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

This study has been completed.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center Identifier:
First received: April 18, 2007
Last updated: November 13, 2013
Last verified: November 2013

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 Intervention Phase
Biological: filgrastim
Drug: clofarabine
Drug: dexamethasone
Drug: thiotepa
Drug: topotecan hydrochloride
Drug: vinorelbine tartrate
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

Further study details as provided by Memorial Sloan Kettering Cancer Center:

Primary Outcome Measures:
  • 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 ]

Enrollment: 23
Study Start Date: April 2007
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.


Ages Eligible for Study:   up to 28 Years
Genders Eligible for Study:   Both
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
  Contacts and Locations
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Please refer to this study by its identifier: NCT00462787

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)
Principal Investigator: Peter G. Steinherz, MD Memorial Sloan Kettering Cancer Center
Principal Investigator: Neerav Shukla, MD Memorial Sloan Kettering Cancer Center
  More Information

Responsible Party: Memorial Sloan Kettering Cancer Center Identifier: NCT00462787     History of Changes
Other Study ID Numbers: 07-012  MSKCC-07012 
Study First Received: April 18, 2007
Last Updated: November 13, 2013
Health Authority: United States: Institutional Review Board

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:
Neoplasms by Histologic Type
BB 1101
Dexamethasone 21-phosphate
Dexamethasone acetate
Alkylating Agents
Anti-Inflammatory Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action processed this record on May 04, 2016