Silymarin (Milk Thistle Extract) in Treating Patients With Acute Lymphoblastic Leukemia Who Are Receiving Chemotherapy

A Pilot Study of Silymarin During Maintenance Therapy in Children With Acute Lymphoblastic Leukemia (ALL)

RATIONALE: Silymarin (milk thistle extract) is an herb that may be effective in treating liver disorders caused by cancer therapy.

PURPOSE: Randomized phase II trial to study the effectiveness of silymarin in treating patients who have acute lymphoblastic leukemia with chemotherapy-related side effects to the liver.

Study Overview

• Status: Completed
• Conditions: Leukemia; Drug/Agent Toxicity by Tissue/Organ
• Intervention / Treatment: Dietary supplement: silymarin

Detailed Description

OBJECTIVES:

• Determine the effect of silymarin, in terms of liver function tests, in patients with acute lymphoblastic leukemia receiving hepatotoxic chemotherapy.
• Determine the effect of this drug on free and conjugated serum silibinin values in these patients.
• Determine the serum antioxidant capacity by Oxygen Radical Absorbance Capacity in patients treated with this drug.
• Determine the oxidative damage, as determined by 8-oxodeoxyguanosine adducts, in patients treated with this drug.

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral silymarin daily for 28 days.
• Arm II: Patients receive oral placebo as in arm I. Patients are followed at day 56.

PROJECTED ACCRUAL: A total of 50 patients (25 per treatment arm) will be accrued for this study.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster Children's Hospital at Hamilton Health Sciences
• United States
  • Florida
    • Miami, Florida, United States, 33155
      • Miami Children's Hospital
  • New York
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center at Columbia University
  • Ohio
    • Akron, Ohio, United States, 44308-1062
      • Children's Hospital Medical Center of Akron
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Washington
    • Seattle, Washington, United States, 98105-3916
      • Children's Hospital and Regional Medical Center - Seattle

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Diagnosis of acute lymphoblastic leukemia (ALL)

• Currently receiving maintenance or continuation phase chemotherapy for ALL

  • Regimen comprising intrathecal and oral methotrexate; vincristine IV; oral prednisone or dexamethasone; and oral mercaptopurine

• Elevated liver function tests, evidenced by 1 of the following criteria:

  • Bilirubin greater than 1.5 times upper limit of normal (ULN)
  • AST greater than 2.5 times ULN
  • ALT greater than 2.5 times ULN

PATIENT CHARACTERISTICS:

Age

• 2 to 21

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• See Disease Characteristics

Renal

• Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• Not specified

Surgery

• Not specified

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Effect of silymarin on elevated liver function tests (AST, ALT, total bilirubin, and direct bilirubin) at baseline, day 28, and day 56

Secondary Outcome Measures

Outcome Measure
Serum antioxidant capacity as measured by the Oxygen Radical Absorbance Capacity (ORAC) at baseline, day 28, and day 56
Oxidative damage as measured by 8-oxodeoxyguanosine adducts at baseline, day 28, and day 56

Collaborators and Investigators

• Sponsor: Herbert Irving Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Kara Kelly, MD, Herbert Irving Comprehensive Cancer Center

Publications and helpful links

General Publications

• Ladas EJ, Kroll DJ, Oberlies NH, Cheng B, Ndao DH, Rheingold SR, Kelly KM. A randomized, controlled, double-blind, pilot study of milk thistle for the treatment of hepatotoxicity in childhood acute lymphoblastic leukemia (ALL). Cancer. 2010 Jan 15;116(2):506-13. doi: 10.1002/cncr.24723.

Study record dates

Study Major Dates

• Study Start: November 1, 2001
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: March 6, 2003
• First Submitted That Met QC Criteria: March 6, 2003
• First Posted (Estimate): March 7, 2003

Study Record Updates

• Last Update Posted (Estimate): December 18, 2013
• Last Update Submitted That Met QC Criteria: December 17, 2013
• Last Verified: May 1, 2006

More Information

Terms related to this study

• Keywords: drug/agent toxicity by tissue/organ; childhood acute lymphoblastic leukemia
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Drug-Related Side Effects and Adverse Reactions; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Antioxidants; Silymarin
• Other Study ID Numbers: CDR0000270914; CPMC-IRB-14117