Anaplastic AstrocytomaPhase 2NCT01836549
Imetelstat Sodium in Treating Younger Patients With Recurrent or Refractory Brain Tumors
A Phase 2 study testing imetelstat sodium in people with Anaplastic Astrocytoma and Anaplastic Ependymoma, run by Pediatric Brain Tumor Consortium at 11 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 months to 21 years
- Conditions the study is for
- Anaplastic Astrocytoma, Anaplastic Ependymoma, Astrocytoma, Grade II
- What is being tested?
- imetelstat sodium
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 11 sitesUnited States
- Study dates
- Mar 2013to Apr 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 months to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
NCI - Pediatric Oncology Branch
Bethesda, Maryland, 20892
Lurie Children's Hospital- Chicago
Chicago, Illinois, 60614
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229-3039
Duke Comprehensive Cancer Center
Durham, North Carolina, 27710
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
Houston, Texas, 77030-2399
Childrens Hospital Los Angeles
Los Angeles, California, 90027-0700
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105-2794
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Lucile Packard Children's Hospital at Stanford University Medical Center
Palo Alto, California, 94304
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Children's National Medical Center
Washington D.C., District of Columbia, 20010-2970
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- Molecular Biology:
- 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.
II. 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:
- 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:
- 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).
II. 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:
- To characterize the plasma and CSF pharmacokinetics of imetelstat in children with recurrent or refractory HGG, ependymoma or DIPG.
II. 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.
III. 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.
IV. To assess whether ALT status is associated with objective response rates for children with recurrent or refractory HGG, or ependymoma treated with imetelstat.
- 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.
VI. 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.
VII. 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.
- Conditions
- Anaplastic Astrocytoma, Anaplastic Ependymoma, Astrocytoma, Grade II, Ependymoma, Giant Cell Glioblastoma, Glioblastoma
- Being tested
- imetelstat sodium
- Medical subject headings
- Astrocytoma, Ependymoma, Glioblastoma, Gliosarcoma, Oligodendroglioma, Brain Stem Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
imetelstat sodiumDrug
Also called GRN163L, telomerase inhibitor GRN163L
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (imetelstat sodium) | Experimental | 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. Receives: Drug: imetelstat sodium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Numver of Patients With Telomerase-positive Archival Tumors Who Demonstrate at Least 50% Reduction
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.
Measured: Up to 30 days
Phase II: Stratum-specific Objective Response (CR+PR) Rate
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.
Measured: 6 months
Secondary outcomes (4)
Number of Participants With Telomerase Inhibition
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'
Measured: Up to 30 days
Stratum-specific Progression-free Survival (PFS) (Phase II)
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.
Measured: 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
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
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.
Measured: 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.
Quantitative MRI Parameters of Tumors Prior to and After Treatment With Imetelstat (Molecular Biology and Phase II Studies)
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.
Measured: Up to 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2013 (estimated)
- Study startMar 2013
- Primary completionApr 2016
- Study completionApr 2016
Why it stopped: Due to several intracranial hemorrhages and recommendation by the PBTC DSMB.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Anaplastic AstrocytomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pediatric Brain Tumor Consortium
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Maryam Fouladi, Principal investigator, Pediatric Brain Tumor Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01836549
- Sponsor's protocol ID
- PBTC-036
- Other IDs
- NCI-2013-00482, U01CA081457
- Status last verified
- Jun 2018
- First submitted
- 17 Apr 2013
- Last updated
- 20 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: Other PBTC investigators can develop a concept proposal and submit it to the PBTC Scientific Committee for a decision to share data and to what extent to share it.
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01836549
- Acronym / sponsor ID
- PBTC-036
- Conditions
- Anaplastic Astrocytoma, Anaplastic Ependymoma, Astrocytoma, Grade II, Ependymoma, Giant Cell Glioblastoma, Glioblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to several intracranial hemorrhages and recommendation by the PBTC DSMB.
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Pediatric Brain Tumor ConsortiumResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Mar 2013
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 22 Apr 2013 (estimated)
- Results
- Posted 20 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- Molecular Biology:
- 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.
II. 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:
- 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:
- 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).
II. 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:
- To characterize the plasma and CSF pharmacokinetics of imetelstat in children with recurrent or refractory HGG, ependymoma or DIPG.
II. 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.
III. 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.
IV. To assess whether ALT status is associated with objective response rates for children with recurrent or refractory HGG, or ependymoma treated with imetelstat.
- 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.
VI. 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.
VII. 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (imetelstat sodium) | Experimental | Drug: imetelstat sodiumMolecular 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. |
Who may qualify
- Ages
- 12 months to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (43 listed)
- MOLECULAR BIOLOGY STUDY
- PHASE II STUDY
- FOR BOTH MOLECULAR BIOLOGY AND PHASE II STUDIES
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| imetelstat sodiumAlso: GRN163L, telomerase inhibitor GRN163LGiven IV | Drug | Treatment (imetelstat sodium) |
Primary outcome
Numver of Patients With Telomerase-positive Archival Tumors Who Demonstrate at Least 50% Reduction
Time frame: 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.
Phase II: Stratum-specific Objective Response (CR+PR) Rate
Time frame: 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.
4 secondary outcomes
Number of Participants With Telomerase Inhibition
Time frame: Up to 30 days
Stratum-specific Progression-free Survival (PFS) (Phase II)
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
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
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.
Quantitative MRI Parameters of Tumors Prior to and After Treatment With Imetelstat (Molecular Biology and Phase II Studies)
Time frame: Up to 30 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. Other PBTC investigators can develop a concept proposal and submit it to the PBTC Scientific Committee for a decision to share data and to what extent to share it.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maryam Fouladi principal investigator
Pediatric Brain Tumor Consortium
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing imetelstat sodium in people with Anaplastic Astrocytoma and Anaplastic Ependymoma, run by Pediatric Brain Tumor Consortium at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 43 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Numver of Patients With Telomerase-positive Archival Tumors Who Demonstrate at Least 50% Reduction (time frame: Up to 30 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2018.