A Study of Clofarabine in Combination With Etoposide and Cyclophosphamide in Children With Acute Leukemias.

NCT ID: NCT00315705

Last Updated: 2014-04-14

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-03-31

Study Completion Date

2010-05-31

Brief Summary

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Clofarabine (injection) is approved by the Food and Drug Administration (FDA) for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia (ALL) who have had at least 2 prior treatment regimens. This use is based on the induction of complete responses. Randomized trials demonstrating increased survival or other clinical benefit have not been conducted.

The purpose of the phase 1 portion of this study was to determine if clofarabine added to a combination of etoposide and cyclophosphamide is safe in children with relapsed or refractory acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML). The purpose of the phase 2 portion of the study was to measure the effectiveness of the combination therapy in children with ALL.

Detailed Description

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Conditions

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Acute Lymphoblastic Leukemia Acute Myelogenous Leukemia Relapsed Leukemia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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clofarabine, etoposide, cyclophosphamide

Phase 1: escalating dosage of the three drugs delivered intravenously. Clofarabine dosage from 20-40 mg/m\^2, etoposide dosage from 75-100 mg/m\^2, cyclophosphamide dosage from 340-440 mg/m\^2.

Phase 2: The recommended phase 2 doses (RP2D) were clofarabine 40 mg/m\^2, etoposide 100 mg/m\^2 and cyclophosphamide 440 mg/m\^2 delivered intravenously

Group Type EXPERIMENTAL

clofarabine

Intervention Type DRUG

Clofarabine 20-40 mg/m²/day 2 hour intravenous (IV) infusion daily for 5 days of a 28 day cycle as the first of the three IV interventions administered. Maximum of 8 cycles given in both the phase 1 and phase 2 study periods.

Etoposide

Intervention Type DRUG

Etoposide 75-100 mg/m²/day 2 hour intravenous (IV) infusion daily for 5 days of a 28 day cycle following clofarabine therapy. Maximum of 8 cycles given in both the phase 1 and phase 2 study periods.

Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide 340-440 mg/m²/day as 30-60 minute intravenous (IV) infusion daily for 5 days of a 28 day cycle following the other two interventions. Maximum of 8 cycles given in both the phase 1 and phase 2 study periods.

Interventions

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clofarabine

Clofarabine 20-40 mg/m²/day 2 hour intravenous (IV) infusion daily for 5 days of a 28 day cycle as the first of the three IV interventions administered. Maximum of 8 cycles given in both the phase 1 and phase 2 study periods.

Intervention Type DRUG

Etoposide

Etoposide 75-100 mg/m²/day 2 hour intravenous (IV) infusion daily for 5 days of a 28 day cycle following clofarabine therapy. Maximum of 8 cycles given in both the phase 1 and phase 2 study periods.

Intervention Type DRUG

Cyclophosphamide

Cyclophosphamide 340-440 mg/m²/day as 30-60 minute intravenous (IV) infusion daily for 5 days of a 28 day cycle following the other two interventions. Maximum of 8 cycles given in both the phase 1 and phase 2 study periods.

Intervention Type DRUG

Other Intervention Names

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Clolar Evoltra Eposin Endoxan Revimmune Cytoxan

Eligibility Criteria

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Inclusion Criteria

* NOTE: the following eligibility criteria were applicable to acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) patients for the Phase 1 portion of this study, and to ALL patients for the Phase 2 portion of the study (only ALL patients were allowed in the Phase 2 portion of the study).
* ALL with \> 25% blasts in bone marrow; AML with ≥ 5% blasts in bone marrow; ALL and AML patients may have extramedullary disease
* Karnofsky Performance Status ≥ 50 for patients \> 10 years old; Lansky Performance Status ≥ 50 for patients ≤ 10 years old
* Prior therapy: AML: 1-2 prior induction regimens and ≤ 1 hematopoietic stem cell transplant (HSCT); ALL: 1-3 prior induction regimens
* Adequate liver, renal, pancreatic, and cardiac function
* Have received no prior HSCT (study amended in Phase 2 to exclude patients with prior HSCT)

Exclusion Criteria

* NOTE: the following eligibility criteria were applicable to ALL and AML patients for the Phase 1 portion of this study, and to ALL patients for the Phase 2 portion of the study (only ALL patients were allowed in the Phase 2 portion of the study).
* Burkitt's leukemia
* Previous treatment with clofarabine
* Uncontrolled systemic fungal, bacterial or other infection and 48 hrs negative blood cultures required for patients with a history of fever within 3 days of enrollment
* Active CNS involvement (i.e., should be CNS1 or CNS2)
* Inadequate time since last therapy: ≤ 14 days since last cytotoxic chemotherapy; ≤ 7 days since last biologic therapy; ≤ 14 days since last monoclonal antibody therapy
* Have received prior HSCT (study amended in Phase 2 to exclude patients with prior HSCT)
* Pregnant or lactating
* Have tested positive for hepatitis B or hepatitis C infection or history of cirrhosis
Minimum Eligible Age

1 Year

Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Monitor

Role: STUDY_DIRECTOR

Genzyme, a Sanofi Company

Locations

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Children's Hospital of Alabama

Birmingham, Alabama, United States

Site Status

Children's Hospital of Los Angeles

Los Angeles, California, United States

Site Status

Rady Children's Hospital

San Diego, California, United States

Site Status

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Site Status

Children's Memorial Hospital

Chicago, Illinois, United States

Site Status

St. Vincent Children's Hospital

Indianapolis, Indiana, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Children's Hospital of Michigan

Detroit, Michigan, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

New York School of Medicine

New York, New York, United States

Site Status

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Hijiya N, Thomson B, Isakoff MS, Silverman LB, Steinherz PG, Borowitz MJ, Kadota R, Cooper T, Shen V, Dahl G, Thottassery JV, Jeha S, Maloney K, Paul JA, Barry E, Carroll WL, Gaynon PS. Phase 2 trial of clofarabine in combination with etoposide and cyclophosphamide in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. Blood. 2011 Dec 1;118(23):6043-9. doi: 10.1182/blood-2011-08-374710. Epub 2011 Oct 3.

Reference Type DERIVED
PMID: 21967976 (View on PubMed)

Other Identifiers

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CLO21800205

Identifier Type: -

Identifier Source: org_study_id

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