Imetelstat Sodium in Treating Younger Patients With Recurrent or Refractory Brain Tumors

• Sponsor: Pediatric Brain Tumor Consortium (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01836549
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 43
• Locations: 11
• Arm: 1
• Duration (Months): 37
• Patients Per Site: 3.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This molecular biology and phase II trial studies how well imetelstat sodium works in treating younger patients with recurrent or refractory brain tumors. Imetelstat sodium may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Condition or Disease	Intervention/Treatment	Phase
Anaplastic Astrocytoma; Anaplastic Ependymoma; Astrocytoma, Grade II; Ependymoma; Giant Cell Glioblastoma; Glioblastoma; Gliosarcoma; Oligodendroglioma; Brainstem Tumors	Drug: imetelstat sodium	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

• Molecular Biology:

1. To test the ability of imetelstat (GRN163L) to inhibit telomerase activity by Telomere Repeat Amplification Protocol (TRAP) in tumor and peripheral blood mononuclear cells (PBMNCs) of children with recurrent or refractory HGG or ependymoma.

1. To characterize the pharmacokinetics of imetelstat in plasma, cerebrospinal fluid (CSF), and tumor tissue of children with recurrent or refractory HGG or ependymoma.

• Phase II:

1. To estimate the sustained objective response rates (complete response (CR) plus partial response (PR), sustained for at least 6 weeks) to imetelstat administered intravenously on Days 1 and 8 of a 21-day course at the recommended Phase II pediatric dose, 285mg/m2, in children with recurrent or refractory HGG, ependymoma or DIPG. Independent estimates of the objective response rates will be made for each of the three strata, two of which are histologically defined.

SECONDARY OBJECTIVES:

• Phase II only:

1. To assess evidence of telomerase expression by detection of hTERT mRNA and TERC RNA levels by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and telomerase activity by TRAP in archival tumor tissue (for HGG, and ependymoma strata) and to explore association of telomerase positivity with objective response and progression-free survival (PFS).

1. To estimate the stratum-specific PFS distributions of children with recurrent or refractory HGG, ependymoma or DIPG treated with imetelstat.

• Molecular Biology and Phase II:

1. To characterize the plasma and CSF pharmacokinetics of imetelstat in children with recurrent or refractory HGG, ependymoma or DIPG.

1. To assess evidence of telomerase expression by detection of hTERT mRNA and TERC RNA levels by qRT-PCR, telomerase activity by TRAP, and telomere length by telomere terminal restriction fragment (TRF) analysis in PBMNCs prior to treatment with imetelstat and to assess evidence of telomerase inhibition by TRAP and telomere shortening by TRF analysis serially on treatment with imetelstat.

2. To compare incidence of Alternative Lengthening of Telomeres (ALT) mechanism in pediatric HGG, or ependymoma as determined by four different assays 1) ATRX/DAXX nuclear localization by immunofluorescence (IF) assay; 2) telomere-specific signal by fluorescence in situ hybridization (FISH); 3) telomeric terminal restriction fragment (TRF) analysis by Southern blot; and 4) by C circle assay and to assess correlation of these methods for ALT detection.

3. To assess whether ALT status is associated with objective response rates for children with recurrent or refractory HGG, or ependymoma treated with imetelstat.

4. To describe MRI characteristics and diffusion changes of recurrent or refractory HGG, ependymoma and DIPG tumors prior to and after treatment with imetelstat to assess for an early diffusion indicator of response.

5. To measure telomere length of tumors in children with recurrent or refractory HGG, or ependymoma and to assess association of tumor length with tumor response to imetelstat treatment.

6. To assess hTERT promoter mutations and methylation, H3F3A, ATRX, and DAXX mutations, and examine the effects of these modifications in children with recurrent brain tumors using targeted gene, exome, RNA sequencing and methylation arrays of targeted genomic regions.

OUTLINE:

Molecular Biology Phase: Patients will receive one infusion of imetelstat prior to surgery. Surgery will take place 12-24 hours after the infusion of imetelstat. Patients will continue to receive therapy on the same schedule as the Phase II patients starting 14-21 days after surgery.

Phase II: Patients receive imetelstat sodium IV over 2 hours on days 1 and 8. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 43 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Molecular Biology and Phase II Study of Imetelstat (GRN163L) in Children With Recurrent High-Grade Glioma, Ependymoma and Diffuse Intrinsic Pontine Glioma
• Study Start Date: Mar 1, 2013
• Actual Primary Completion Date: Apr 1, 2016
• Actual Study Completion Date: Apr 1, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (imetelstat sodium) Molecular Biology Phase: Patients will receive one infusion of imetelstat prior to surgery. Surgery will take place 12-24 hours after the infusion of imetelstat. Patients will continue to receive therapy on the same schedule as the Phase II patients starting 14-21 days after surgery. Phase II: Patients receive imetelstat sodium IV over 2 hours on days 1 and 8. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Drug: imetelstat sodium; Given IV; Other Names: GRN163L telomerase inhibitor GRN163L

Outcome Measures

Primary Outcome Measures

1. Numver of Patients With Telomerase-positive Archival Tumors Who Demonstrate at Least 50% Reduction [Up to 30 days]

   This outcome measure is for the Molecular biology study only. The assessment was done to identify cases with at least 50% reduction in telomerase activity.

2. Phase II: Stratum-specific Objective Response (CR+PR) Rate [6 months]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=50% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR sustained for at least 6 weeks. For each stratum separately exact confidence interval estimates will be provided for the true, unknown rates of objective response. Estimated by cumulative incidence functions.

Secondary Outcome Measures

1. Number of Participants With Telomerase Inhibition [Up to 30 days]

   This outcome measure is applicable only for the Molecular biology study arm. Telomerase inhibition was assessed in PBMCs and summarised as 'yes-inhibited' vs. 'no inhibition'

2. Stratum-specific Progression-free Survival (PFS) (Phase II) [Up to 2 years, from the date of initial treatment to the earliest date of disease progression, second malignancy or death for subjects who fail; and to the date of last contact for subjects who remain at risk for failure, assessed up to 3 years]

   Kaplan-Meier estimates of distributions of survival and PFS for all eligible subjects who received at least one dose of imetelstat will be provided separately.

3. Number of Patients With Telomerase Expression Data by Detection of hTERT mRNA and TERC RNA Levels by qRT-PCR and Telomerase Activity by TRAP in Archival Tumor Tissue and to Explore Association of Telomerase Positivity With Objective Response and PFS [Up to 30 days. Due to small number of patients evaluable for this objective, we can only provide number of patients with the targetted markers as no analysis with PFS is possible.]

   This secondary objective is for Stratum-B and C only, which enroll HGG and ependymoma patients. We will describe the evidence of telomerase expression by detection of hTERT mRNA and TERC RNA levels by qRT-PCR and telomerase activity by TRAP in archival tumor tissue; Association of telomerase positivity with objective response and PFS will not be able to be conducted as the study was terminated early and there was no objective response.

4. Quantitative MRI Parameters of Tumors Prior to and After Treatment With Imetelstat (Molecular Biology and Phase II Studies) [Up to 30 days]

   This outcome measure was for both Molecular biology and Phase II studies. We will not be able to present the results of this objective as the study was terminated early.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Months to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

INCLUSION CRITERIA:

• MOLECULAR BIOLOGY STUDY

• Tumor: Histologically confirmed Dx of ependymoma or HGG (such as anaplastic astrocytoma, glioblastoma, gliosarcoma, or anaplastic oligodendroglioma) that is recurrent or refractory to conventional therapy.

• Subjects must have clinical indications for surgical resection and be amenable to receiving imetelstat prior to tumor resection. Subjects who require emergent surgery are not eligible for the Molecular Biology study.

• Subjects must provide, fresh flash frozen tumor samples (target 50 mg tissue; as low as 20 mg is adequate) from the time of diagnosis or previous recurrence for the assessment of tumor telomerase activity by the TRAP assay.

• PHASE II STUDY

• Tumor: Subjects must have recurrent or refractory disease with a histological Dx from either the initial presentation or at the time of recurrence. The requirement for histologic verification is waived for subjects with DIPG (stratum D). The following diagnoses are eligible and will be treated in separate strata (B-D): (B) recurrent or refractory high-grade glioma, (such as anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, anaplastic oligodendroglioma); (C) recurrent or refractory ependymoma; (D) recurrent or refractory DIPG (diagnosis by imaging characteristics acceptable; no histologic confirmation required)

• Slides from either initial Dx or relapse must be available for central pathology review for Strata B-C. Tissue slides must be sent per Section 10.1. If tissue slides are unavailable, the study chair must be notified prior to study enrollment.

• All subjects must have bi-dimensionally measurable disease in the brain and/or spine, defined as at least one lesion that can be accurately measured in at least two planes in order to be eligible for this study. Subjects who are enrolled on the Molecular Biology trial and who have measurable disease after the surgical resection and meet all other eligibility criteria for the Phase II study will be counted towards the accrual of the Phase II study.

• FOR BOTH MOLECULAR BIOLOGY AND PHASE II STUDIES

• Subjects with neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration; a baseline detailed neurological exam should clearly document the neurological status of the subject at the time of registration on the study

• Karnofsky >= 50% for > 16 years of age; Lansky >= 50% for children < 16 years of age documented within 14 days of study registration and within 7 days of the start of study drug administration

• Hemoglobin >= 8 g/dL (may receive blood transfusions)

• Absolute neutrophil count > 1,000/ul

• Platelet count >= 100,000/ul (transfusion independent defined as no platelet transfusions with a 4 week period prior to enrollment)

• Serum bilirubin < 2.0 mg/dL (patients with Gilbert syndrome, serum bilirubin < 3.0 x upper limit of normal [ULN])

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 3 x institutional ULN

• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN

• Alkaline phosphatase < 2.5 x institutional ULN

• Albumin >= 2 g/dL

• Adequate coagulation defined as activated partial thromboplastin time (aPTT) < 1.2 x ULN

• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

• Age 1 to < 2 years: maximum serum creatinine (mg/mL) 0.6 for males and 0.6 for females

• Age 2 to < 6 years: maximum serum creatinine (mg/mL) 0.8 for males and 0.8 for females

• Age 6 to < 10 years: maximum serum creatinine (mg/mL) 1 for males and 1 for females

• Age 10 to < 13 years: maximum serum creatinine (mg/mL) 1.2 for males and 1.2 for females

• Age 13 to < 16 years: maximum serum creatinine (mg/mL) 1.5 for males and 1.4 for females

• Age >= 16 years: maximum serum creatinine (mg/mL) 1.7 for males and 1.4 for females

• The threshold creatinine values were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the Centers for Disease and Control (CDC)

• Subjects on systemic anticoagulants are excluded from this study as the drug can cause minor, transient changes in aPTT

• Female subjects of childbearing potential must not be pregnant or breast-feeding; female subjects of childbearing potential must have a negative serum or urine pregnancy test; (pregnancy test must be repeated within 48 hours prior to the start of therapy)

• Subjects of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study

• Subjects must have recovered from the acute toxicities of all prior therapy before entering this study; for those acute baseline adverse events attributable to prior therapy, recovery is defined as a toxicity grade =< 2, using Common Terminology Criteria for Adverse Events (CTCAE) v.4.0, unless otherwise specified in the Inclusion and Exclusion Criteria

• Subjects must have received their last dose of known myelosuppressive anticancer chemotherapy at least three (3) weeks prior to study registration or at least six (6) weeks if nitrosourea

• Subjects must have received their last dose of investigational or biologic agent

= 7 days prior to study registration; in the event that a subject has received an investigational or biologic agent and has experienced >= grade 2 myelosuppression, then at least three (3) weeks must have elapsed prior to registration; if the investigational or biologic agent has a prolonged half-life (>= 7 days) then at least three (3) weeks must have elapsed prior to registration

• Subjects must have completed at least 3 half-life periods from the last dose of monoclonal antibody prior to registration; Note: A list of half-lives of commonly used monoclonal antibodies is available on the Pediatric Brain Tumor Consortium (PBTC) website under Generic Forms and Templates

• Subjects must have received their last dose of radiation (XRT):

• 2 weeks prior to study registration for local palliative XRT (small volume)

• 3 months prior to study registration for craniospinal XRT

• 6 weeks (wks) prior to study registration for other substantial bone marrow irradiation

• Subject must be >= 3 months since autologous bone marrow/stem cell transplantation prior to registration

• Subjects who are receiving a corticosteroid, such as dexamethasone, must be on a stable or decreasing dosage for at least 1 week prior to registration

• At least 7 days since the completion of therapy with a hematopoietic growth agent (filgrastim, sargramostim, and erythropoietin) and 14 days for long-acting formulations

• Ability to understand and the willingness to sign a written informed consent document

EXCLUSION CRITERIA:

• Subjects must not be receiving any other investigational agents

• Subjects with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to imetelstat

• Known coagulopathy or bleeding diathesis

• Subjects with imaging evidence of CNS hemorrhage on baseline MRI obtained within 14 days prior to study enrollment are not eligible; Note: The presence of small punctate areas consistent with hemorrhage will not exclude subjects from participation

• Use of systemic anticoagulant medications

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active serious infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, cirrhosis or psychiatric illness/social situations that would limit compliance with study requirements

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Childrens Hospital Los Angeles	Los Angeles	California	United States	90027-0700
2	Lucile Packard Children's Hospital at Stanford University Medical Center	Palo Alto	California	United States	94304
3	Children's National Medical Center	Washington	District of Columbia	United States	20010-2970
4	Lurie Children's Hospital- Chicago	Chicago	Illinois	United States	60614
5	NCI - Pediatric Oncology Branch	Bethesda	Maryland	United States	20892
6	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
7	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
8	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229-3039
9	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
10	Saint Jude Children's Research Hospital	Memphis	Tennessee	United States	38105-2794
11	Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital	Houston	Texas	United States	77030-2399

Sponsors and Collaborators

• Pediatric Brain Tumor Consortium
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Maryam Fouladi, Pediatric Brain Tumor Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pediatric Brain Tumor Consortium
• ClinicalTrials.gov Identifier: NCT01836549
• Other Study ID Numbers: PBTC-036; NCI-2013-00482; U01CA081457
• First Posted: Apr 22, 2013
• Last Update Posted: Jul 20, 2018
• Last Verified: Jun 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Glioblastoma; Astrocytoma; Ependymoma; Gliosarcoma; Oligodendroglioma; Brain Stem Neoplasms; Imetelstat; Motesanib diphosphate

Study Results

Participant Flow

Arm/Group Title	Molecular Biology Stratum-A	Molecular Biology Stratum-B	Molecular Biology Stratum-C	Stratum-A	Stratum-B	Stratum-C	Stratum-D
Arm/Group Description	This is the Molecular Biology arm for Medulloblastoma/PNET Patients	This is the Molecular Biology arm for High-Grade Glioma Patients	This is the Molecular Biology arm for Ependymoma Patients	This is the Phase-II stratum for Recurrent or Refractory Medulloblastoma/PNET Patients	This is the Phase-II stratum for Recurrent or refractory high-grade glioma patients	This is the Phase-II stratum for Recurrent or refractory ependymoma patients	This is the Phase-II stratum for Recurrent or refractory diffuse intrinsic pontine gliomas (DIPG) patients
Period Title: Overall Study
STARTED	1	1	1	9	18	4	9
COMPLETED	1	1	0	8	18	4	8
NOT COMPLETED	0	0	1	1	0	0	1

Baseline Characteristics

Arm/Group Title	Molecular Biology Stratum-A	Molecular Biology Stratum-B	Stratum-A	Stratum-B	Stratum-C	Stratum-D	Total
Arm/Group Description	This is the Molecular Biology arm for Medulloblastoma/PNET Patients	This is the Molecular Biology arm for High-Grade Glioma Patients	This is the Phase-II stratum for Recurrent or Refractory Medulloblastoma/PNET Patients	This is the Phase-II stratum for Recurrent or refractory high-grade glioma patients	This is the Phase-II stratum for Recurrent or refractory ependymoma patients	This is the Phase-II stratum for Recurrent or refractory diffuse intrinsic pontine gliomas (DIPG) patients	Total of all reporting groups
Overall Participants	1	1	8	18	4	8	40
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	10.41 (NA)	11.33 (NA)	7.94 (4.31)	11.66 (5.24)	11.51 (3.84)	10.45 (2.14)	10.62 (4.40)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	2 25%	7 38.9%	2 50%	4 50%	15 37.5%
Male	1 100%	1 100%	6 75%	11 61.1%	2 50%	4 50%	25 62.5%

Outcome Measures

1. Primary Outcome

Title	Numver of Patients With Telomerase-positive Archival Tumors Who Demonstrate at Least 50% Reduction
Description	This outcome measure is for the Molecular biology study only. The assessment was done to identify cases with at least 50% reduction in telomerase activity.
Time Frame	Up to 30 days

Outcome Measure Data

Analysis Population Description

This outcome measure is only for the molecular biology study. Telomerase inhibition was assessed and the inhibition level was compared with the baseline level to identify increased inhibition.

Arm/Group Title	Molecular Biology Study
Arm/Group Description	Molecular Biology Phase: Patients will receive one infusion of imetelstat prior to surgery. Surgery will take place 12-24 hours after the infusion of imetelstat. Patients will continue to receive therapy on the same schedule as the Phase II patients starting 14-21 days after surgery. Phase II: Patients receive imetelstat sodium IV over 2 hours on days 1 and 8. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. imetelstat sodium: Given IV
Measure Participants	2
Count of Participants [Participants]	1 100%

2. Primary Outcome

Title	Phase II: Stratum-specific Objective Response (CR+PR) Rate
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=50% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR sustained for at least 6 weeks. For each stratum separately exact confidence interval estimates will be provided for the true, unknown rates of objective response. Estimated by cumulative incidence functions.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

This is the Phase-II study cohort, excluding the molecular study patients.

Arm/Group Title	Stratum-A	Stratum-B	Stratum-C	Stratum-D
Arm/Group Description	This is the Phase-II stratum for Recurrent or Refractory Medulloblastoma/PNET Patients	This is the Phase-II stratum for Recurrent or refractory high-grade glioma patients	This is the Phase-II stratum for Recurrent or refractory ependymoma patients	This is the Phase-II stratum for Recurrent or refractory diffuse intrinsic pontine glioma patients
Measure Participants	8	18	4	8
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

3. Secondary Outcome

Title	Number of Participants With Telomerase Inhibition
Description	This outcome measure is applicable only for the Molecular biology study arm. Telomerase inhibition was assessed in PBMCs and summarised as 'yes-inhibited' vs. 'no inhibition'
Time Frame	Up to 30 days

Outcome Measure Data

Analysis Population Description

Samples from six patients were consequently considered evaluable and were analyzed.

Arm/Group Title	Molecular Biology Study
Arm/Group Description	Molecular Biology Phase: Patients will receive one infusion of imetelstat prior to surgery. Surgery will take place 12-24 hours after the infusion of imetelstat. Patients will continue to receive therapy on the same schedule as the Phase II patients starting 14-21 days after surgery. Phase II: Patients receive imetelstat sodium IV over 2 hours on days 1 and 8. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. imetelstat sodium: Given IV
Measure Participants	6
Count of Participants [Participants]	5 500%

4. Secondary Outcome

Title	Stratum-specific Progression-free Survival (PFS) (Phase II)
Description	Kaplan-Meier estimates of distributions of survival and PFS for all eligible subjects who received at least one dose of imetelstat will be provided separately.
Time Frame	Up to 2 years, from the date of initial treatment to the earliest date of disease progression, second malignancy or death for subjects who fail; and to the date of last contact for subjects who remain at risk for failure, assessed up to 3 years

Outcome Measure Data

Analysis Population Description

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Arm/Group Title	Stratum-A	Stratum-B	Stratum-C	Stratum-D
Arm/Group Description	This is the Phase-II stratum for Recurrent or Refractory Medulloblastoma/PNET Patients	This is the Phase-II stratum for Recurrent or refractory high-grade glioma patients	This is the Phase-II stratum for Recurrent or refractory ependymoma patients	This is the Phase-II stratum for Recurrent or refractory diffuse intrinsic pontine gliomas (DIPG) patients
Measure Participants	8	18	4	8
Mean (Standard Error) [days]	30 (3.06)	54.2 (9.97)	50.3 (16.25)	52.6 (14.50)

5. Secondary Outcome

Title	Number of Patients With Telomerase Expression Data by Detection of hTERT mRNA and TERC RNA Levels by qRT-PCR and Telomerase Activity by TRAP in Archival Tumor Tissue and to Explore Association of Telomerase Positivity With Objective Response and PFS
Description	This secondary objective is for Stratum-B and C only, which enroll HGG and ependymoma patients. We will describe the evidence of telomerase expression by detection of hTERT mRNA and TERC RNA levels by qRT-PCR and telomerase activity by TRAP in archival tumor tissue; Association of telomerase positivity with objective response and PFS will not be able to be conducted as the study was terminated early and there was no objective response.
Time Frame	Up to 30 days. Due to small number of patients evaluable for this objective, we can only provide number of patients with the targetted markers as no analysis with PFS is possible.

Outcome Measure Data

Analysis Population Description

This objective is for STRATUM-C patients only, having only 4 patients with TRAP, TERT and TERC levels measured. Due to small sample and having no objective response, association studies of these markers with Objective Reponse and PFS were not possible. Therefore, we only report the the percentage of cases with at least weak TRAP activity.

Arm/Group Title	Stratum-C
Arm/Group Description	This objective is for HGG and ependymoma patients only.
Measure Participants	4
TRAP	3 300%
TERT	3 300%
TERC	3 300%

6. Secondary Outcome

Title	Quantitative MRI Parameters of Tumors Prior to and After Treatment With Imetelstat (Molecular Biology and Phase II Studies)
Description	This outcome measure was for both Molecular biology and Phase II studies. We will not be able to present the results of this objective as the study was terminated early.
Time Frame	Up to 30 days

Outcome Measure Data

Analysis Population Description

This study has been terminated early and the study team decided not to pursue this aim as the results would be inconclusive due to small sample size. Neither the neuroimaging, nor the biology data are available for these patients.

Arm/Group Title	Treatment (Imetelstat Sodium)
Arm/Group Description	Molecular Biology Phase: Patients will receive one infusion of imetelstat prior to surgery. Surgery will take place 12-24 hours after the infusion of imetelstat. Patients will continue to receive therapy on the same schedule as the Phase II patients starting 14-21 days after surgery. Phase II: Patients receive imetelstat sodium IV over 2 hours on days 1 and 8. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. imetelstat sodium: Given IV
Measure Participants	0

Adverse Events

Time Frame	Up to 2 years, which is the total possible therapy duration.
Adverse Event Reporting Description	The AEs we report were experienced while the participants were on study.
Arm/Group Title	Molecular Study-A		Molecular Study-B		Stratum-A		Stratum-B		Stratum-C		Stratum-D
Arm/Group Description	Molecular Study arm for Recurrent or Refractory Medulloblastoma/PNET Patients		Molecular Study arm for Recurrent or refractory high-grade glioma patients		This is the Phase-II stratum for Recurrent or Refractory Medulloblastoma/PNET Patients		This is the Phase-II stratum for Recurrent or refractory high-grade glioma patients		This is the Phase-II stratum for Recurrent or refractory ependymoma patients		This is the Phase-II stratum for Recurrent or refractory diffuse intrinsic pontine gliomas (DIPG) patients
All Cause Mortality
	Molecular Study-A		Molecular Study-B		Stratum-A		Stratum-B		Stratum-C		Stratum-D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Molecular Study-A		Molecular Study-B		Stratum-A		Stratum-B		Stratum-C		Stratum-D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		0/1 (0%)		3/8 (37.5%)		4/18 (22.2%)		2/4 (50%)		3/8 (37.5%)
Gastrointestinal disorders
Dysphagia	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	0/18 (0%)	0	1/4 (25%)	1	0/8 (0%)	0
General disorders
Fatigue	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	0/18 (0%)	0	0/4 (0%)	0	1/8 (12.5%)	1
Death, NOS	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	1/4 (25%)	1	0/8 (0%)	0
Investigations
Alanine aminotransferase increased	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Aspartate aminotransferase increased	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Platelet count decreased	1/1 (100%)	1	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Metabolism and nutrition disorders
Hyponatremia	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle weakness upper limb	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify[Death due to pr	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	0/18 (0%)	0	0/4 (0%)	0	2/8 (25%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify[Progressive dis	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	0/4 (0%)	0	1/8 (12.5%)	1
Intracranial hemorrhage	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	3/18 (16.7%)	3	0/4 (0%)	0	0/8 (0%)	0
Nervous system disorders
Depressed level of consciousness	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	0/18 (0%)	0	0/4 (0%)	0	1/8 (12.5%)	1
Dysarthria	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	0/18 (0%)	0	1/4 (25%)	1	0/8 (0%)	0
Hydrocephalus	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Hypoglossal nerve disorder	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	0/18 (0%)	0	1/4 (25%)	1	0/8 (0%)	0
Nervous system disorders - Other, specify[Cervical hemorrhage]	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Seizure	1/1 (100%)	1	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Syncope	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Psychiatric disorders
Confusion	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Respiratory, thoracic and mediastinal disorders
Apnea	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	1/8 (12.5%)	1
Aspiration	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	0/18 (0%)	0	0/4 (0%)	0	1/8 (12.5%)	1
Dyspnea	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	0/18 (0%)	0	0/4 (0%)	0	1/8 (12.5%)	1
Respiratory failure	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Respiratory, thoracic and mediastinal disorders - Other, specify[increased secretions requiring freq	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	0/18 (0%)	0	0/4 (0%)	0	1/8 (12.5%)	1
Other (Not Including Serious) Adverse Events
	Molecular Study-A		Molecular Study-B		Stratum-A		Stratum-B		Stratum-C		Stratum-D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		1/1 (100%)		8/8 (100%)		16/18 (88.9%)		4/4 (100%)		8/8 (100%)
Blood and lymphatic system disorders
Anemia	1/1 (100%)	1	0/1 (0%)	0	4/8 (50%)	4	7/18 (38.9%)	7	2/4 (50%)	2	0/8 (0%)	0
Cardiac disorders
Sinus tachycardia	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	0/18 (0%)	0	0/4 (0%)	0	1/8 (12.5%)	1
Eye disorders
Eye disorders - Other, specify[Diplopia]	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Scleral disorder	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	1/8 (12.5%)	1
Constipation	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	1/4 (25%)	1	0/8 (0%)	0
Dental caries	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Diarrhea	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Fecal incontinence	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Nausea	0/1 (0%)	0	0/1 (0%)	0	3/8 (37.5%)	3	2/18 (11.1%)	2	1/4 (25%)	1	2/8 (25%)	2
Vomiting	0/1 (0%)	0	0/1 (0%)	0	2/8 (25%)	2	5/18 (27.8%)	5	1/4 (25%)	1	2/8 (25%)	2
General disorders
Fatigue	0/1 (0%)	0	1/1 (100%)	1	4/8 (50%)	4	4/18 (22.2%)	4	1/4 (25%)	1	3/8 (37.5%)	3
Fever	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	0/18 (0%)	0	1/4 (25%)	1	1/8 (12.5%)	1
Infusion related reaction	0/1 (0%)	0	0/1 (0%)	0	3/8 (37.5%)	3	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Localized edema	0/1 (0%)	0	1/1 (100%)	1	0/8 (0%)	0	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Non-cardiac chest pain	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Pain	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Immune system disorders
Allergic reaction	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Infections and infestations
Papulopustular rash	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Upper respiratory infection	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Investigations
Activated partial thromboplastin time prolonged	1/1 (100%)	1	0/1 (0%)	0	1/8 (12.5%)	1	3/18 (16.7%)	3	0/4 (0%)	0	1/8 (12.5%)	1
Alanine aminotransferase increased	1/1 (100%)	1	1/1 (100%)	1	4/8 (50%)	4	8/18 (44.4%)	8	0/4 (0%)	0	6/8 (75%)	6
Alkaline phosphatase increased	0/1 (0%)	0	1/1 (100%)	1	0/8 (0%)	0	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Aspartate aminotransferase increased	1/1 (100%)	1	1/1 (100%)	1	4/8 (50%)	4	7/18 (38.9%)	7	0/4 (0%)	0	3/8 (37.5%)	3
Blood bilirubin increased	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Hemoglobin increased	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	1/8 (12.5%)	1
Investigations - Other, specify[increased PT]	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Lymphocyte count decreased	1/1 (100%)	1	1/1 (100%)	1	5/8 (62.5%)	5	8/18 (44.4%)	8	0/4 (0%)	0	6/8 (75%)	6
Lymphocyte count increased	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Neutrophil count decreased	1/1 (100%)	1	1/1 (100%)	1	4/8 (50%)	4	9/18 (50%)	9	2/4 (50%)	2	1/8 (12.5%)	1
Platelet count decreased	1/1 (100%)	1	1/1 (100%)	1	8/8 (100%)	8	11/18 (61.1%)	11	1/4 (25%)	1	5/8 (62.5%)	5
Weight loss	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
White blood cell decreased	1/1 (100%)	1	1/1 (100%)	1	3/8 (37.5%)	3	8/18 (44.4%)	8	1/4 (25%)	1	1/8 (12.5%)	1
Metabolism and nutrition disorders
Anorexia	0/1 (0%)	0	0/1 (0%)	0	2/8 (25%)	2	3/18 (16.7%)	3	0/4 (0%)	0	0/8 (0%)	0
Dehydration	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	0/18 (0%)	0	1/4 (25%)	1	0/8 (0%)	0
Hyperkalemia	0/1 (0%)	0	1/1 (100%)	1	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Hypermagnesemia	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	2/18 (11.1%)	2	0/4 (0%)	0	0/8 (0%)	0
Hypernatremia	0/1 (0%)	0	1/1 (100%)	1	0/8 (0%)	0	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Hypoalbuminemia	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	2/18 (11.1%)	2	0/4 (0%)	0	1/8 (12.5%)	1
Hypocalcemia	0/1 (0%)	0	1/1 (100%)	1	3/8 (37.5%)	3	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Hypoglycemia	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Hypokalemia	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	3/8 (37.5%)	3
Hyponatremia	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	0/18 (0%)	0	0/4 (0%)	0	2/8 (25%)	2
Hypophosphatemia	0/1 (0%)	0	1/1 (100%)	1	2/8 (25%)	2	1/18 (5.6%)	1	0/4 (0%)	0	2/8 (25%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Muscle weakness left-sided	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	2/18 (11.1%)	2	0/4 (0%)	0	0/8 (0%)	0
Musculoskeletal and connective tissue disorder - Other, specify[Foot pain]	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Myalgia	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	1/4 (25%)	1	1/8 (12.5%)	1
Nervous system disorders
Abducens nerve disorder	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Ataxia	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	2/18 (11.1%)	2	0/4 (0%)	0	2/8 (25%)	2
Dysarthria	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	1/18 (5.6%)	1	0/4 (0%)	0	2/8 (25%)	2
Dysesthesia	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Dysphasia	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	0/18 (0%)	0	0/4 (0%)	0	2/8 (25%)	2
Facial nerve disorder	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	1/18 (5.6%)	1	1/4 (25%)	1	0/8 (0%)	0
Headache	0/1 (0%)	0	1/1 (100%)	1	3/8 (37.5%)	3	4/18 (22.2%)	4	0/4 (0%)	0	2/8 (25%)	2
Hypoglossal nerve disorder	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	2/18 (11.1%)	2	0/4 (0%)	0	0/8 (0%)	0
Intracranial hemorrhage	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Lethargy	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Nervous system disorders - Other, specify[Inability to tolerate own secretions]	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	0/18 (0%)	0	0/4 (0%)	0	1/8 (12.5%)	1
Paresthesia	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Seizure	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Tremor	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Psychiatric disorders
Agitation	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	1/8 (12.5%)	1
Confusion	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Depression	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Insomnia	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	0/18 (0%)	0	0/4 (0%)	0	1/8 (12.5%)	1
Suicidal ideation	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Renal and urinary disorders
Renal and urinary disorders - Other, specify[Urinary Hesitancy]	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Urinary frequency	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	1/8 (12.5%)	1
Urinary incontinence	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Urinary retention	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Respiratory, thoracic and mediastinal disorders
Bronchospasm	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Dyspnea	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	1/4 (25%)	1	0/8 (0%)	0
Epistaxis	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Pruritus	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Vascular disorders
Flushing	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	1/18 (5.6%)	1	0/4 (0%)	0	0/8 (0%)	0
Hot flashes	0/1 (0%)	0	0/1 (0%)	0	0/8 (0%)	0	0/18 (0%)	0	0/4 (0%)	0	1/8 (12.5%)	1
Hypertension	0/1 (0%)	0	0/1 (0%)	0	1/8 (12.5%)	1	0/18 (0%)	0	0/4 (0%)	0	0/8 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.