Phase I/II Study of Clofarabine Plus Cyclophosphamide for Relapsed and Refractory Acute Lymphoblastic Leukemia (ALL)
Clofarabine is a drug that is designed to interfere and disrupt important metabolic pathways
of cancer cells by interfering with their multiplication and slowing or stopping their
growth. Cyclophosphamide is also designed to destroy cancer cells by interfering with their
multiplication and slowing or stopping their growth and spread throughout the body.
Cyclophosphamide is commonly used in the treatment of ALL.
If you are found to be eligible to take part in this study, you will receive clofarabine by
vein over about 60 minutes, once a day for 3 to 5 days. Cyclophosphamide will be given by
vein over about 3 hours, twice a day for 3 to 5 days. These 3-5 days are considered 1 cycle
As the safety of this combination has not been established yet, at least the first 2
participants on this study will receive clofarabine for 3 days and cyclophosphamide at a
lower dose than usually given for 3 days (6 doses). Should there be no serious side effects
that can be related to the study drugs, the next group of 2 participants will receive
clofarabine over 3 days and a slightly higher dose of cyclophosphamide for 3 days (6 doses).
Should there still be no serious side effects at that level, 2 further levels will be tested
where both clofarabine and cyclophosphamide are then given over 4 days and eventually 5
days. Should serious and study drug-related side effects occur at any point during this
increase of doses, a certain dose level along this increase will be defined as the
appropriate dose for all future participants to receive. It is estimated that about 30
participants will receive therapy during the dose escalations portion of this study (Phase
I). It is estimated that about 25 more participants will receive therapy at the dose
levels that are considered best (Phase II).
During treatment, you will have a physical exam at least once a week. You may also be asked
about the level of your daily activities, how you are feeling, and which medications you are
taking currently. Routine blood samples (about 1 tablespoon each) will be drawn at least 1-3
times weekly and more frequently if considered necessary. A bone marrow aspirate and/or
biopsy will be repeated starting at about Day 14 and will be repeated every 1 to 2 weeks
until the study doctors can decide for sure whether you have responded or not. In some
cases, a repeat bone marrow test may not be necessary, but this decision will be made by
your treating doctor.
If you respond well after your first round of therapy, you may receive up to 6 additional
courses of therapy. Each course will be repeated about every 3 to 7 weeks at a slightly
lower dose of both drugs than was used during the first round of therapy. Later doses can
also be changed depending on what type of side effects you may experienced with earlier
rounds of therapy.
At the end of the study, a heart scan (either an Echo or MUGA scan) will be repeated. About
1 tablespoon of blood will be taken for routine blood tests. A focused physical exam may
also be repeated.
This is an investigational study. All drugs in this study are FDA approved and commercially
available. Their use together in this study is investigational. . About 55 patients will
take part in this study. All will be enrolled at M. D. Anderson.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose for Cyclophosphamide (MTD)
MTD is dose at which there are no dose limiting toxicity (DLT) defined as any =/> grade 3 drug-related non-hematologic toxicity that occurs within the first 14 days after start of treatment. Evaluation using continual reassessment method; 3-5 Day Cycle
First 14 days of each cycle
Stefan Faderl, MD
M.D. Anderson Cancer Center
United States: Food and Drug Administration
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