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Phase I Dose-Escalation Trial of Clofarabine Followed by Escalating Doses of Fractionated Cyclophosphamide in Children With Relapsed or Refractory Acute Leukemias

Information source: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Myelodysplastic Syndrome; Acute Myeloid Leukemia; Myeloproliferative Disorders; Acute Lymphocytic Leukemia; Acute Promyelocytic Leukemia; Acute Leukemia; Chronic Myelogenous Leukemia; Myelofibrosis; Chronic Myelomonocytic Leukemia; Juvenile Myelomonocytic Leukemia

Intervention: Clofarabine (Drug); Cyclophosphamide (Drug)

Phase: Phase 1

Status: Active, not recruiting

Sponsored by: Sidney Kimmel Comprehensive Cancer Center

Summary

This is a Phase I study designed to determine the MTD and assess the toxicity associated with clofarabine followed by fractionated cyclophosphamide in patients > 1 year of age or < 21 years of age with relapsed or refractory acute leukemias. There will be 25 to 35 patients enrolled. Cohorts of 3 to 6 patients each will receive escalated doses of clofarabine followed by fractionated cyclophosphamide until the MTD is reached. There will be no intra-patient dose escalation. Single-agent cyclophosphamide will be administered by 2-hour IVI on Day 0 of cycle 1. On Days 1, 2, and 3 and Days 8, 9, and 10 clofarabine will be administered by IVI 2 hours before each dose of cyclophosphamide (see the treatment schema below). A cycle is defined as 28 days.

Clinical Details

Official title: Phase I Dose-Escalation Trial of Clofarabine Followed by Escalating Doses of Fractionated Cyclophosphamide in Children With Relapsed or Refractory Acute Leukemias

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: To determine the feasibility, tolerability, toxicities, and MTD of clofarabine followed by fractionated cyclophosphamide in pediatric patients with relapsed or refractory acute leukemias.

Secondary outcome: To obtain preliminary descriptive data of the biologic and pharmacodynamic effects of clofarabine followed by fractionated cyclophosphamide on marrow and circulating leukemic blasts in pediatric patients with relapsed or refractory acute leukemias.

Eligibility

Minimum age: 1 Year. Maximum age: 21 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 for

adolescent/young adult patients.

- Lansky Performance Index > 50 for pediatric patients less than age 10 years.

- Laboratory values obtained < 7 days prior to receiving study treatment:

- Total bilirubin < 1. 5 mg/dL unless elevated due to hemolysis. The conjugated serum

bilirubin prior to study entry must be within the normal range.

- Aspartate transaminase (AST) and alanine transaminase (ALT) < 2. 5 × upper limit of

normal (ULN)

- Serum creatinine < 1. 0 mg/dL in adolescent/young adults (patients 12 to 17 years of

age). For pediatric patients with serum creatinine above the ULN, creatinine clearance > 90 ml/min/1. 73m2 calculated using the Schwartz formula may be enrolled. Collected creatinine clearance may be substituted. Patients 18 years and older (Adult population): Serum creatinine <1. 0 mg/dL; if serum creatinine >1. 0 mg/dL, then the estimated glomerular filtration rate (GFR) must be >60 mL/min/1. 73 m2

- Cardiac function must be normal per the institution normal as measured by

echocardiogram (ECHO) within 7 days.

- Patients should have no evidence of myositis as detected by abnormal serum creatine

kinase and/or myoglobin. Exclusion Criteria:

- No chemotherapy, radiation, or major surgery within 2 weeks prior to first dose of

study drug except for 5-azacytidine, thalidomide, hydroxyurea, imatinib (Gleevec), and interferon which must be discontinued at least 3 days before study entry and the patient should have recovered from the toxic side effects of such therapy. In the instance of progressive disease, anti-leukemia therapy may have been administered within the 2-week period as long but the subject should have recovered from the toxic effects of that therapy. Also, intrathecal therapy may be administered within the 2-week period for subjects with CNS disease.

- Patients who have had an allogeneic or autologous hematopoietic stem cell transplant.

- Patients must have discontinued all growth factors, except Procrit (epoetin), at

least 1 week before study.

- Patients with known HIV positive status or AIDS.

- Patients with known active Hepatitis B, Hepatitis C or cirrhosis.

- History of severe coronary artery disease, including myocardial infarction within the

previous 3 months, arrhythmias other than atrial flutter or fibrillation requiring medication, or uncontrolled congestive heart failure.

- Patients with active uncontrolled infection, fever of infection, or evidence for

progressive disease by CT scans of the lungs, sinuses, or abdomen. Patients who are on antimicrobial therapy and stable, CT scans must have been stable for 4 weeks, may be enrolled but there must be no evidence of an active infection. Patients with fever due to leukemia may be enrolled.

- Pregnant or lactating patients. Female patients of childbearing potential must have

a negative serum pregnancy test within 14 days before study entry.

Locations and Contacts

Southern Alberta Children's Cancer Program, Calgary, Alberta T3B6A8, Canada

Phoenix Children's Hospital, Phoenix, Arizona 85016-7710, United States

University of Colorado Health Sciences Center and The Children's Hospital, Aurora, Colorado 80045, United States

Pediatrix Hematology/Oncology University of Florida College of Medicine, Gainesville, Florida 32610-0296, United States

Children's Healthcare of Atlanta, Atlanta, Georgia 30322, United States

Vanderbilt Children's Hospital, Nashville, Tennessee 37232-6310, United States

M.D. Anderson Comprehensive Cancer Center, Houston, Texas 77030, United States

Additional Information

Starting date: September 2007
Last updated: September 21, 2010

Page last updated: August 23, 2015

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