and promote health in survivors.

Health-related outcomes

Our researchers are exploring:

• Patient-reported outcomes and quality of life
• Type and severity of late effects most commonly seen in survivors
• Cardiac late effects and models of coordinated care with cardiologists
• Ovarian and testicular late effects and how they relate to delayed puberty and infertility
• Skin cancer and the genetics of skin cancer
• Impact of treatment on body mass index (BMI), both underweight and overweight
• Physical activity and its impact on adolescent survivors’ health and quality of life using technology (smartphones, Fitbit Flex) and community-based exercise programs (local YMCAs)
• Survivor and family related barriers to participation in survivor healthcare
• Risky health behaviors in adolescent and young adult survivors and how to encourage a healthy lifestyle
• How to prevent late effects through early interventions (medications or physical therapy)
• Research methodology and statistical applications around clinical outcomes research

Our researchers also have leadership roles in the Children’s Oncology Group Long-Term Follow-Up Guidelines Task Force and the International Late Effects of Childhood Cancer Guideline Harmonization Group. These groups are national and international experts in survivorship that develop the guidelines used to help detect and prevent late effects in survivors.

Communication

We’re seeking new ways to inform and educate survivors about their health risks and improve their health and quality of life by:

• Tailoring evidence based communication strategies to increase survivors’ knowledge of survivor care and adherence to long-term follow up healthcare
• Developing methods of communicating infertility risk to adolescent and young adult survivors
• Educating Georgia primary healthcare providers about survivor care
• Using social media to improve adolescent and young adult transition

Cancer SurvivorLink

Cancer SurvivorLink is an online resource designed to support care for survivors of childhood cancer. It provides educational materials to improve awareness of survivorship issues, best practices in survivor care, and a secure way to electronically store and share health documents.

Our researchers are studying how SurvivorLink can improve access to survivorship care and patient knowledge about important survivor issues. We are:

• Evaluating the abilities of young adult (18-21 years old) patients to use SurvivorLink to manage their health records
• Assessing the impact of SurvivorLink on adherence to cancer survivor care and late effects visits and screening.
• Using iterative feedback to continuously enhance and improve SurvivorLink

Learn more about how to sign up and use SurvivorLink

Survivor health self-management and transition to adult care

The Children’s Oncology Group (COG) recommends that survivors receive ongoing survivor-specific care throughout their lives. When pediatric survivors grow up and become young adults, they need to be ready to manage their survivor care and transfer care from Children’s and the Aflac Cancer & Blood Disorders Center to adult doctors. Our team is conducting research to understand how we can best help survivors get ready for these responsibilities. Our projects focused on survivor health self-management and transition include:

• Adapting and validating the Readiness to Transition Questionnaire (RTQ), a survey measure of transition readiness that assesses shifts in healthcare responsibility from parents to adolescents
• Characterizing barriers to transition of survivor care and the subpopulations of survivors at risk for non-adherence post-transfer
• Evaluating the impact of transition clinics and meeting adult providers on successful transition to adult care
• Establishing a network of college health providers, who are knowledgeable of the needs of survivors, at colleges and universities throughout Georgia.

Partnership

• Childhood Cancer Survivor Study (CCSS): This National Cancer Institute funded study explores health problems that develop later in life as a result of cancer treatment, also known as late effects.
• Consortium for Pediatric Intervention Research: Consortium to support the feasibility of delivering intervention and develop opportunities for definitive clinical trials.

Gene therapy is an experimental technique that uses genes to treat or prevent disease. Using this therapy, researchers insert one or more corrective genes, which have been designed in the lab, into the genetic material of a patient's cells to correct the effects of a disease-causing mutation.

Our basic research in gene therapy focuses on hemophilia (a blood clotting disorder) and cancer.

Hemophilia A

Our researchers are focusing on factor VIII (fVIII), a protein involved in blood clotting:

• Recombinant viral vectors, which are used to deliver genetic materials into cells, have the potential to be a cure for hemophilia A.
• Using high-expression elements can reduce the cost of recombinant fVIII production—approximately 70 percent of patients with hemophilia A aren’t treated, and a reduction in the cost producing fVIII will increase access to the protein.

Learn more about gene therapy for hemophilia

Cancer

Our researchers are pioneering an approach to treat cancer using novel immunotherapies—treatments that use substances to stimulate the immune response—called drug resistance immunotherapy (DRI). They’re exploring whether immunocompetent cells (those with a normal immune response) can be genetically engineered to withstand the toxic effects of chemotherapy, and, if so, whether the genetic modification makes it possible to use both chemotherapy and cell-based immunotherapy. The ability to use both types of treatment, rather than a single approach, could improve survival rates.

The focus of our clinical research on hemostasis (stoppage of bleeding or hemorrhage) and thrombosis (blood clotting) includes rare bleeding diseases and platelet disorders.

Hemophilia
Hemophilia is a rare bleeding disorder in which the blood doesn't clot normally and causes internal bleeding into muscles and joints. Our researchers are exploring:

• Treatment of severe hemophilia A with secondary prophylaxis, which involves the infusion of a clotting factor to prevent bleeding
• Risk factors due to low bone density in hemophilia patients 
• Factor VIII (fVIII) inhibitors—which prevent blood from clotting normally—in patients with hemophilia undergoing surgery
• Mechanisms of fVIII inhibitor development 
• Treatment of hemophilia with therapies created by separating, purifying and concentrating proteins found in blood plasma, also known as recombinant products
• Pharmacokinetics (the movement of medicine within the body) and the safety of human recombinant fIX (medicine that controls bleeding) 
• 32P synovectomy, a treatment that uses radioactive compounds to treat hemophilia 
• Platelet function in hemophilia

In addition, researchers are studying:

• Rare bleeding disorders and the efficacy and safety of recombinant fXIII, a medicine that prevents bleeding
• Platelet dysfunction of immune and nonimmune (drug induced) thrombocytopenia, a deficiency of platelets in the blood that causes abnormal bleeding
• Risk factors for the development of thrombosis (blood clots) and treatments using recombinant products

Our basic and translational research focus includes:

• Mechanisms of fVIII inhibitor formation and its ability to cause disease
• Regulation of fVIII expression
• Development of fVIII products, which prevent bleeding
• Mechanisms of platelet activation and thrombosis

Our researchers are investigating safer, less toxic and more effective methods of treatment for children with leukemia (cancer of the blood) and lymphoma (cancer of the lymphatic tissues).

Our clinical and translational researchers are focusing studies on aberrant signaling nodes (lymph nodes that aren’t behaving normally) and novel medicines and combinations. Their research includes:

• Nanoscale proteomics: Kevin Bunting, Ph.D., and Himalee Sabnis, M.D., M.Sc., along with senior research technician Heath Bradley, are using the NanoPro 1000 system (equipment that performs biological analysis) to obtain precise and quantitative data of the phosphorylation states of proteins separated by isoelectric focusing. They’re developing new procedures to investigate signaling pathways in patient samples.
• mTOR targeted therapies: Frank Keller, M.D., (acute lymphoblastic leukemia) and Drs. Bunting and Sabnis (acute myeloid leukemia) are trying to inhibit the mTOR (an enzyme that regulates cell metabolism and growth) pathway using innovative approaches in combination with rapamycin, an anti-rejection medicine.

Basic research includes:

• MDM2 signaling in cancer treatment: Muxiang Zhou, M.D., and Lubing Gu, M.D., are searching for small-molecule compounds that insulate the connections between the MDM2 and XIAP genes. This insulating effect disrupts the signals from MDM2 to boost the production of the cancer-resistant XIAP, allowing cancer cells to become more sensitive to chemotherapy.
• STAT5/mTOR signaling: Dr. Bunting specializes in studying a molecule called STAT5, a protein that binds to DNA and regulates gene expression. The protein shows great promise as a treatment that would greatly reduce unwanted side effects, such as those that occur with radiation therapy. STAT5 could also lead to a revolutionary treatment of childhood cancer and other diseases.
• STAT5: Dr. Bunting is studying the biology of STAT5 and its role in normal production of blood cells, as well as its abnormal function associated with a variety of blood diseases. A major focus of his research is to identify genes associated with normal and leukemic (affected by leukemia) blood cell production and develop a treatment approach that manipulates STAT5 function. In addition, Dr. Bunting is studying the Grb2 protein (associated with leukemia) and its interaction with STAT5 to develop new therapies. 

Sickle cell disease is an inherited blood disorder that causes red blood cells to change shape.

Our researchers are seeking ways to improve outcomes and quality of life for children with this disease through blood and marrow transplantation (BMT) and transfusion medicine (the transfer of blood and blood components).

Our clinical and translational researchers are seeking a cure and looking for ways to improve treatments and the quality of life for children with the disease. They’re studying:

• Health outcomes and new therapies, such as hydroxyurea (a medicine) and stem cell transplantation 
• Prevention of sickle cell disease complications, such as kidney damage, pain and stroke
• Red blood cell alloimmunization, an undesired immune response that occurs after BMT 
• Micronutrients (vitamins and minerals)

Our basic researchers are exploring:

• Whether angiogenic growth factors (promote blood vessel formation) play a protective or destructive role in the structure of the lining of blood vessels in the lungs and in leg ulcers in sickle cell disease
• Antioxidant enzymes that protect the vessels in the lungs from oxidant-induced changes in the structural resistance of vessels in sickle cell disease pulmonary hypertension
• Cellular interactions in sickle cell disease to determine their relative contributions to blocked blood vessels, blood cell rupture or destruction, and the formation of reactive oxygen species (a natural byproduct of normal oxygen metabolism)
• The development of sickle cell disease in respect to the generation, prevention and treatment of organ dysfunction—specifically the role of endothelial (inner lining of blood vessel) cells in the generation of kidney disease
• Genetic association studies to identify markers that influence the incidence of pulmonary hypertension and leg ulcers in sickle cell disease
• Nanotechnology—the study and creation of targeted, molecular-sized nanoparticles to treat diseases—which has the potential to revolutionize the treatment and care of childhood conditions and could ultimately lead to cures

A solid tumor is an abnormal clump of cells that doesn't contain any liquid or cysts. They can occur in bones, tissues and organs.

Our researchers are looking for new ways to improve the health and quality of life for children with solid tumors by exploring:

• New medicines to change the way cancer cells behave, also called targeted therapeutics 
• New combinations of medicines
• Mechanisms involved in chemoresistance, a trait found in some cancers that make them less likely to respond to chemotherapy
• High-risk neuroblastoma therapy and outcomes 

Our basic research focus includes:

• Improving the effectiveness of chemotherapy in neuroblastoma treatment by targeting molecular structures that protect neuroblastoma cells 
• Biologic validation of Phase I agents 

Transfusion medicine involves transfusion of blood or blood components. It’s used to treat diseases such as bone cancer, leukemia, sickle cell disease and others.

Our clinical researchers are exploring ways to improve transfusion treatments and minimize potential complications by investigating:

• Transfusion-transmitted cytomegalovirus (CMV), a common virus that causes infection and can be dangerous for people with weakened immune systems
• Potential adverse effects of stored red blood cells
• Alloimmunization (an undesired immune response that can occur after transfusion) in sickle cell patients
• Development of a pediatric transfusion medicine training curriculum
• Transfusion medicine and hemostasis (stopping bleeding or hemorrhage) network trials

Our basic research focus includes:

• Red blood cell alloimmunization
• Blood and marrow transplantation (BMT) rejection primed by red blood cell or platelet transfusions
• Red blood cell autoimmunity (an immune response against an organism’s own cells and tissues)
• Red blood cell antigen loss