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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


Phase 1
N/A
28 Years
Open (Enrolling)
Both
Leukemia

Thank you

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 CenterNew York, New York  10021