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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00462787
Recruitment Status : Completed
First Posted : April 19, 2007
Last Update Posted : November 14, 2013
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Leukemia Biological: filgrastim Drug: clofarabine Drug: dexamethasone Drug: thiotepa Drug: topotecan hydrochloride Drug: vinorelbine tartrate Phase 1

Detailed Description:


  • 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : April 2007
Actual Primary Completion Date : November 2013
Actual Study Completion Date : November 2013

Arm Intervention/treatment
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.
Biological: filgrastim
Drug: clofarabine
Drug: dexamethasone
Drug: thiotepa
Drug: topotecan hydrochloride
Drug: vinorelbine tartrate

Primary Outcome Measures :
  1. Maximum tolerated dose of clofarabine [ Time Frame: 2 years ]
  2. Overall survival [ Time Frame: 2 years ]
  3. Progression-free survival [ Time Frame: 2 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   up to 28 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00462787

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United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
National Cancer Institute (NCI)
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Principal Investigator: Peter G. Steinherz, MD Memorial Sloan Kettering Cancer Center
Principal Investigator: Neerav Shukla, MD Memorial Sloan Kettering Cancer Center
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Responsible Party: Memorial Sloan Kettering Cancer Center Identifier: NCT00462787    
Other Study ID Numbers: 07-012
First Posted: April 19, 2007    Key Record Dates
Last Update Posted: November 14, 2013
Last Verified: November 2013
Keywords provided by Memorial Sloan Kettering Cancer Center:
acute undifferentiated leukemia
recurrent childhood acute lymphoblastic leukemia
recurrent childhood acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
Additional relevant MeSH terms:
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Neoplasms by Histologic Type
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Alkylating
Alkylating Agents