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

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IIBiomarker/Laboratory analysis, TreatmentUnder 22ACNS1022
NCI-2012-00703, CDR0000728296, COG-ACNS1022, NCT01553149

Trial Description

Summary

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 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.

Further Study Information

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.

Eligibility Criteria

Inclusion Criteria:

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

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

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

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)

All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

All patients and/or their parents or legal guardians must sign a written informed consent

No evidence of dyspnea at rest and a pulse oximetry > 94% if there is clinical indication for determination

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

Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)

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 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)

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 a body surface area (BSA) >= 0.4 m^2 at the time of study enrollment

Platelet count >= 100,000/uL (transfusion independent)

Patients must be able to swallow intact capsules

Steroids: patients who are receiving corticosteroids must be on a stable or decreasing dose for at least 1 week prior to baseline MRI

Growth factor(s): must not have received within 2 weeks of entry onto this study

Total bilirubin =< 1.5 x upper limit of normal (ULN) for age

Peripheral absolute neutrophil count (ANC) >= 1,000/uL

Serum albumin >= 2 g/dL

Patients must have histologic verification of malignancy; histologic confirmation for patients with optic pathway gliomas will not be required

Exclusion Criteria:

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

Patients with a significant systemic illness that is not well-controlled in the opinion of the treating physician 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 who have an uncontrolled or untreated infection are not eligible

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

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 who are pregnant are not eligible

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

Patients with a history of thromboembolism unrelated to a central line, or patients with a known predisposition syndrome for thromboembolism are not eligible

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

National Cancer Institute

  • National Cancer Institute
Katherine Elizabeth Warren, Principal Investigator

Trial Sites

U.S.A.

California
Loma Linda

Loma Linda University Medical Center

Albert Kheradpour
Ph: 909-558-3375

Albert Kheradpour
Principal Investigator

Los Angeles

Children's Hospital Los Angeles

Leo Mascarenhas
Ph: 323-361-4110

Leo Mascarenhas
Principal Investigator

Madera

Children's Hospital Central California

Vonda Lee Crouse
Ph: 866-353-5437

Vonda Lee Crouse
Principal Investigator

San Francisco

UCSF Medical Center-Mission Bay

Anuradha Banerjee
Ph: 877-827-3222

Anuradha Banerjee
Principal Investigator

Connecticut
Hartford

Connecticut Children's Medical Center

Michael Scott Isakoff
Ph: 860-545-9981

Michael Scott Isakoff
Principal Investigator

District of Columbia
Washington

Children's National Medical Center

Jeffrey Stuart Dome
Ph: 202-884-2549

Jeffrey Stuart Dome
Principal Investigator

Florida
Fort Myers

Golisano Children's Hospital of Southwest Florida

Emad K. Salman
Ph: 239-343-5333

Emad K. Salman
Principal Investigator

Orlando

Arnold Palmer Hospital for Children

Vincent Ferdinando Giusti
Ph: 321-841-7246
Email: CancerClinicalTrials@orlandohealth.com

Vincent Ferdinando Giusti
Principal Investigator

Idaho
Boise

Saint Luke's Mountain States Tumor Institute

Eugenia Chang
Ph: 800-845-4624

Eugenia Chang
Principal Investigator

Illinois
Chicago

Lurie Children's Hospital-Chicago

Stewart Goldman
Ph: 773-880-4562

Stewart Goldman
Principal Investigator

University of Illinois

Mary Lou Schmidt
Ph: 312-355-3046

Mary Lou Schmidt
Principal Investigator

Maywood

Loyola University Medical Center

Eugene Suh
Ph: 708-226-4357

Eugene Suh
Principal Investigator

Peoria

Saint Jude Midwest Affiliate

Karen Sofia Fernandez
Ph: 309-655-3258

Karen Sofia Fernandez
Principal Investigator

Indiana
Indianapolis

Riley Hospital for Children

Robert J. Fallon
Ph: 888-823-5923
Email: ctsucontact@westat.com

Robert J. Fallon
Principal Investigator

Saint Vincent Hospital and Health Services

Bassem I. Razzouk
Ph: 317-338-2194

Bassem I. Razzouk
Principal Investigator

Louisiana
New Orleans

Children's Hospital New Orleans

Lolie C. Yu
Ph: 504-894-5377

Lolie C. Yu
Principal Investigator

Michigan
Ann Arbor

C S Mott Children's Hospital

Patricia L. Robertson
Ph: 800-865-1125

Patricia L. Robertson
Principal Investigator

Detroit

Wayne State University/Karmanos Cancer Institute

Zhihong Joanne Wang
Ph: 313-576-9363

Zhihong Joanne Wang
Principal Investigator

Minnesota
Rochester

Mayo Clinic

Amulya Anakapalli Nageswara Rao
Ph: 507-538-7623

Amulya Anakapalli Nageswara Rao
Principal Investigator

Missouri
Saint Louis

Cardinal Glennon Children's Medical Center

William Shay Ferguson
Ph: 314-268-4000

William Shay Ferguson
Principal Investigator

Mercy Hospital Saint Louis

Bethany Graham Sleckman
Ph: 913-948-5588

Bethany Graham Sleckman
Principal Investigator

New Jersey
Hackensack

Hackensack University Medical Center

Steven H. Diamond
Ph: 201-996-2879

Steven H. Diamond
Principal Investigator

New York
New York

Laura and Issac Perlmutter Cancer Center at NYU Langone

Jeffrey C. Allen
Ph: 212-263-4434
Email: prmc.coordinator@nyumc.org

Jeffrey C. Allen
Principal Investigator

Oklahoma
Oklahoma City

University of Oklahoma Health Sciences Center

Rene Yvonne McNall-Knapp
Ph: 405-271-4272
Email: julie-traylor@ouhsc.edu

Rene Yvonne McNall-Knapp
Principal Investigator

Oregon
Portland

Oregon Health and Science University

Kellie Jean Nazemi
Ph: 503-494-1080
Email: trials@ohsu.edu

Kellie Jean Nazemi
Principal Investigator

Pennsylvania
Pittsburgh

Children's Hospital of Pittsburgh of UPMC

Regina Irene Jakacki
Ph: 412-692-5573

Regina Irene Jakacki
Principal Investigator

South Carolina
Columbia

Palmetto Health Richland

Ronnie W. Neuberg
Ph: 803-434-3680

Ronnie W. Neuberg
Principal Investigator

South Dakota
Sioux Falls

Sanford USD Medical Center - Sioux Falls

Kayelyn Jean Wagner
Ph: 605-328-1367

Kayelyn Jean Wagner
Principal Investigator

Tennessee
Memphis

St. Jude Children's Research Hospital

Wayne Lee Furman
Ph: 866-278-5833
Email: info@stjude.org

Wayne Lee Furman
Principal Investigator

Texas
Austin

Dell Children's Medical Center of Central Texas

Amy Catherine Fowler
Ph: 214-648-7097

Amy Catherine Fowler
Principal Investigator

Dallas

Medical City Dallas Hospital

Stanton Carl Goldman
Ph: 972-566-5588

Stanton Carl Goldman
Principal Investigator

Fort Worth

Cook Children's Medical Center

Mary Meaghan Petty Granger
Ph: 682-885-2103

Mary Meaghan Petty Granger
Principal Investigator

Houston

Baylor College of Medicine

Jack Meng-Fen Su
Ph: 713-798-1354
Email: burton@bcm.edu

Jack Meng-Fen Su
Principal Investigator

Utah
Salt Lake City

Primary Children's Hospital

Phillip Evan Barnette
Ph: 801-585-5270

Phillip Evan Barnette
Principal Investigator

Virginia
Norfolk

Childrens Hospital-King's Daughters

Eric Jeffrey Lowe
Ph: 757-668-7243

Eric Jeffrey Lowe
Principal Investigator

Washington
Spokane

Providence Sacred Heart Medical Center and Children's Hospital

Judy L. Felgenhauer
Ph: 800-228-6618
Email: HopeBeginsHere@providence.org

Judy L. Felgenhauer
Principal Investigator

Wisconsin
Madison

University of Wisconsin Hospital and Clinics

Kenneth Brian DeSantes
Ph: 608-262-5223

Kenneth Brian DeSantes
Principal Investigator

Australia

Herston

Royal Brisbane and Women's Hospital

Timothy Edward George Hassall
Ph: 888-823-5923
Email: ctsucontact@westat.com

Timothy Edward George Hassall
Principal Investigator

Parkville

Royal Children's Hospital

Francoise Marie Mechinaud
Email: crdo.info@mcri.edu.au

Francoise Marie Mechinaud
Principal Investigator

South Brisbane

Lady Cilento Children's Hospital

Helen Irving
Ph: 888-823-5923
Email: ctsucontact@westat.com

Helen Irving
Principal Investigator

Canada

British Columbia
Vancouver

British Columbia Children's Hospital

Caron Strahlendorf
Ph: 604-875-2345ext6477

Caron Strahlendorf
Principal Investigator

Nova Scotia
Halifax

IWK Health Centre

Conrad Vincent Fernandez
Ph: 902-470-8394

Conrad Vincent Fernandez
Principal Investigator

Ontario
Hamilton

McMaster Children's Hospital at Hamilton Health Sciences

Carol Portwine
Ph: 905-521-2100ext74595

Carol Portwine
Principal Investigator

Kingston

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Mariana Pradier Silva
Ph: 613-544-2630

Mariana Pradier Silva
Principal Investigator

Quebec
Montreal

The Montreal Children's Hospital of the MUHC

Sharon Barbara Abish
Ph: 514-412-4445
Email: info@thechildren.com

Sharon Barbara Abish
Principal Investigator

New Zealand

Christchurch

Christchurch Hospital

Siobhan Frances Cross
Ph: 03 364 0640

Siobhan Frances Cross
Principal Investigator

Grafton

Starship Children's Hospital

Lochie Rodrick Teague
Ph: 0800 728 436

Lochie Rodrick Teague
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01553149

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.