A Phase IIb clinical trial of lintuzumab (SGN-33) in older patients with AML (acute myeloid leukemia) was discontinued because it did not extend overall survival, Seattle Genetic, Inc., announced today. The company said it will discontinue its development program for lintuzumab. Lintuzumab is a naked monoclonal antibody which targets the CD33 antigen.
The trial was a Phase IIb randomized, double-blind, placebo-controlled, multi-center clinical trial involving 211 patients, all aged at least 60 years with untreated acute myeloid leukemia who were unable to receive intensive chemotherapy.
The main aim of the trial (its primary endpoint) was to determine whether patients survived for longer with the combination of lintuzumab and low-dose cytarabine chemotherapy compared to low-dose cytarabine plus placebo.
Seattle Genetics announced that there was not a statistically significant difference between the lintuzumab group and the placebo control group in overall survival. Lintuzumab was well tolerated in combination with cytarabine chemotherapy.
Thomas C. Reynolds, M.D., Ph.D., Chief Medical Officer of Seattle Genetics, said:
We are disappointed that lintuzumab did not demonstrate a survival benefit for older AML patients in this study. These patients have limited therapeutic alternatives due to their inability to tolerate the toxicities associated with standard high-dose chemotherapy, representing a substantial unmet medical need. We want to thank the patients, caregivers and investigators for their participation and commitment to the clinical evaluation of lintuzumab.
Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics, said:
There is a lot of positive momentum at Seattle Genetics and we continue to focus on advancing our lead product candidate, brentuximab vedotin (SGN-35), and our robust pipeline. We are on track to report top-line data from two brentuximab vedotin clinical trials within the next six weeks, positioning us for a regulatory submission in the first half of 2011. In addition, our strong financial position allows us to continue to invest in advancing our multiple other programs, including two antibody-drug conjugates, SGN-75 and ASG-5ME, which are both in ongoing phase I clinical trials.
A patient with leukemia suffers from chaotic production of blood cells, generally leukocytes (white blood cells).
The DNA of immature blood cells, mainly white cells, becomes damaged in some way. This abnormality causes the blood cells to grow and divide chaotically. Normal blood cells die after a while and are replaced by new cells which are produced in the bone marrow. The abnormal blood cells do not die so easily, and accumulate, occupying more and more space. As more and more space is occupied by these faulty blood cells there is less and less space for the normal cells – and the sufferer becomes ill. Quite simply, the bad cells crowd out the good cells in the blood.
Types of leukemia
Chronic and Acute – Experts divide leukemia into four large groups, each of which can be Acute, which is a rapidly progressing disease that results in the accumulation of immature, useless cells in the marrow and blood, or Chronic, which progresses more slowly and allows more mature, useful cells to be made. In other words, acute leukemia crowds out the good cells more quickly than chronic leukemia.
Lymphocytic and Myelogenous – Leukemias are also subdivided into the type of affected blood cell. If the cancerous transformation occurs in the type of marrow that makes lymphocytes, the disease is called lymphocytic leukemia. A lymphocyte is a kind of white blood cell inside your vertebrae immune system. If the cancerous change occurs in the type of marrow cells that go on to produce red blood cells, other types of white cells, and platelets, the disease is called myelogenous leukemia.
To recap, there are two groups of two groups – four main types of leukemia, as you can see in the illustration below:
Acute Lymphocytic Leukemia (ALL) – This is the most common type of leukemia among young children, although adults can get it as well, especially those over the age of 65. Survival rates of at least five years range from 85% among children and 50% among adults. The following are all subtypes of this leukemia: precursor B acute lymphoblastic leukemia, precursor T acute lymphoblastic leukemia, Burkitt’s leukemia, and acute biphenotypic leukemia.
Chronic Lymphocytic Leukemia (CLL) – This is most common among adults over 55, although younger adults can get it as well. CLL hardly ever affects children. The majority of patients with CLL are men, over 60%. 75% of treated CLL patients survive for over five years. Experts say CLL is incurable. A more aggressive form of CLL is B-cell prolymphocytic leukemia.
Acute Myelogenous Leukemia (AML) – AML is more common among adults than children, and affects males significantly more often than females. Patients are treated with chemotherapy. 40% of treated patients survive for over 5 years. The following are subtypes of AMS – acute promyelocytic leukemia, acute myeloblastic leukemia, and acute megakaryoblastic leukemia.
Chronic Myelogenous Leukemia (CML) – The vast majority of patients are adults. 90% of treated patients survive for over 5 years. Gleevec (imatinib) is commonly used to treat CML, as well as some other drugs. Chronic monocytic leukemia is a subtype of CML.
Click here to read about leukemia in more detail.
Sources: Seattle Genetic, Inc., Medical News Today Archives
Written by Christian Nordqvist