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A Phase II Randomized Trial of Lenalidomide (NSC # 703813, IND # 70116) in Pediatric Patients With Recurrent, Refractory or Progressive Juvenile Pilocytic Astrocytomas and Optic Pathway Gliomas

Phase 2
21 Years
Open (Enrolling)
Neurofibromatosis Type 1, Recurrent Childhood Pilocytic Astrocytoma, Recurrent Childhood Visual Pathway Glioma

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Trial Information

A Phase II Randomized Trial of Lenalidomide (NSC # 703813, IND # 70116) in Pediatric Patients With Recurrent, Refractory or Progressive Juvenile Pilocytic Astrocytomas and Optic Pathway Gliomas


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/m²/dose) or Regimen B high-dose (115 mg/m²/dose) lenalidomide.


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

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: This is a multicenter study. 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.

Patients undergo blood sample collection between days 5-21 during course 1 for
pharmacokinetic studies.

After completion of study treatment, patients are followed up for up to 5 years.

Inclusion Criteria:

- 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

- 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

- Patients must have been treated with two or fewer anti-cancer regimens, including
chemotherapy, biologic agents, immunotherapy, vaccines, monoclonal antibodies, or
radiation therapy

- At least one prior treatment regimen must have included carboplatin

- Patients who have received prior radiation therapy for this tumor are eligible

- Patients must have a body surface area (BSA) ≥ 0.4 m² at the time of 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

- Peripheral absolute neutrophil count (ANC) ≥ 1,000/μL

- Platelet count ≥ 100,000/μL (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 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 times upper limit of normal (ULN) for age

- Serum glutamic 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

- Not pregnant or breastfeeding

- 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 (4weeks) 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 not had a menstrual period in the preceding 24
consecutive months or 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 every28 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

- See Disease Characteristics

- Patients must have recovered (to common terminology criteria [CTC] 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

- Must not have received myelosuppressive chemotherapy within 3 weeks of entry
onto this study(6 weeks if prior nitrosourea or mitomycin C)

- 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

- At least 42 days after the completion of any type of immunotherapy, e.g., tumor

- At least 3 half-lives of the antibody after the last dose of a monoclonal

- Patients must have had their last fraction of craniospinal radiotherapy (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

- Study-specific limitations on prior therapy:

- Patients who have received prior thalidomide are eligible if all acute
thalidomide-related toxicity has resolved

- Patients must not have received lenalidomide previously

- Must not have received growth factor(s) within 2 weeks of entry onto this study

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

- Concurrent cancer therapy, including chemotherapy, radiation therapy, immunotherapy,
or biologic therapy, may NOT be administered to patients while on this study

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective response - best response

Outcome Description:

The response rate will be calculated as the ratio of the number of patients who demonstrate response (CR or PR) divided by the number of patients evaluable for response.

Outcome Time Frame:

Up to 5 years

Safety Issue:


Principal Investigator

Katherine Warren

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

March 2012

Completion Date:

Related Keywords:

  • Neurofibromatosis Type 1
  • Recurrent Childhood Pilocytic Astrocytoma
  • Recurrent Childhood Visual Pathway Glioma
  • Astrocytoma
  • Glioma
  • Neurofibromatoses
  • Neurofibromatosis 1
  • Osteitis Fibrosa Cystica
  • Optic Nerve Glioma



Baylor College of Medicine Houston, Texas  77030
Roswell Park Cancer Institute Buffalo, New York  14263
Mayo Clinic Rochester, Minnesota  55905
Children's Hospital of Philadelphia Philadelphia, Pennsylvania  19104
University of Mississippi Medical Center Jackson, Mississippi  39216-4505
Washington University School of Medicine Saint Louis, Missouri  63110
Medical City Dallas Hospital Dallas, Texas  75230
Vanderbilt-Ingram Cancer Center Nashville, Tennessee  37232-6838
Morristown Memorial Hospital Morristown, New Jersey  07962-1956
Dana-Farber Cancer Institute Boston, Massachusetts  02115
University of Arkansas for Medical Sciences Little Rock, Arkansas  72205
Children's Hospital Los Angeles Los Angeles, California  90027-0700
Children's National Medical Center Washington, District of Columbia  20010-2970
All Children's Hospital St. Petersburg, Florida  33701
Saint Jude Midwest Affiliate Peoria, Illinois  61637
Carolinas Medical Center Charlotte, North Carolina  28232-2861
University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma  73104
St. Jude Children's Research Hospital Memphis, Tennessee  38105-2794
Driscoll Children's Hospital Corpus Christi, Texas  78466
Southern California Permanente Medical Group Downey, California  90242
Children's Hospital Central California Madera, California  93638-8762
Kosair Children's Hospital Louisville, Kentucky  40202-3830
Children's Hospital Medical Center of Akron Akron, Ohio  44308
Cincinnati Children's Hospital Medical Center Cincinnati, Ohio  45229-3039
Montefiore Medical Center Bronx, New York  10467-2490
Children's Hospitals and Clinics of Minnesota - Minneapolis Minneapolis, Minnesota  55404
University of New Mexico Cancer Center Albuquerque, New Mexico  87131-5636
Nationwide Children's Hospital Columbus, Ohio  43205-2696
Children's Hospital of Pittsburgh of UPMC Pittsburgh, Pennsylvania  15213
Lee Memorial Health System Fort Myers, Florida  33902
University of Alabama at Birmingham Birmingham, Alabama  35294-3300
Children's Hospital of Alabama Birmingham, Alabama  35233
Connecticut Children's Medical Center Hartford, Connecticut  06106
Nemours Children's Clinic - Pensacola Pensacola, Florida  32504
Wayne State University Detroit, Michigan  48202
BI-LO Charities Children's Cancer Center Greenville, South Carolina  29605
University of Texas Southwestern Medical Center Dallas, Texas  
University of Kentucky Lexington, Kentucky  40536-0098
Oregon Health and Science University Portland, Oregon  97201
Florida Hospital Orlando, Florida  32803
Memorial Health University Medical Center Savannah, Georgia  31404
University of Chicago Comprehensive Cancer Center Chicago, Illinois  60637-1470
Seattle Children's Hospital Seattle, Washington  98105
Childrens Memorial Hospital Chicago, Illinois  60614
University of Hawaii Honolulu, Hawaii  96813
Saint Vincent Hospital and Health Services Indianapolis, Indiana  46260
Michigan State University - Breslin Cancer Center East Lansing, Michigan  48824-1313
Saint John's Mercy Medical Center Saint Louis, Missouri  63141
Nevada Cancer Research Foundation CCOP Las Vegas, Nevada  89106
New York University Langone Medical Center New York, New York  10016
Columbia University Medical Center New York, New York  10032
State University of New York Upstate Medical University Syracuse, New York  13210
University of Illinois Chicago, Illinois  60612
Cook Children's Medical Center Fort Worth, Texas  76104
The Children's Medical Center of Dayton Dayton, Ohio  45404
C S Mott Children's Hospital Ann Arbor, Michigan  48109
Riley Hospital for Children Indianapolis, Indiana  46202
UMDNJ - Robert Wood Johnson University Hospital New Brunswick, New Jersey  08903
Miller Children's Hospital Long Beach, California  90806
Childrens Hospital of Orange County Orange, California  92868-3874
Alfred I duPont Hospital for Children Wilmington, Delaware  19803
Nemours Children's Clinic - Jacksonville Jacksonville, Florida  32207-8426
Nemours Childrens Clinic - Orlando Orlando, Florida  32806
Children's Healthcare of Atlanta - Egleston Atlanta, Georgia  30322
The Childrens Mercy Hospital Kansas City, Missouri  64108
Rainbow Babies and Childrens Hospital Cleveland, Ohio  44106
Penn State Hershey Children's Hospital Hershey, Pennsylvania  17033
Palmetto Health Richland Columbia, South Carolina  29203
Childrens Hospital-King's Daughters Norfolk, Virginia  23507
Mark O Hatfield-Warren Grant Magnuson Clinical Center Bethesda, Maryland  20892
Lucile Packard Children's Hospital Stanford University Palo Alto, California  94304
University of California San Francisco Medical Center-Parnassus San Francisco, California  94143
Raymond Blank Children's Hospital Des Moines, Iowa  50309
Sanford USD Medical Center - Sioux Falls Sioux Falls, South Dakota  57117-5134
Providence Sacred Heart Medical Center and Children's Hospital Spokane, Washington  99204