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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01553149
• Collaborator: (none)
• Enrollment: 75
• Locations: 126
• Arms: 2
• Patients Per Site: 0.6

Study Details

Study Description

Brief 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 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.

Condition or Disease	Intervention/Treatment	Phase
Neurofibromatosis Type 1; Recurrent Childhood Pilocytic Astrocytoma; Recurrent Childhood Visual Pathway Glioma	Drug: Lenalidomide; Other: Pharmacological Study	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

1. 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.

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

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

4. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 75 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Randomized Trial of Lenalidomide (NSC # 703813) in Pediatric Patients With Recurrent, Refractory or Progressive Juvenile Pilocytic Astrocytomas and Optic Pathway Gliomas
• Actual Study Start Date: Mar 19, 2012
• Actual Primary Completion Date: Jun 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Lenalidomide; Given PO; Other Names: CC-5013 CC5013 CDC 501 Revlimid ; Other: Pharmacological Study; Correlative studies
Experimental: 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.	Drug: Lenalidomide; Given PO; Other Names: CC-5013 CC5013 CDC 501 Revlimid ; Other: Pharmacological Study; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Number of Patients Who Demonstrate Complete or Partial Response [26 cycles of chemotherapy - up to 3 years after enrollment]

   Number of patients who demonstrate a complete or partial response as defined below: Complete Response - Complete disappearance of all known disease for at least 4 weeks; Partial Response - A reduction of at least 50% in the size of all measurable tumor as quantitated by the sum of the products of the largest diameters of measurable lesions when compared with that measurement at the time of study enrollment and maintained for at least 4 weeks.

2. Number of Patients Who Demonstrate Early Progression [Up to 180 days after enrollment]

   Number of patients with disease progression during the first six months of protocol therapy. Disease progression is defined as ≥ 25% increase in the sum of the products of the largest diameters of the measurable lesions or the appearance of one or more new lesions when compared with the measurements of lesions at the time of enrollment.

Secondary Outcome Measures

1. Event-free Survival [EFS] [Up to 3 years after study enrollment]

   Estimated 3-year EFS where EFS is calculated as the time from study enrollment to disease progression, disease relapse, occurrence of a second malignant neoplasm, death from any cause or last follow-up whichever occurs first. Kaplan-Meier method is used for estimation. Patients without an event are censored at last contact.

2. Overall Survival [OS] [Up to 3 years after study enrollment]

   Estimated 3-year overall survival is calculated as the time from study enrollment to death from any cause or last follow-up whichever occurs first. Kaplan-Meier method is used for estimation. Patients alive at last contact are censored at that time.

3. Number of Patients With Toxic Events After 2 Dose Reductions [While receiving protocol therapy up to 3 years after study enrollment]

   Number of patients who have an additional significant toxicity coded using Common Terminology Criteria for Adverse Events Version 5.0 after experiencing two dose reductions from their assigned treatment dose.

4. Pharmacokinetic Parameters of Lenalidomide [Between days 5-21 of course 1 and each dose reduction]

   Concentration of lenalidomide obtained from any day between day 5 and 21 of the first cycle of chemotherapy in nanograms per mL.

5. Magnetic Resonance Imaging Sequence [Up to 3 years]

   Response categories (complete response, partial response, stable disease, and progression) will be determined from the following three standard magnetic resonance sequences, T2-weighted, fluid attenuated inversion recovery, T1-weighted post-contrast. Percent agreement between the sequences will be estimated as the number of follow-up scans in which the corresponding sequence agreed divided by the total number of follow-up scans.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Alabama	Birmingham	Alabama	United States	35233
2	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama	United States	35233
3	Phoenix Childrens Hospital	Phoenix	Arizona	United States	85016
4	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202-3591
5	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
6	Kaiser Permanente Downey Medical Center	Downey	California	United States	90242
7	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
8	Loma Linda University Medical Center	Loma Linda	California	United States	92354
9	Miller Children's and Women's Hospital Long Beach	Long Beach	California	United States	90806
10	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
11	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
12	Valley Children's Hospital	Madera	California	United States	93636
13	Kaiser Permanente-Oakland	Oakland	California	United States	94611
14	Children's Hospital of Orange County	Orange	California	United States	92868
15	Lucile Packard Children's Hospital Stanford University	Palo Alto	California	United States	94304
16	Sutter Medical Center Sacramento	Sacramento	California	United States	95816
17	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
18	UCSF Medical Center-Parnassus	San Francisco	California	United States	94143
19	UCSF Medical Center-Mission Bay	San Francisco	California	United States	94158
20	Children's Hospital Colorado	Aurora	Colorado	United States	80045
21	Connecticut Children's Medical Center	Hartford	Connecticut	United States	06106
22	Alfred I duPont Hospital for Children	Wilmington	Delaware	United States	19803
23	Children's National Medical Center	Washington	District of Columbia	United States	20010
24	Lee Memorial Health System	Fort Myers	Florida	United States	33901
25	Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida	United States	33908
26	University of Florida Health Science Center - Gainesville	Gainesville	Florida	United States	32610
27	Nemours Children's Clinic-Jacksonville	Jacksonville	Florida	United States	32207
28	AdventHealth Orlando	Orlando	Florida	United States	32803
29	Arnold Palmer Hospital for Children	Orlando	Florida	United States	32806
30	Nemours Children's Clinic - Orlando	Orlando	Florida	United States	32806
31	Nemours Children's Hospital	Orlando	Florida	United States	32827
32	Nemours Children's Clinic - Pensacola	Pensacola	Florida	United States	32504
33	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida	United States	33701
34	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia	United States	30322
35	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
36	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
37	Saint Luke's Cancer Institute - Boise	Boise	Idaho	United States	83712
38	Lurie Children's Hospital-Chicago	Chicago	Illinois	United States	60611
39	University of Illinois	Chicago	Illinois	United States	60612
40	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
41	Loyola University Medical Center	Maywood	Illinois	United States	60153
42	Advocate Children's Hospital-Oak Lawn	Oak Lawn	Illinois	United States	60453
43	Saint Jude Midwest Affiliate	Peoria	Illinois	United States	61637
44	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
45	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana	United States	46260
46	Blank Children's Hospital	Des Moines	Iowa	United States	50309
47	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
48	Norton Children's Hospital	Louisville	Kentucky	United States	40202
49	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70112
50	Children's Hospital New Orleans	New Orleans	Louisiana	United States	70118
51	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
52	National Institutes of Health Clinical Center	Bethesda	Maryland	United States	20892
53	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
54	C S Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
55	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
56	Michigan State University Clinical Center	East Lansing	Michigan	United States	48824-7016
57	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
58	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota	United States	55404
59	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905
60	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
61	Columbia Regional	Columbia	Missouri	United States	65201
62	Children's Mercy Hospitals and Clinics	Kansas City	Missouri	United States	64108
63	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri	United States	63104
64	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
65	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
66	Children's Hospital and Medical Center of Omaha	Omaha	Nebraska	United States	68114
67	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada	United States	89135
68	Summerlin Hospital Medical Center	Las Vegas	Nevada	United States	89144
69	Nevada Cancer Research Foundation NCORP	Las Vegas	Nevada	United States	89169
70	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
71	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
72	Morristown Medical Center	Morristown	New Jersey	United States	07960
73	Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital	New Brunswick	New Jersey	United States	08903
74	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
75	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467
76	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
77	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
78	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
79	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
80	New York Medical College	Valhalla	New York	United States	10595
81	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
82	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
83	East Carolina University	Greenville	North Carolina	United States	27834
84	Children's Hospital Medical Center of Akron	Akron	Ohio	United States	44308
85	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
86	Rainbow Babies and Childrens Hospital	Cleveland	Ohio	United States	44106
87	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
88	Dayton Children's Hospital	Dayton	Ohio	United States	45404
89	Mercy Children's Hospital	Toledo	Ohio	United States	43608
90	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
91	Oregon Health and Science University	Portland	Oregon	United States	97239
92	Penn State Children's Hospital	Hershey	Pennsylvania	United States	17033
93	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
94	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
95	Medical University of South Carolina	Charleston	South Carolina	United States	29425
96	Prisma Health Richland Hospital	Columbia	South Carolina	United States	29203
97	BI-LO Charities Children's Cancer Center	Greenville	South Carolina	United States	29605
98	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
99	East Tennessee Childrens Hospital	Knoxville	Tennessee	United States	37916
100	Saint Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
101	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
102	Dell Children's Medical Center of Central Texas	Austin	Texas	United States	78723
103	Driscoll Children's Hospital	Corpus Christi	Texas	United States	78411
104	Medical City Dallas Hospital	Dallas	Texas	United States	75230
105	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
106	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
107	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas	United States	77030
108	Primary Children's Hospital	Salt Lake City	Utah	United States	84113
109	Children's Hospital of The King's Daughters	Norfolk	Virginia	United States	23507
110	Seattle Children's Hospital	Seattle	Washington	United States	98105
111	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington	United States	99204
112	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin	United States	53792
113	Children's Hospital of Wisconsin	Milwaukee	Wisconsin	United States	53226
114	Royal Brisbane and Women's Hospital	Herston	Queensland	Australia	4029
115	Royal Children's Hospital-Brisbane	Herston	Queensland	Australia	4029
116	Queensland Children's Hospital	South Brisbane	Queensland	Australia	4101
117	Royal Children's Hospital	Parkville	Victoria	Australia	3052
118	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6008
119	British Columbia Children's Hospital	Vancouver	British Columbia	Canada	V6H 3V4
120	IWK Health Centre	Halifax	Nova Scotia	Canada	B3K 6R8
121	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8N 3Z5
122	Kingston Health Sciences Centre	Kingston	Ontario	Canada	K7L 2V7
123	The Montreal Children's Hospital of the MUHC	Montreal	Quebec	Canada	H3H 1P3
124	Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec	Canada	H3T 1C5
125	Starship Children's Hospital	Grafton	Auckland	New Zealand	1145
126	Christchurch Hospital	Christchurch		New Zealand	8011

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Katherine E Warren, Children's Oncology Group

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 1, 2018

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01553149
• Other Study ID Numbers: NCI-2012-00703; NCI-2012-00703; s12-02726; COG-ACNS1022; ACNS1022; CDR0000728296; ACNS1022; ACNS1022; U10CA180886; U10CA098543
• First Posted: Mar 14, 2012
• Last Update Posted: Jul 28, 2022
• Last Verified: Jul 1, 2022

• Additional relevant MeSH terms: Glioma; Astrocytoma; Neurofibromatoses; Neurofibromatosis 1; Recurrence; Lenalidomide

Study Results

Participant Flow

Arm/Group Title	Arm I (Low-dose Lenalidomide)	Arm II (High-dose Lenalidomide)
Arm/Group Description	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. Lenalidomide: Given PO Pharmacological Study: Correlative studies	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. Lenalidomide: Given PO Pharmacological Study: Correlative studies
Period Title: Overall Study
STARTED	37	38
COMPLETED	32	18
NOT COMPLETED	5	20

Baseline Characteristics

Arm/Group Title	Arm I (Low-dose Lenalidomide)	Arm II (High-dose Lenalidomide)	Total
Arm/Group Description	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. Lenalidomide: Given PO Pharmacological Study: Correlative studies	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. Lenalidomide: Given PO Pharmacological Study: Correlative studies	Total of all reporting groups
Overall Participants	37	38	75
Age (Count of Participants)
<=18 years	37 100%	38 100%	75 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	8	9	9
Sex: Female, Male (Count of Participants)
Female	17 45.9%	14 36.8%	31 41.3%
Male	20 54.1%	24 63.2%	44 58.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 8.1%	2 5.3%	5 6.7%
Not Hispanic or Latino	32 86.5%	35 92.1%	67 89.3%
Unknown or Not Reported	2 5.4%	1 2.6%	3 4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 2.6%	1 1.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 8.1%	2 5.3%	5 6.7%
White	31 83.8%	31 81.6%	62 82.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	3 8.1%	4 10.5%	7 9.3%
Region of Enrollment (participants) [Number]
United States	29 78.4%	29 76.3%	58 77.3%
Australia	4 10.8%	6 15.8%	10 13.3%
Canada	4 10.8%	2 5.3%	6 8%
New Zealand	0 0%	1 2.6%	1 1.3%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Who Demonstrate Complete or Partial Response
Description	Number of patients who demonstrate a complete or partial response as defined below: Complete Response - Complete disappearance of all known disease for at least 4 weeks; Partial Response - A reduction of at least 50% in the size of all measurable tumor as quantitated by the sum of the products of the largest diameters of measurable lesions when compared with that measurement at the time of study enrollment and maintained for at least 4 weeks.
Time Frame	26 cycles of chemotherapy - up to 3 years after enrollment

Outcome Measure Data

Analysis Population Description

Only eligible patients are considered in the analysis of this outcome measure

Arm/Group Title	Arm I (Low-dose Lenalidomide)	Arm II (High-dose Lenalidomide)
Arm/Group Description	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. Lenalidomide: Given PO Pharmacological Study: Correlative studies	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. Lenalidomide: Given PO Pharmacological Study: Correlative studies
Measure Participants	37	37
Count of Participants [Participants]	4 10.8%	4 10.5%

2. Primary Outcome

Title	Number of Patients Who Demonstrate Early Progression
Description	Number of patients with disease progression during the first six months of protocol therapy. Disease progression is defined as ≥ 25% increase in the sum of the products of the largest diameters of the measurable lesions or the appearance of one or more new lesions when compared with the measurements of lesions at the time of enrollment.
Time Frame	Up to 180 days after enrollment

Outcome Measure Data

Analysis Population Description

Only eligible patients are considered in the analysis of this outcome measure

Arm/Group Title	Arm I (Low-dose Lenalidomide)	Arm II (High-dose Lenalidomide)
Arm/Group Description	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. Lenalidomide: Given PO Pharmacological Study: Correlative studies	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. Lenalidomide: Given PO Pharmacological Study: Correlative studies
Measure Participants	37	37
Count of Participants [Participants]	6 16.2%	4 10.5%

3. Secondary Outcome

Title	Event-free Survival [EFS]
Description	Estimated 3-year EFS where EFS is calculated as the time from study enrollment to disease progression, disease relapse, occurrence of a second malignant neoplasm, death from any cause or last follow-up whichever occurs first. Kaplan-Meier method is used for estimation. Patients without an event are censored at last contact.
Time Frame	Up to 3 years after study enrollment

Outcome Measure Data

Analysis Population Description

Only eligible patients are considered in the analysis of this outcome measure

Arm/Group Title	Arm I (Low-dose Lenalidomide)	Arm II (High-dose Lenalidomide)
Arm/Group Description	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. Lenalidomide: Given PO Pharmacological Study: Correlative studies	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. Lenalidomide: Given PO Pharmacological Study: Correlative studies
Measure Participants	37	37
Number (95% Confidence Interval) [Percent Probability]	37.84	39.41

4. Secondary Outcome

Title	Overall Survival [OS]
Description	Estimated 3-year overall survival is calculated as the time from study enrollment to death from any cause or last follow-up whichever occurs first. Kaplan-Meier method is used for estimation. Patients alive at last contact are censored at that time.
Time Frame	Up to 3 years after study enrollment

Outcome Measure Data

Analysis Population Description

Only eligible patients are considered in the analysis of this outcome measure

Arm/Group Title	Arm I (Low-dose Lenalidomide)	Arm II (High-dose Lenalidomide)
Arm/Group Description	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. Lenalidomide: Given PO Pharmacological Study: Correlative studies	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. Lenalidomide: Given PO Pharmacological Study: Correlative studies
Measure Participants	37	37
Number (95% Confidence Interval) [Percent Probability]	94.59	91.74

5. Secondary Outcome

Title	Number of Patients With Toxic Events After 2 Dose Reductions
Description	Number of patients who have an additional significant toxicity coded using Common Terminology Criteria for Adverse Events Version 5.0 after experiencing two dose reductions from their assigned treatment dose.
Time Frame	While receiving protocol therapy up to 3 years after study enrollment

Outcome Measure Data

Analysis Population Description

Only eligible patients are considered in the analysis of this outcome measure

Arm/Group Title	Arm I (Low-dose Lenalidomide)	Arm II (High-dose Lenalidomide)
Arm/Group Description	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. Lenalidomide: Given PO Pharmacological Study: Correlative studies	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. Lenalidomide: Given PO Pharmacological Study: Correlative studies
Measure Participants	37	37
Count of Participants [Participants]	2 5.4%	16 42.1%

6. Secondary Outcome

Title	Pharmacokinetic Parameters of Lenalidomide
Description	Concentration of lenalidomide obtained from any day between day 5 and 21 of the first cycle of chemotherapy in nanograms per mL.
Time Frame	Between days 5-21 of course 1 and each dose reduction

Outcome Measure Data

Analysis Population Description

Only eligible patients who have lenalidomide concentration measure are considered in the analysis of this secondary outcome measure

Arm/Group Title	Arm I (Low-dose Lenalidomide)	Arm II (High-dose Lenalidomide)
Arm/Group Description	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. Lenalidomide: Given PO Pharmacological Study: Correlative studies	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. Lenalidomide: Given PO Pharmacological Study: Correlative studies
Measure Participants	22	25
Median (Inter-Quartile Range) [nanograms per mL]	15.1	178.8

7. Secondary Outcome

Title	Magnetic Resonance Imaging Sequence
Description	Response categories (complete response, partial response, stable disease, and progression) will be determined from the following three standard magnetic resonance sequences, T2-weighted, fluid attenuated inversion recovery, T1-weighted post-contrast. Percent agreement between the sequences will be estimated as the number of follow-up scans in which the corresponding sequence agreed divided by the total number of follow-up scans.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	AEs and OAEs: Up to 6 months post-treatment planned as 3 years; All-Cause Mortality: up to 5 years
Adverse Event Reporting Description	Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.
Arm/Group Title	Arm I (Low-dose Lenalidomide)		Arm II (High-dose Lenalidomide)
Arm/Group Description	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. Lenalidomide: Given PO Pharmacological Study: Correlative studies		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. Lenalidomide: Given PO Pharmacological Study: Correlative studies
All Cause Mortality
	Arm I (Low-dose Lenalidomide)		Arm II (High-dose Lenalidomide)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/37 (10.8%)		4/37 (10.8%)
Serious Adverse Events
	Arm I (Low-dose Lenalidomide)		Arm II (High-dose Lenalidomide)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/37 (16.2%)		16/37 (43.2%)
Blood and lymphatic system disorders
Thrombotic thrombocytopenic purpura	0/37 (0%)	0	1/37 (2.7%)	1
Endocrine disorders
Adrenal insufficiency	0/37 (0%)	0	1/37 (2.7%)	1
Hypothyroidism	0/37 (0%)	0	1/37 (2.7%)	1
Eye disorders
Blurred vision	1/37 (2.7%)	1	0/37 (0%)	0
Eye pain	0/37 (0%)	0	1/37 (2.7%)	1
Gastrointestinal disorders
Vomiting	0/37 (0%)	0	1/37 (2.7%)	1
General disorders
Chills	0/37 (0%)	0	1/37 (2.7%)	1
Fever	0/37 (0%)	0	1/37 (2.7%)	1
Infections and infestations
Lung infection	0/37 (0%)	0	1/37 (2.7%)	1
Upper respiratory infection	0/37 (0%)	0	1/37 (2.7%)	1
Investigations
Lymphocyte count decreased	0/37 (0%)	0	1/37 (2.7%)	1
Neutrophil count decreased	2/37 (5.4%)	2	5/37 (13.5%)	5
Platelet count decreased	0/37 (0%)	0	1/37 (2.7%)	1
White blood cell decreased	0/37 (0%)	0	1/37 (2.7%)	1
Metabolism and nutrition disorders
Dehydration	1/37 (2.7%)	1	1/37 (2.7%)	1
Hypocalcemia	0/37 (0%)	0	1/37 (2.7%)	1
Hypokalemia	1/37 (2.7%)	1	2/37 (5.4%)	2
Hyponatremia	1/37 (2.7%)	1	0/37 (0%)	0
Nervous system disorders
Amnesia	0/37 (0%)	0	1/37 (2.7%)	1
Dizziness	0/37 (0%)	0	1/37 (2.7%)	1
Dysphasia	0/37 (0%)	0	1/37 (2.7%)	1
Encephalopathy	0/37 (0%)	0	1/37 (2.7%)	1
Headache	0/37 (0%)	0	3/37 (8.1%)	3
Hydrocephalus	4/37 (10.8%)	4	2/37 (5.4%)	2
Lethargy	0/37 (0%)	0	1/37 (2.7%)	1
Nervous system disorders - Other, specify	0/37 (0%)	0	1/37 (2.7%)	1
Paresthesia	0/37 (0%)	0	1/37 (2.7%)	1
Seizure	0/37 (0%)	0	3/37 (8.1%)	3
Somnolence	0/37 (0%)	0	1/37 (2.7%)	1
Psychiatric disorders
Agitation	0/37 (0%)	0	1/37 (2.7%)	1
Confusion	0/37 (0%)	0	1/37 (2.7%)	1
Suicide attempt	0/37 (0%)	0	1/37 (2.7%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	0/37 (0%)	0	1/37 (2.7%)	1
Vascular disorders
Hypotension	0/37 (0%)	0	1/37 (2.7%)	1
Other (Not Including Serious) Adverse Events
	Arm I (Low-dose Lenalidomide)		Arm II (High-dose Lenalidomide)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/37 (40.5%)		30/37 (81.1%)
Blood and lymphatic system disorders
Anemia	0/37 (0%)	0	2/37 (5.4%)	2
Eye disorders
Eye disorders - Other, specify	0/37 (0%)	0	1/37 (2.7%)	1
Optic nerve disorder	0/37 (0%)	0	1/37 (2.7%)	1
Gastrointestinal disorders
Diarrhea	4/37 (10.8%)	4	0/37 (0%)	0
Nausea	1/37 (2.7%)	1	1/37 (2.7%)	1
Vomiting	1/37 (2.7%)	1	0/37 (0%)	0
General disorders
Fatigue	0/37 (0%)	0	4/37 (10.8%)	4
Infections and infestations
Bronchial infection	0/37 (0%)	0	1/37 (2.7%)	1
Enterocolitis infectious	1/37 (2.7%)	1	0/37 (0%)	0
Lung infection	0/37 (0%)	0	3/37 (8.1%)	3
Skin infection	1/37 (2.7%)	1	0/37 (0%)	0
Upper respiratory infection	0/37 (0%)	0	1/37 (2.7%)	1
Wound infection	0/37 (0%)	0	1/37 (2.7%)	1
Injury, poisoning and procedural complications
Fall	0/37 (0%)	0	1/37 (2.7%)	1
Investigations
Activated partial thromboplastin time prolonged	1/37 (2.7%)	1	0/37 (0%)	0
Alanine aminotransferase increased	1/37 (2.7%)	1	3/37 (8.1%)	3
Aspartate aminotransferase increased	0/37 (0%)	0	1/37 (2.7%)	1
Blood bilirubin increased	0/37 (0%)	0	1/37 (2.7%)	1
Lymphocyte count decreased	4/37 (10.8%)	4	4/37 (10.8%)	4
Neutrophil count decreased	9/37 (24.3%)	9	21/37 (56.8%)	21
Platelet count decreased	0/37 (0%)	0	6/37 (16.2%)	6
Weight gain	0/37 (0%)	0	1/37 (2.7%)	1
White blood cell decreased	1/37 (2.7%)	1	11/37 (29.7%)	11
Metabolism and nutrition disorders
Hyperglycemia	0/37 (0%)	0	1/37 (2.7%)	1
Hypermagnesemia	1/37 (2.7%)	1	0/37 (0%)	0
Hypoalbuminemia	0/37 (0%)	0	1/37 (2.7%)	1
Hypocalcemia	0/37 (0%)	0	1/37 (2.7%)	1
Hypokalemia	1/37 (2.7%)	1	2/37 (5.4%)	2
Hyponatremia	0/37 (0%)	0	1/37 (2.7%)	1
Hypophosphatemia	2/37 (5.4%)	2	1/37 (2.7%)	1
Obesity	1/37 (2.7%)	1	0/37 (0%)	0
Nervous system disorders
Headache	1/37 (2.7%)	1	4/37 (10.8%)	4
Seizure	0/37 (0%)	0	1/37 (2.7%)	1
Psychiatric disorders
Personality change	1/37 (2.7%)	1	0/37 (0%)	0
Respiratory, thoracic and mediastinal disorders
Hypoxia	0/37 (0%)	0	1/37 (2.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.