This phase 2 clinical trial will test the effectiveness of a combination treatment, consisting of ibrutinib (Imbruvica), fludarabine (Fludara), cyclophosphamide (Cytoxan), and obinutuzumab (Gazyva), in treating chronic lymphocytic leukemia (CLL). The primary outcome will be measured by the response to treatment. This trial is being conducted at the University of Texas MD Anderson Cancer Center in Houston, Texas.
The details
Ibrutinibis a drug that stops the growth of B-cells and may decrease the spread of CLL. It permanently binds to the Bruton's tyrosine kinase (BTK), a protein essential for B-cell growth and development. Since cancerous lymphocytes rely on B-cell signals to develop, blocking BTKs could stop the spread of cancer. Fludarabine and cyclophosphamide are chemotherapy drugs often used to treat lymphocytic leukemia. They work by damaging DNA and inhibiting (blocking) DNA synthesis or repair in blood cells, which leads to cell death. Obinutuzumab is an immunotherapy that uses the body’s own immune system to identify and kill cancerous B-lymphocytes (and B-cells). It is an antibody (protein in the immune system) that binds to a protein found on the lymphocytes, which alerts other parts of the immune system to attack. It is unclear whether the combination of drugs will improve disease conditions.
The study will examine the effectiveness of the combination of the four treatements. The main outcome to be measured is the number of patients with complete remission and minimal residual disease (small number of cancer cells remain).
Who are they looking for?
This trial is recruiting 45 patients with CLL who have the IGHV mutation and have not yet been treated. Patients should not have had major surgery within 3 weeks prior to enrollment. Participants should not have significant cardiovascular disease or history of stroke within 6 months of the trial.
Participants should not have any active infections. Both male and female participants will need to use contraception for up to 30 days after the last treatment.
How will it work
Patients will be given obinutuzumab intravenously (through IV into a vein) on days 1, 2, 8, and 15 of the first 28-day cycle, and day 1 of cycles 2 and 3. Fludarabine will be administered intravenously on days 2-4 of cycle 1 and days 1-3 of cycles 2 and 3. Intravenous cyclophosphamide will be given on days 2-4 of cycle 1, and days 1-3 of cycles 2 and 3. Ibrutinib will be taken by mouth every day during cycles 1-3. Other treatments required are allopurinol (Zyloprim) and valacyclovir (Valtrex) to lower the risk of side effects.
Treatment following cycle 3 will vary based on response.
