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
N/A
28 Years
Both
Leukemia
Trial Information
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
OBJECTIVES:
- 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
unacceptable toxicity.
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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Must have 1 of the following diagnoses:
- Acute lymphoblastic leukemia (ALL) meeting 1 of the following criteria:
- Refractory to initial induction with two or more standard regimens
- Relapsed < 24 months after first complete response on a high-risk protocol
OR refractory to one standard reinduction regimen
- Second or greater relapse
- Acute myeloid leukemia, acute biphenotypic leukemia, or acute undifferentiated
leukemia meeting 1 of the following criteria:
- Refractory to initial induction
- First or greater relapse
- Must have > 20% bone marrow blasts, or evidence of recurrent disease at an
extramedullary site
- No symptomatic CNS disease
- Patients with asymptomatic CNS disease are eligible with the approval of the
principal investigator
PATIENT CHARACTERISTICS:
- Karnofsky performance status (PS) 70-100% OR Lansky PS 70-100%
- AST and ALT < 4 times upper limit of normal
- Bilirubin < 2.0 mg/dL (unless liver involvement)
- Creatinine within normal range for age OR creatinine clearance > 60 mL/min/1.73 m^2
- Adequate cardiac function (either asymptomatic with no prior risk factors, or if
symptomatic, left ventricular ejection fraction > 50% at rest)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No active uncontrolled viral, bacterial, or fungal infection
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior clofarabine
- More than 2 weeks since prior systemic chemotherapy
- At least 7 days since prior chemotherapy for patients with rapidly progressive
disease and recovered
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose of clofarabine
Outcome Time Frame:
2 years
Safety Issue:
Yes
Principal Investigator
Peter G. Steinherz, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Memorial Sloan-Kettering Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
07-012
NCT ID:
NCT00462787
Start Date:
April 2007
Completion Date:
April 2013
Related Keywords:
- Leukemia
- acute undifferentiated leukemia
- recurrent childhood acute lymphoblastic leukemia
- recurrent childhood acute myeloid leukemia
- recurrent adult acute lymphoblastic leukemia
- recurrent adult acute myeloid leukemia
- Leukemia
Name | Location |
|---|---|
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
