Low-Dose or High-Dose Lenalidomide in Treating Younger Patients With Recurrent, Refractory, or Progressive Pilocytic Astrocytoma or Optic Pathway Glioma

NCT ID: NCT01553149

Last Updated: 2025-01-07

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

PHASE2

Total Enrollment

75 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-07-05

Study Completion Date

2023-12-31

Brief Summary

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This randomized phase II trial studies how well low-dose lenalidomide works compared with high-dose lenalidomide in treating younger patients with juvenile pilocytic astrocytomas or optic nerve pathway gliomas that have come back (recurrent), have not responded to treatment (refractory), or are growing, spreading, or getting worse (progressive). Lenalidomide is classified as an immunomodulatory drug as it boosts the immune system. It has other potential anti-tumor effects, for example, it may stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether low-dose lenalidomide is more or less effective than high-dose lenalidomide in treating patients with juvenile pilocytic astrocytomas or optic nerve pathway gliomas.

Detailed Description

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PRIMARY OBJECTIVES:

I. To determine the objective response rate in children with recurrent, refractory, or progressive juvenile pilocytic astrocytomas and optic pathway gliomas who are treated with Regimen A low-dose (20 mg/m\^2/dose) or Regimen B high-dose (115 mg/m\^2/dose) lenalidomide.

SECONDARY OBJECTIVES:

I. To estimate the event-free survival (EFS) (based on standard two-dimensional tumor measurements, determined by each institution) of children with recurrent, refractory, or progressive juvenile pilocytic astrocytomas and optic pathway gliomas who are treated with lenalidomide.

II. To compare response categories and EFS across the 3 magnetic resonance (MR) sequences (T2-weighted, fluid attenuated inversion recovery \[FLAIR\], T1-weighted post-contrast).

III. To correlate steady-state pharmacokinetics of lenalidomide (1 sample obtained between days 5-21) with objective response and EFS.

IV. To evaluate toxicities of long-term lenalidomide use.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I (Regimen A): Patients receive low-dose lenalidomide orally (PO) once daily (QD) on days 1-21. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.

ARM II (Regimen B): Patients receive high-dose lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up annually for approximately 3 years.

Conditions

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Neurofibromatosis Type 1 Recurrent Childhood Pilocytic Astrocytoma Recurrent Childhood Visual Pathway Glioma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm I (low-dose lenalidomide)

Patients receive low-dose lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Lenalidomide

Intervention Type DRUG

Given PO

Pharmacological Study

Intervention Type OTHER

Correlative studies

Arm II (high-dose lenalidomide)

Patients receive high-dose lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Lenalidomide

Intervention Type DRUG

Given PO

Pharmacological Study

Intervention Type OTHER

Correlative studies

Interventions

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Lenalidomide

Given PO

Intervention Type DRUG

Pharmacological Study

Correlative studies

Intervention Type OTHER

Other Intervention Names

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CC-5013 CC5013 CDC 501 Revlimid

Eligibility Criteria

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Inclusion Criteria

* Patients must have a body surface area (BSA) \>= 0.4 m\^2 at the time of study enrollment
* Patients must have a pilocytic astrocytoma or optic pathway glioma that has relapsed, progressed, or become refractory to conventional therapy; patients with neurofibromatosis (NF-1) are eligible
* Patients must have histologic verification of malignancy; histologic confirmation for patients with optic pathway gliomas will not be required
* Patients must have measurable residual disease, defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI); for a lesion to be considered measurable, it must be at least twice the slice thickness on MRI (i.e. visible on more than one slice)
* To document the degree of residual tumor, the following must be obtained:

* All patients must have a brain MRI with and without contrast (gadolinium) within 1 week prior to study enrollment; for patients on steroids, baseline MRI scans must be performed after at least 1 week at a stable or decreasing dose of steroids
* All patients with a history of spinal or leptomeningeal disease, and those patients with symptoms suspicious of spinal disease, must have a spine MRI with and without contrast (gadolinium) performed within 2 weeks prior to study enrollment
* Patients must have a Lansky or Karnofsky performance status score of \>= 60%; use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* Patients must have been treated with at least one prior treatment regimen that included carboplatin; patients who have received prior radiation therapy for this tumor are eligible
* Patients must have recovered (to Common Toxicity Criteria \[CTC\] version \[v.\]4.0 =\< grade 1 unless indicated below) from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study, with the exception of alopecia, weight changes and grade I or II lymphopenia

* Myelosuppressive chemotherapy: must not have received within 3 weeks of entry onto this study (6 weeks if prior nitrosourea or mitomycin-C)
* Biologic (anti-neoplastic agent): at least 7 days after the last dose of a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
* Immunotherapy: at least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
* Monoclonal antibodies: at least 3 half-lives of the antibody after the last dose of a monoclonal antibody
* Radiation therapy (RT): patients must have had their last fraction of craniospinal RT \>= 6 months prior to study entry and their last fraction of focal RT \>= 4 weeks prior to study entry; if the lesion used for on-study criteria is in the radiation field, there must be evidence of tumor progression after radiation therapy was completed
* Study specific limitations on prior therapy:

* Patients who have received thalidomide are eligible if all acute thalidomide-related toxicity has resolved
* Patients must not have received lenalidomide previously
* Growth factor(s): must not have received within 2 weeks of entry onto this study
* Steroids: patients who are receiving corticosteroids must be on a stable or decreasing dose for at least 1 week prior to baseline MRI
* Peripheral absolute neutrophil count (ANC) \>= 1,000/uL
* Platelet count \>= 100,000/uL (transfusion independent)
* Hemoglobin \>= 8.0 g/dL (may receive red blood cell \[RBC\] transfusions)
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/m\^2 OR a serum creatinine based on age/gender as follows:

* 0.4 mg/dL (1 month to \< 6 months of age)
* 0.5 mg/dL (6 months to \< 1 year of age)
* 0.6 mg/dL (1 to \< 2 years of age)
* 0.8 mg/dL (2 to \< 6 years of age)
* 1.0 mg/dL (6 to 10 years of age)
* 1.2 mg/dL (10 to \< 13 years of age)
* 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to \< 16 years of age)
* 1.7 mg/dL (male) or 1.4 mg/dL (female) (\>= 16 years of age)
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 110 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L
* Serum albumin \>= 2 g/dL
* No evidence of dyspnea at rest and a pulse oximetry \> 94% if there is clinical indication for determination
* Patients must be able to swallow intact capsules
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria

* Female patients who are pregnant are not eligible
* Lactating females are not eligible unless they have agreed not to breastfeed their infants while receiving protocol therapy and for 28 days after the last dose of lenalidomide
* Female patients of childbearing potential are not eligible unless they commit to complete abstinence or have been on 2 methods of birth control, including 1 highly effective method and 1 additional method at the same time (unless committing to complete abstinence of heterosexual intercourse) at least 28 days (4 weeks) prior to study enrollment; sexually active females must also agree to remain on 2 methods of birth control, during treatment (including during dose interruptions), and continuing for at least 28 days after the completion of protocol therapy; examples of methods of contraception are as follows:

* Highly effective methods (must use at least 1):

* Intrauterine device (IUD)
* Hormonal (prescription birth control pills, injections, implants)
* Tubal ligation
* Partner's vasectomy
* Additional effective methods:

* Male condom
* Diaphragm
* Cervical cap The two methods of birth control requirement applies to all sexually active females unless they have undergone a hysterectomy or bilateral oophorectomy
* Female patients of childbearing potential (including those who commit to complete abstinence) are not eligible unless they agree to ongoing pregnancy testing and counseling every 28 days about pregnancy precautions and risks of fetal exposure
* Male patients of child fathering potential are not eligible unless they have agreed to use latex condoms during intercourse with a woman of childbearing potential while receiving treatment and for 28 days thereafter
* Patients with a history of thromboembolism unrelated to a central line, or patients with a known predisposition syndrome for thromboembolism are not eligible
* Patients who have an uncontrolled or untreated infection are not eligible
* Patients with known overt cardiac disease, including but not limited to a history of myocardial infarction, severe or unstable angina, clinically significant peripheral vascular disease, grade 2 or greater heart failure, or serious and inadequately controlled cardiac arrhythmia are not eligible
* Patients with a significant systemic illness that is not well-controlled in the opinion of the treating physician are not eligible
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Katherine E Warren

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

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Children's Hospital of Alabama

Birmingham, Alabama, United States

Site Status

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Site Status

Phoenix Childrens Hospital

Phoenix, Arizona, United States

Site Status

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Kaiser Permanente Downey Medical Center

Downey, California, United States

Site Status

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

Loma Linda University Medical Center

Loma Linda, California, United States

Site Status

Miller Children's and Women's Hospital Long Beach

Long Beach, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status

Valley Children's Hospital

Madera, California, United States

Site Status

Kaiser Permanente-Oakland

Oakland, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, United States

Site Status

Sutter Medical Center Sacramento

Sacramento, California, United States

Site Status

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

UCSF Medical Center-Parnassus

San Francisco, California, United States

Site Status

UCSF Medical Center-Mission Bay

San Francisco, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Site Status

Alfred I duPont Hospital for Children

Wilmington, Delaware, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Lee Memorial Health System

Fort Myers, Florida, United States

Site Status

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, United States

Site Status

University of Florida Health Science Center - Gainesville

Gainesville, Florida, United States

Site Status

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, United States

Site Status

AdventHealth Orlando

Orlando, Florida, United States

Site Status

Arnold Palmer Hospital for Children

Orlando, Florida, United States

Site Status

Nemours Children's Clinic - Orlando

Orlando, Florida, United States

Site Status

Nemours Children's Hospital

Orlando, Florida, United States

Site Status

Nemours Children's Clinic - Pensacola

Pensacola, Florida, United States

Site Status

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, United States

Site Status

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, United States

Site Status

Memorial Health University Medical Center

Savannah, Georgia, United States

Site Status

University of Hawaii Cancer Center

Honolulu, Hawaii, United States

Site Status

Saint Luke's Cancer Institute - Boise

Boise, Idaho, United States

Site Status

Lurie Children's Hospital-Chicago

Chicago, Illinois, United States

Site Status

University of Illinois

Chicago, Illinois, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Advocate Children's Hospital-Oak Lawn

Oak Lawn, Illinois, United States

Site Status

Saint Jude Midwest Affiliate

Peoria, Illinois, United States

Site Status

Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

Ascension Saint Vincent Indianapolis Hospital

Indianapolis, Indiana, United States

Site Status

Blank Children's Hospital

Des Moines, Iowa, United States

Site Status

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

Site Status

Norton Children's Hospital

Louisville, Kentucky, United States

Site Status

Tulane University School of Medicine

New Orleans, Louisiana, United States

Site Status

Children's Hospital New Orleans

New Orleans, Louisiana, United States

Site Status

Ochsner Medical Center Jefferson

New Orleans, Louisiana, United States

Site Status

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Michigan State University Clinical Center

East Lansing, Michigan, United States

Site Status

Helen DeVos Children's Hospital at Spectrum Health

Grand Rapids, Michigan, United States

Site Status

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Columbia Regional

Columbia, Missouri, United States

Site Status

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States

Site Status

Cardinal Glennon Children's Medical Center

St Louis, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Mercy Hospital Saint Louis

St Louis, Missouri, United States

Site Status

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, United States

Site Status

Alliance for Childhood Diseases/Cure 4 the Kids Foundation

Las Vegas, Nevada, United States

Site Status

Summerlin Hospital Medical Center

Las Vegas, Nevada, United States

Site Status

Nevada Cancer Research Foundation NCORP

Las Vegas, Nevada, United States

Site Status

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Morristown Medical Center

Morristown, New Jersey, United States

Site Status

Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

New Brunswick, New Jersey, United States

Site Status

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, United States

Site Status

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

State University of New York Upstate Medical University

Syracuse, New York, United States

Site Status

Montefiore Medical Center - Moses Campus

The Bronx, New York, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status

East Carolina University

Greenville, North Carolina, United States

Site Status

Children's Hospital Medical Center of Akron

Akron, Ohio, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Dayton Children's Hospital

Dayton, Ohio, United States

Site Status

Mercy Children's Hospital

Toledo, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

Penn State Children's Hospital

Hershey, Pennsylvania, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Prisma Health Richland Hospital

Columbia, South Carolina, United States

Site Status

BI-LO Charities Children's Cancer Center

Greenville, South Carolina, United States

Site Status

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, United States

Site Status

East Tennessee Childrens Hospital

Knoxville, Tennessee, United States

Site Status

Saint Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Dell Children's Medical Center of Central Texas

Austin, Texas, United States

Site Status

Driscoll Children's Hospital

Corpus Christi, Texas, United States

Site Status

Medical City Dallas Hospital

Dallas, Texas, United States

Site Status

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Site Status

Cook Children's Medical Center

Fort Worth, Texas, United States

Site Status

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, United States

Site Status

Primary Children's Hospital

Salt Lake City, Utah, United States

Site Status

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, United States

Site Status

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States

Site Status

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Site Status

Royal Children's Hospital-Brisbane

Herston, Queensland, Australia

Site Status

Queensland Children's Hospital

South Brisbane, Queensland, Australia

Site Status

Royal Children's Hospital

Parkville, Victoria, Australia

Site Status

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Site Status

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Site Status

IWK Health Centre

Halifax, Nova Scotia, Canada

Site Status

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, Canada

Site Status

Kingston Health Sciences Centre

Kingston, Ontario, Canada

Site Status

The Montreal Children's Hospital of the MUHC

Montreal, Quebec, Canada

Site Status

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, Canada

Site Status

Starship Children's Hospital

Grafton, Auckland, New Zealand

Site Status

Christchurch Hospital

Christchurch, , New Zealand

Site Status

Countries

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United States Australia Canada New Zealand

References

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Warren KE, Vezina G, Krailo M, Springer L, Buxton A, Peer CJ, Figg WD, William-Hughes C, Kessel S, Fouladi M, Gajjar A, Bowers D. Phase II Randomized Trial of Lenalidomide in Children With Pilocytic Astrocytomas and Optic Pathway Gliomas: A Report From the Children's Oncology Group. J Clin Oncol. 2023 Jun 20;41(18):3374-3383. doi: 10.1200/JCO.22.01777. Epub 2023 May 1.

Reference Type DERIVED
PMID: 37126770 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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NCI-2012-00703

Identifier Type: REGISTRY

Identifier Source: secondary_id

s12-02726

Identifier Type: -

Identifier Source: secondary_id

COG-ACNS1022

Identifier Type: -

Identifier Source: secondary_id

ACNS1022

Identifier Type: -

Identifier Source: secondary_id

CDR0000728296

Identifier Type: -

Identifier Source: secondary_id

ACNS1022

Identifier Type: OTHER

Identifier Source: secondary_id

ACNS1022

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180886

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA098543

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-00703

Identifier Type: -

Identifier Source: org_study_id

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