Combination Chemotherapy in Treating Young Patients With Relapsed or Refractory Acute Leukemia
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on December 08, 2011
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Leukemia
Intervention: filgrastim (Biological); clofarabine (Drug); dexamethasone (Drug); thiotepa (Drug); topotecan hydrochloride (Drug); vinorelbine tartrate (Drug)
Phase: Phase 1
Sponsored by: Memorial Sloan-Kettering Cancer Center
Official(s) and/or principal investigator(s):
Peter G. Steinherz, MD, Principal Investigator, Affiliation: Memorial Sloan-Kettering Cancer Center
Neerav Shukla, MD, Principal Investigator, Affiliation: Memorial Sloan-Kettering Cancer Center
RATIONALE: Drugs used in chemotherapy, such as clofarabine, topotecan, vinorelbine,
thiotepa, and dexamethasone, work in different ways to stop the growth of cancer cells,
either by killing the cells or by stopping them from dividing. Giving more than one drug
(combination chemotherapy) may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of clofarabine when
given together with topotecan, vinorelbine, thiotepa, and dexamethasone in treating young
patients with relapsed or refractory acute leukemia.
Official title: 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
Study design: Allocation: Non-Randomized, Primary Purpose: Treatment
Maximum tolerated dose of clofarabine
- 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.
Minimum age: N/A.
Maximum age: 28 Years.
- 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
- No symptomatic CNS disease
- Patients with asymptomatic CNS disease are eligible with the approval of the
- 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
Locations and Contacts
Memorial Sloan-Kettering Cancer Center, New York, New York 10065, United States; Recruiting
Peter G. Steinherz, MD, Phone: 212-639-7951
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: April 2007
Last updated: February 23, 2011