Combination Chemotherapy in Treating Young Patients With Relapsed or Refractory Acute Leukemia

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00462787
First received: April 18, 2007
Last updated: November 13, 2013
Last verified: November 2013

April 18, 2007
November 13, 2013
April 2007
November 2013   (final data collection date for primary outcome measure)
  • Maximum tolerated dose of clofarabine [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Maximum tolerated dose of clofarabine
  • Overall survival
  • Progression-free survival
Complete list of historical versions of study NCT00462787 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Combination Chemotherapy in Treating Young Patients With Relapsed or Refractory Acute Leukemia
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

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.

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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Leukemia
  • Biological: filgrastim
  • Drug: clofarabine
  • Drug: dexamethasone
  • Drug: thiotepa
  • Drug: topotecan hydrochloride
  • Drug: vinorelbine tartrate
Experimental: Clofarabine
This is a single arm phase I clinical trial to assess safety (morbidity and mortality) of a novel leukemia re-induction regimen. The first component of this trial is a phase I dose escalation study to determine the maximum tolerated dose (MTD) of the novel agent Clofarabine, when used in combination with topotecan, vinorelbine, thiotepa and dexamethasone. A total of three dose levels will be explored in this study.
Interventions:
  • Biological: filgrastim
  • Drug: clofarabine
  • Drug: dexamethasone
  • Drug: thiotepa
  • Drug: topotecan hydrochloride
  • Drug: vinorelbine tartrate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
23
November 2013
November 2013   (final data collection date for primary outcome measure)

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
Both
up to 28 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00462787
07-012, MSKCC-07012
Not Provided
Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Peter G. Steinherz, MD Memorial Sloan-Kettering Cancer Center
Principal Investigator: Neerav Shukla, MD Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP