Clinical trial NCT00055718: Silymarin (Milk Thistle Extract) in Treating Patients With Acute Lymphoblastic Leukemia Who Are Receiving Chemotherapy
Official title: A Pilot Study of Silymarin During Maintenance Therapy in Children With Acute Lymphoblastic Leukemia (ALL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Drug/Agent Toxicity by Tissue/Organ
Leukemia
Keywords: drug/agent toxicity by tissue/organ
childhood acute lymphoblastic leukemia
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-03-07
Enrollment: 50
Sex: ALL
Minimum age (years): 2
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Effect of silymarin on elevated liver function tests (AST, ALT, total bilirubin, and direct bilirubin) at baseline, day 28, and day 56
Secondary outcomes:
measure: Serum antioxidant capacity as measured by the Oxygen Radical Absorbance Capacity (ORAC) at baseline, day 28, and day 56
measure: Oxidative damage as measured by 8-oxodeoxyguanosine adducts at baseline, day 28, and day 56
Other outcomes:
Locations:
city: Miami
country: United States
facility: Miami Children's Hospital
state: Florida
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center at Columbia University
state: New York
city: Akron
country: United States
facility: Children's Hospital Medical Center of Akron
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
city: Hamilton
country: Canada
facility: McMaster Children's Hospital at Hamilton Health Sciences
state: Ontario
Study officials:
affiliation: Herbert Irving Comprehensive Cancer Center
name: Kara Kelly, MD
role: STUDY_CHAIR
References:
citation: 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.