Clinical Trial Clinical Trial: A type of research study that tests how a drug, medical device, or treatment approach works in people. There are several types of clinical trials. Treatment trials test new treatment options. Diagnostic trials test new ways to diagnose a disease. Screening trials test the best way to detect a disease or health problem. Quality of life (supportive care) trials study ways to improve the comfort of people with chronic illness. Prevention trials look for better ways to prevent disease in people who have never had the disease. Trials are in four phases. Phase I tests a new drug or treatment in a small group to see if it is safe. Phase II expands the study to a larger group of people to find out if it works. Phase III expands the study to an even larger group of people to compare it to the standard treatment for the disease; and Phase IV takes place after the drug or treatment has been licensed and marketed to find out the long-term impact of the new treatment. If you are interested in learning more about your possible participation in this clinical trial, please complete the form. Your information will be forwarded directly to the trial sponsor.
The current standard treatment for aplastic anemia aplastic anemia: (ay-PLASS-tik uh-NEE_mee-uh) A rare and serious condition in which the bone marrow fails to make enough blood cells - red blood cells, white blood cells, and platelets. The term aplastic is a Greek word meaning not to form. Anemia is a condition that happens when red blood cell count is low. Most… (AA) is immunosuppressive therapy immunosuppressive therapy: Immunosuppressive drug therapy lowers your body's immune response. This prevents your immune system from attacking your bone marrow, allowing bone marrow stem cells to grow, which raises blood counts. For older patients with acquired aplastic anemia, immunosuppressive drug therapy is the… (IST), with only temporary symptom relief and high rates of paroxysmal nocturnal hemoglobinuria paroxysmal nocturnal hemoglobinuria: (par-uk-SIZ-muhl nok-TURN-uhl hee-muh-gloe-buh-NYOOR-ee-uh) A rare and serious blood disease that causes red blood cells to break apart. Paroxysmal means sudden and irregular. Nocturnal means at night. Hemoglobinuria means hemoglobin in the urine. Hemoglobin is the red part of red blood cells. A… , clonal hematopoiesis hematopoiesis: (hi-mat-uh-poy-EE-suss) The process of making blood cells in the bone marrow. , and myelodysplastic syndrome. When a matched donor is available, allogeneic hematopoietic cell transplant (allo-HCT) is the preferred treatment for severe aplastic anemia (SAA). But the survival rate for patients over 40 years of age is ~ 50%, mainly due to graft-versus-host disease (GvHD) graft-versus-host disease (GvHD): Also called GVHD, it is a common complication of bone marrow/stem cell transplantation. It is caused when the donor's immune cells, now in the patient, begin to see the the patient's body as foreign and mount an immune response. GVHD most commonly effects the recipient's skin, intestines, or liver… . There is an urgent need to find novel therapies for SAA patients who are refractory refractory: Not responsive to treatment or cure. For example, refractory anemia is a low red blood cell count that doesn't respond to standard treatments. to IST and lack a matched donor.
Mixed chimerism (MC) is the co-existence of both host- and donor-derived cells in the recipient. Previous studies in SAA have shown that patients who develop stable MC after allo-HCT have improved clinical outcome. The Zeng lab at City of Hope has developed a novel regimen for induction of MC after HCT in mouse models. The regimen includes a non-myeloablative conditioning regimen (low dose of cyclophosphamide cyclophosphamide: Cyclophosphamide is in a class of medications called alkylating agents. When used to treat cancer, it works by slowing or stopping the growth of cancer cells in your body. When cyclophosphamide is used to treat bone marrow failure, it works by suppressing your body's immune system. , pentostatin, anti-thymocyte globulin), and CD4+ T-depleted hematopoietic cell graft. Reasons for using CD4+ T-cell-depleted grafts are CD4+ T cells mediate GvHD that damages bone marrow bone marrow: The soft, spongy tissue inside most bones. Blood cells are formed in the bone marrow. and hampers donor stem cell engraftment engraftment: Refers to how well a graft (donor cells) is accepted by the host (the patient) after a bone marrow or stem cell transplant. Several factors contribute to better engraftment - physical condition of the patient, how severe the disease is, type of donor available, age of patient. Successful… and depletion of CD4+ T cells prevents GvHD in recipients with complete chimerism. Zeng lab studies demonstrate that induction of full MHC-mismatched or haplo-MHC-matched MC by this regimen in mouse models cures autoimmune diseases, without causing GvHD.
In a recent COH clinical trial clinical trial: A type of research study that tests how a drug, medical device, or treatment approach works in people. There are several types of clinical trials. Treatment trials test new treatment options. Diagnostic trials test new ways to diagnose a disease. Screening trials test the best way to detect a… using the same regimen in three patients with sickle cell disease, the therapy was shown to be safe, COH-MC-17 regimen safely induced haploidentical MC in two patients. In this clinical trial, we plan to extend this regimen to induce haploidentical MC in SAA. The goals of this study are to evaluate the safety and feasibility of COH-MC-17 regimen; and demonstrate the capacity to induce MC in SAA patients.
Patients with confirmed diagnosis of severe
aplastic anemia
aplastic anemia:
(ay-PLASS-tik uh-NEE_mee-uh) A rare and serious condition in which the bone marrow fails to make enough blood cells - red blood cells, white blood cells, and platelets. The term aplastic is a Greek word meaning not to form. Anemia is a condition that happens when red blood cell count is low. Most…
, aged 40-75 years old, who have failed at least one trial of
immunosuppressive therapy
immunosuppressive therapy:
Immunosuppressive drug therapy lowers your body's immune response. This prevents your immune system from attacking your bone marrow, allowing bone marrow stem cells to grow, which raises blood counts.
For older patients with acquired aplastic anemia, immunosuppressive drug therapy is the…
(IST) by being
refractory
refractory:
Not responsive to treatment or cure. For example, refractory anemia is a low red blood cell count that doesn't respond to standard treatments.
or having relapsed. Patients must have a haploidentical donor available (with no matched donor) AND the treating clinician considers haploidentical transplant the preferred choice due to patient's clinical status.
Inherited
bone marrow failure
bone marrow failure:
A condition that occurs when the bone marrow stops making enough healthy blood cells. The most common of these rare diseases are aplastic anemia, myelodysplastic syndromes (MDS) and paroxysmal nocturnal hemoglobinuria (PNH). Bone marrow failure can be acquired (begin any time in life) or can be…
syndromes such as
Fanconi anemia
Fanconi anemia:
A rare inherited disorder that happens when the bone marrow does not make enough blood cells (red cells, white cells, and platelets). Fanconi anemia is diagnosed early in life. People with Fanconi anemia have a high likelihood of developing cancer. Genetic testing is used to diagnose Fanconi anemia.
must be ruled out according to center standards.
Clonal cytogenetic abnormalities consistent with pre-myelodysplastic syndrome (pre-MDS) or MDS on marrow examination (e.g.
Monosomy 7
Monosomy 7:
Describes the loss of one of the two number 7 chromosomes. "Mono" means one and "somy" comes from the word chromosome. A laboratory test called fluorescence in situ hybridization (FISH) detects monosomy 7 and other genetic abnormalities. Monosomy 7 can occur in adult patients…
).
High risk somatic mutations other than PIG-A (PNH) or BCOR
mutation
mutation:
Any change or alteration in a gene. A mutation may cause disease or may be a normal variation. Paroxysmal nocturnal hemoglobinuria (PNH) occurs because of a mutation in the PIG-A gene of a single stem cell in the bone marrow.
Diagnosis of myelodysplastic syndrome (MDS).
Presence of donor specific antibodies (see main text for details)
Prior allogeneic stem cell/bone marrow transplant
Concurrent other investigational agents,
chemotherapy
chemotherapy:
(kee-moe-THER-uh-pee) The use of medicines that kill cells (cytotoxic agents). People with high-risk or intermediate-2 risk myelodysplastic syndrome (MDS) may be given chemotherapy to kill bone marrow cells that have an abnormal size, shape, or look. Chemotherapy hurts healthy cells along with…
, biological therapy or radiation therapy
Major surgery within the last 30 days
Clinically significant liver
fibrosis
fibrosis:
(fie-BRO-suss) Scarring of tissue. Fibrosis of the bone marrow is an feature seen in some types of unclassified myeldysplastic syndrome (MDS).
or cirrhosis if on chronic transfusion therapy > 6 months
Active infection.