Phase II Study of Oral Clofarabine in Myelodysplastic Syndrome (MDS)
Clofarabine is a new chemotherapy drug that is designed to interfere with the growth and
development of cancer cells.
If you are found to be eligible, you will be randomly assigned (as in the roll of dice) to
one of 2 treatment groups. Participants in Group 1 will take a lower dose of clofarabine
than Participants in Group 2. You have an equal chance of being assigned to either of the 2
treatment groups. Neither you nor your study doctor can choose your assignment. Later
(after the first 40 patients), the assignment will favor the better treatment arm until one
arm is selected as the significantly better one, or until 80 patients are treated in total.
When you have been assigned to a treatment group, you will receive clofarabine as tablets
once a day for 5 days in a row. This will be repeated every 4-8 weeks. Each 4-8 week
period is considered 1 cycle of treatment.
Original patients who are still on study (original patients who received or are still
receiving 30 mg/m2) have already been reduced to lower doses on subsequent courses or had
treatment discontinued/completed. These patients will be asked to sign a new informed
consent document to be made aware of the new developments in this study.
Each dose of clofarabine should be taken with 4 ounces of water in the morning, on an empty
stomach. You must not eat or drink anything besides water from midnight the night before
you take the study drug until 1 hour after taking the morning dose. You should take
clofarabine every morning at about the same time. If vomiting occurs within 15 minutes of
taking clofarabine, the dose may be repeated. If vomiting occurs more than 15 minutes after
taking clofarabine, the dose cannot be replaced or made up.
Coffee and other caffeinated liquids cannot be taken before dosing and for 1 hour after
All clofarabine doses should be taken either in the outpatient or inpatient setting by
qualified and trained site personnel or given with appropriate instructions to you and/or
your care provider to take at home. At the start of each cycle, you will receive enough
clofarabine for 1 cycle of therapy. You should store the clofarabine in its original
container at room temperature. You should keep the container closed when not in use, and
out of the reach of children.
After each cycle of therapy, you will not receive the next cycle of chemotherapy until your
blood counts have recovered and any possible side effects have gone away (for around 4 to 8
weeks). You must stay in Houston for the first treatment cycle (about 4 to 8 weeks) and will
be required to return to Houston before receiving each additional cycle of chemotherapy (up
to 6 days each cycle).
Before every treatment cycle, your doctor will perform a physical exam, including
measurement of your weight and vital signs (blood pressure, heart rate, temperature, and
breathing rate). You will be asked about the level of your daily activities and how you are
feeling. You will have blood samples (about 1-2 teaspoons) collected for routine lab tests
1-2 times a week for the first cycle, then every 2-4 weeks while on therapy. Repeat bone
marrow samples will be collected every 1-3 cycles. However, if you complete the study before
the third cycle, the bone marrow may be taken then. You may choose to have check-up visits
and blood tests with your local doctor.
If you show a response and do not experience any severe side effects, you can receive up to
a total of 12 cycles of therapy. During each cycle, clofarabine will be given the same way
as during the first cycle. However, the dose of clofarabine may be lowered during later
cycles to decrease the risk of side effects that may have occurred in previous cycles. If
the disease gets worse or you experience any intolerable side effects, you will be taken off
the study and your doctor will discuss other treatment options with you.
This is an investigational study. Clofarabine given by vein is approved by the FDA for
treatment of pediatric acute lymphoblastic leukemia. Its use in this study is experimental.
Up to 80 patients will take part in this study. All will be enrolled at MD Anderson.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Complete Response Rate (CR Rate)
Response rate is calculated as number of participants with Complete Remission (CR) divided by total number of participants after 3 courses of oral clofarabine therapy where CR is Normalization of the peripheral blood and bone marrow with <5% bone marrow blasts, a peripheral blood granulocyte count > (1.0 x 109/ L, and a platelet count > 100 x 109/L). Monitored using the Bayesian approach of Thall, Simon, Estey (1995, 1996) and the extension by Thall and Sung (1998).
After 3 courses of therapy
Hagop Kantarjian, MD
M.D. Anderson Cancer Center
United States: Food and Drug Administration
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