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Alemtuzumab - Campath®                                                                                                                                                                                                           

An humanized monoclonal antibody that selectively binds to CD52, a protein found on the surface of normal and malignant B and T cells, that is used to reduce the numbers of circulating malignant cells of patients who have B-cell chronic lymphocytic leukemia (B-CLL).

Produced in the laboratory using genetically engineered single clones alemtuzumab is a humanized antibody, meaning that the regions that bind CD52, located on the tips of the Y branches, are derived from rat antibodies, but the rest of the antibody is human sequence.

 

Disorders such as Rheumatoid Arthritis and Vasculitis received the attention of Campath during the early 1990’s, following on from this line of research secondary progressive and early relapsing-remitting MS received the attention of Campath. During a clinical trial of Campath some patients demonstrated a reduction in disabling relapses as compared to a standard MS drug. In 2005 one patient receiving Campath died of bleeding in the brain, the clinical testing was suspended and a surveillance system used to watch for symptoms of the bleeding disorder. Five further cases of the bleeding disorder, called immune throbocytopedia purpura (ITP) were uncovered and treated.

 

The parent company considers it to be a “manageable risk” for Campath patients. (If ITP is detected early enough it can be treated?)

 

Side effects may occur                                                                                                                                                                                                                

• Fever and chills
• Nausea and vomiting
• Diarrhoea
• Shortness of breath
• Skin rash
• Transiently worsen MS symptoms.
• Unusual fatigue
• Low blood pressure (hypotension).

 

Adverse side effects may occur                                                                                                                                                                                                

• Possible depletion of one or more types of blood cells.
• Risk of ITP
• Because CD52 is expressed on a patient's normal B and T cells, as well as on the surface of the abnormal B cells the treatment eliminates both normal and cancerous cells.
• The treatment also seems to trigger autoimmune reactions against various other blood cells. This results in severe reduction of the many circulating blood cells including red blood cells (anemia), white blood cells (neutropenia), and clotting cells (thrombopenia). These conditions are treated with blood transfusions. The great majority of patients treated exhibit some type of blood cell depletion.
• Prevalence of opportunistic infections that occurs during the treatment. Serious, and sometimes fatal bacterial, viral, fungal, and protozoan infections have been reported. Treatments to prevent pneumonia and herpes infections reduce, but do not eliminate these infections.
• In patients with high tumour burden (a large number of circulating malignant B cells) this drug can cause a tumour lysis syndrome thought to be due to the release of the lysed cells' contents into the blood stream, it can cause a misbalance of urea, uric acid, phosphate, potassium, and calcium in the urine and blood. Patients at risk from this adverse side effect must keep hydrated and can be given allopurinol before infusion.
• Auto-immune diseases have developed during the use of Campath, the most common was Graves disease (over active thyroid). This occurred in 30% of of people treated with Campath. One person developed a serious form of auto-immunity disease which damaged their kidneys leading to the need for dialysis and a kidney transplant.

 

Acetominophen and diphenhydramine hydrochoride are given thirty to sixty minutes before the infusion to help reduce side effects.

 

Additionally, patients generally receive anti-infective medication before treatment to help minimize the serious opportunistic infections that can result from this treatment. Specifically;

• Trimethoprim/sulfamethoxazole (to prevent bacterial infections)
• famciclovir (to prevent viral infections)

Used during the clinical trial to decrease infections, although they were not eliminated.

 

Precautions                                                                                                                                                                                                                                  

Blood studies should be done on a weekly basis while patients are receiving the alemtuzumab treatment. Vaccination during the treatment session is not recommended, given the T cell depletion that occurs during treatment. Furthermore, given that antibodies like alumtuzumab can pass through the placenta to the developing fetus and in breast milk, use during pregnancy and breastfeeding is not recommended unless clearly needed.

 

Note - The exposure of young people to a potentially toxic drug may be a problem amongst people suffering from early relapsing-remitting MS.

 

Interactions                                                                                                                                                                                                                                   

To date (2008)There have been no formal drug interaction studies done for alemtuzumab - Campath.

 

Recommended dosage:

This antibody should be administered in a gradually escalating pattern at the start of treatment and any time administration is interrupted for seven or more days. The recommended beginning dosage for B-CLL patients is a daily dose of 3 mg of Campath administered as a two-hour IV infusion. Once this amount is tolerated, the dose is increased to 10 mg per day. After tolerating this dose, it can be increased to 30 mg, administered three days a week.

Source - Gale Encyclopedia of Medicine, Published December, 2002 by the Gale Group The Essay Author is Michelle Johnson, MS, JD.

 

Alemtuzumab is approved for the treatment of chronic lymphocytic leukemia (CLL). It's thought to work by targeting and destroying certain immune cells that normally protect against infection but are believed to be damaged in MS and other autoimmune diseases, resulting in the destruction of healthy tissue.

 

 

                                                                                                                                                                                                                                           

1. Idiopathic thrombocytopenic purpura (ITP). A bleeding condition in which the blood doesn’t clot as it should. This is due to a low number of blood cells called platelets Platelets are made in your bone marrow (along with other kinds of blood cells). Platelets circulate through the blood vessels and help stop bleeding by sticking together (clotting) to seal small cuts or breaks.
2. Idiopathic  means that the cause of the disease  isn’t known. Thrombocytopenic means there is a lower-than-normal number of platelets in the blood. Purpura are purple bruises caused by bleeding under the skin. People with ITP may have nosebleeds, bleeding from the gums or other bleeding that’s hard to stop. Bleeding if it occurs in the brain as a result of ITP can be life threatening. If you have ITP, your immune system attacks and destroys its own platelets.
3. There are two types of ITP acute  and chronic

• Acute ITP generally lasts less than 6 months. It mainly occurs in children, both boys and girls, and is the most common type of ITP. It often occurs after an infection caused by a virus.
• Chronic ITP is long-lasting (6 months or longer) and mostly affects adults. Chronic ITP affects women 2 to 3 times more often than men.
•  Treatment depends on how severe the bleeding symptoms are and the platelet count.

1. Alkylating agent - A chemical that alters the composition of the genetic material of rapidly dividing cells, such as cancer cells, causing selective cell death; used as a chemotherapeutic agent to treat B-CLL.
2. Antibody - A protective protein made by the immune system in response to an antigen, also called an immunoglobulin.
3. Autoimmune - An immune reaction of a patient against their own cells.
4. Humanization - Fusing the constant and variable framework region of one or more human immunoglobulins with the binding region of an animal immunoglobulin, done to reduce human reaction against the fusion antibody.
5. Monoclonal - Genetically engineered antibodies specific for one antigen.
6. Tumor lysis syndrome - A side effect of some immunotherapies, like monoclonal antibodies, that lyse the tumor cells, due to the toxicity of flooding the bloodstream with such a quantity of cellular contents.

 

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