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

Registration Number
NCT00462787
Lead Sponsor
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.

Detailed Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
23
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
ClofarabineclofarabineThis 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.
Clofarabinetopotecan hydrochlorideThis 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.
Clofarabinevinorelbine tartrateThis 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.
ClofarabinefilgrastimThis 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.
ClofarabinedexamethasoneThis 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.
ClofarabinethiotepaThis 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.
Primary Outcome Measures
NameTimeMethod
Maximum tolerated dose of clofarabine2 years
Progression-free survival2 years
Overall survival2 years
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Memorial Sloan-Kettering Cancer Center

🇺🇸

New York, New York, United States

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