A Phase I Dose Escalation Trial of Clofarabine in Addition to Topotecan, Vinorelbine, Thiotepa, and Dexamethasone in Pediatric Patients With Relapsed or Refractory Acute Leukemia
- Determine the maximum tolerated dose of clofarabine when administered in combination
with topotecan hydrochloride, vinorelbine ditartrate, thiotepa, and dexamethasone in
young patients with relapsed or refractory acute leukemia.
- Evaluate the antileukemic potential of this regimen in these patients.
- Evaluate the incidence and severity of treatment-related morbidity and mortality in
patients treated with this regimen.
- Develop a new reinduction treatment regimen that will result in a patient clinical
response with as little residual disease as possible to permit a bone marrow
transplantation while in subsequent remission; maintain the response long enough to
identify an appropriate stem cell donor; and permit the patient to undergo a stem cell
transplantation free of infections and without vital organ dysfunction.
OUTLINE: This is a nonrandomized, prospective, dose-escalation study of clofarabine.
Patients receive topotecan hydrochloride IV continuously over 120 hours on days 0-4;
vinorelbine ditartrate over 6-10 minutes on days 0, 7, and 14; thiotepa IV over 4 hours on
day 2; clofarabine IV over 2 hours on days 3-7; and oral or IV dexamethasone 3 times daily
on days 3 and 7-13 and then on day 3 only thereafter. Patients also receive filgrastim
(G-CSF) subcutaneously once daily beginning on day 8 and continuing until blood counts
recover. Treatment repeats every 21 days in the absence of disease progression or
Cohorts of 3-6 patients receive escalating doses of clofarabine until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience
dose-limiting toxicity OR the dose preceding that at which 2 of 3 patients experience
dose-limiting toxicity. At least 6 patients are treated at the MTD.
After completion of study treatment, patients are followed once a week for 4 weeks, twice a
month for 6 months, and then once a month for 2 years.
PROJECTED ACCRUAL: A total of 23 patients will be accrued for this study.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of clofarabine
Peter G. Steinherz, MD
Memorial Sloan-Kettering Cancer Center
United States: Institutional Review Board
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|