Recently, the Food and Drug Administration (FDA) has lifted its partial hold on the Xencor leukemia trial after the incident involving two deaths a few months back. In agreement with the FDA, Xencor stated that it has made changes to the study protocol, increasing monitoring and clinical management standards to avoid future similar cases.
In February this year, California-based company Xencor has announced that its Phase I clinical trial of the drug XmAb14045 used to treat Acute Myeloid Leukemia (AML), has been placed on partial hold by the FDA following two deaths that seem to be possibly related to the study. As such, participants already on the study may continue but no new patients will be enrolled.
The clinical trial was planned to test the “safety and tolerability” of the drug given to over 100 participants through weekly infusions, allowing the company to set the maximum tolerated dosage and schedule. These participants include those who have leukemia but failed prior therapies and currently are unable to undergo other standard therapies.9
The partial hold has since been lifted1 and the Xencor leukemia study will continue. This is good news to many, as countless research studies on leukemia have been conducted over decades, although currently there are no drug or treatment that can guarantee a cure for patients.
One of the most common cancers
Sometimes referred to as blood cancer, leukemia is the most common cancer in children ages two to five. Acute Lymphocytic Leukemia (ALL) accounts for 75 per cent of childhood leukemia, while most of the remaining cases are Acute Myeloid Leukemia (AML) – both forms of acute leukemias.2
Based on two-year data from 2014 to 2016, approximately 1.6 per cent of adults will be diagnosed with leukemia at some point of their life and is regarded a fairly common cancer among adults. According to the statistics compiled by the US National Cancer Institute, there will be 61,780 estimated new cases and 22,840 deaths in just 2019 alone.3
Each day, the bone marrow produces billions of new blood cells consisting of white blood cells, red blood cells and platelets. The cancer starts in the blood-forming cells in the bone marrow and changes from a normal cell into a leukemia cell. These cells remain in the marrow, building up the number of leukemia cells. As a result, when the amount of leukemia cells increases, the bone marrow can no longer contain them. Once this happens, the cells spill out into the bloodstream, causing a spike in the number of white blood cells in the blood. The blood containing leukemia cells then spread throughout the entire body and organs and prevents the other normal healthy cells from functioning as they should, causing a rapid deterioration of bodily functions. This is where leukemia is dissimilar to other cancers which start in the affected organ – such as the lungs, breast, colon – and then spread to bone marrow.4
Acute vs Chronic
Although there are various types of leukemia, it is comprised of two major groups – acute or chronic, lymphoid or myeloid – where acute leukemias are stated to be more commonly seen.
Depending on the type of white blood cells affected and factors such as the speed of degeneration, individuals can develop a different type of leukemia.
Acute leukemias affects the stem cells which causes both normal and leukemia cells to divide at an abnormally fast rate and does not stop reproducing when they should have. This then results in the leukemia cells spreading into the bloodstream more quickly than usual, bringing the cancerous cells to other organs and the central nervous system. This is also where acute leukemia got its name, as the process is fast-paced. Without suitable treatment methods, the patient could suffer life-threatening consequences, although it is somewhat easier to cure than chronic leukemia which often show less symptoms and are harder to spot.5
On the other hand, chronic leukemia comes about at a much slower rate. While acute leukemia affects the immature cells, chronic leukemia starts from the mature cells which progressively develop into leukemia cells. Most patients with the disease do not show symptoms and go about their daily lives not knowing about the cancer forming in their body. This is where chronic leukemia is dangerous, as the affected mature cells usually do not respond as well to treatment and drugs thus making the disease harder to fight off.
You have probably heard of the most common treatments for cancer – chemotherapy. However, there are several undesirable side effects because of the way it works and the cells it damages in the process.
Chemotherapy puts an end to fast multiplying cells such as cancerous ones, however there are other normal cells that are meant to be quickly multiplying such as hair follicles and stomach tracts. Therefore, the common side effects will include hair loss, anemia, diarrhea, fatigue among others.6
Other known treatments include stem cell transplant, radiation therapy, drugs and clinical trials such as the one conducted by Xencor.
Xencor clinical trial
Xencor’s early phase clinical trial of the drug XmAb14045 is among the company’s range of monoclonal antibodies in clinical development, which has been manufactured using its XmAB technology.
The two reported deaths were from a cytokine release syndrome (a systemic inflammatory response triggered by certain immunotherapies) and an acute pulmonary edema after several doses, possibly related to taking the drug.9
At that point of time, Xencor’s CEO Bassil Dahiyat stated that “Patient safety is Xencor’s highest concern” and that they are in talks with the FA investigators. He also mentioned that the other on-going studies were not affected.7
Phase I of the drug trial is meant to treat patients with Acute Myeloid Leukemia, B-cell Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia and Blastic Plasmacytoid Dendritic Cell Neoplasm, as mentioned in the clinical trial document.8