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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00462787
• Other study ID #: 07-012
• Secondary ID: MSKCC-07012
• Status: Completed
• Phase: Phase 1
• First received: April 18, 2007
• Last updated: November 13, 2013
• Start date: April 2007
• Est. completion date: November 2013

Study information

• Verified date: November 2013
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 28 Years

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia

Intervention

Biological:
• filgrastim

Drug:
• clofarabine

• dexamethasone

• thiotepa

• topotecan hydrochloride

• vinorelbine tartrate

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of clofarabine		2 years	Yes
Primary	Overall survival		2 years	No
Primary	Progression-free survival		2 years	No