Phase I Dose-Escalation Trial of Clofarabine Followed by Escalating Doses of Fractionated Cyclophosphamide in Adults and Children With Relapsed or Refractory Acute Leukemias
- Determine the feasibility and tolerability of administering clofarabine and
fractionated cyclophosphamide in patients with relapsed or refractory acute leukemia,
chronic myelogenous leukemia, or high-risk myeloproliferative disorders
- Determine the maximum tolerated dose of clofarabine and fractionated cyclophosphamide
in these patients.
- Determine the toxic effects of these drugs in these patients.
- Obtain preliminary data of biologic and pharmacodynamic effects of this regimen on
marrow and circulating leukemic blasts in these patients.
OUTLINE: This is a dose-escalation study. Patients are stratified according to age (adult vs
Patients receive cyclophosphamide IV over 2 hours on day 0. Patients then receive
clofarabine IV over 2 hours and cyclophosphamide IV over 2 hours on days 1-3 and 8-10.
Treatment with clofarabine and cyclophosphamide repeats every 28 days for at least 2 courses
in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of clofarabine and cyclophosphamide until
the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding
that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 10
patients are treated at the MTD.
After completion of study treatment, patients are followed periodically for 1 year.
PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study.
Primary Purpose: Treatment
Judith E. Karp, MD
Sidney Kimmel Comprehensive Cancer Center
United States: Institutional Review Board
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|