Diffuse Intrinsic Pontine GliomaPhase 1NCT01222754
Lenalidomide and Radiation Therapy in High Grade Gliomas or Diffuse Intrinsic Pontine Gliomas
A Phase 1 study testing Lenalidomide and XRT, 54-59.4 Gy in people with Diffuse Intrinsic Pontine Glioma and Anaplastic Astrocytoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: Children who are diagnosed with brain tumors known as high grade gliomas or diffuse intrinsic pontine gliomas are generally treated with radiation therapy and chemotherapy. However, these tumors are very difficult to cure, and the tumor frequently begins to grow again even after treatment or surgery. Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Diffuse Intrinsic Pontine Glioma, Anaplastic Astrocytoma, High Grade Glioma
- What is being tested?
- Lenalidomide and XRT, 54-59.4 Gy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Nov 2010to 17 Apr 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
None listed.
Who cannot join
- Patients who have had prior chemotherapy for this tumor.
- Patients with an HGG that was completed resected with good margins.
- Patients with a body surface area (BSA) less than or equal to 0.4 m(2) are excluded because the lowest dose of the medication is 5 mg in capsule form.
- Patients with a known coagulation disorder are excluded. Patients with a first-degree relative with a history of venous thrombosis before age 50 yrs or an arterial thrombosis before age 40 yrs must have the following testing performed prior to enrollment to exclude a heritable disorder. Patients with a suspected disorder will be excluded due to the potential increased risk of thrombosis.
- Patients who have had a thromboembolic event that is not line-related are excluded.
- Patients with any significant medical illnesses that, in the investigator s opinion, cannot be adequately controlled with appropriate therapy, would compromise a patient s ability to tolerate this therapy or result in inability to assess toxicity. This includes, but is not limited to uncontrolled intercurrent illness including ongoing or active infection, cardiac disease, renal impairment or psychiatric illness/social situations that would limit compliance with study requirements.
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- Patients with a history of Toxic Epidermal Necrolysis (TEN) or Stevens-Johnson syndrome are excluded as this has occurred in patients receiving lenalidomide.
- Patients receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to lenalidomide (i.e. thalidomide).
- Patients with known hypersensitivity to anhydrous lactose, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate.
- Pregnant or breast feeding females:
- Pregnant women are excluded from this study because lenalidomide is in a class with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lenalidomide, breastfeeding should be discontinued if the mother is treated with lenalidomide.
- Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with lenalidomide. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
- Patients identified as needing spinal radiation at diagnosis (e.g. spinal metastasis or malignant cells identified on CSF cytology) are excluded due to the increased risk of myelosuppression.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Phase I Trial of Lenalidomide and Radiotherapy in Children With Diffuse Intrinsic Pontine Gliomas and High-grade Gliomas
Background:
- Children who are diagnosed with brain tumors known as high grade gliomas or diffuse intrinsic pontine gliomas are generally treated with radiation therapy and chemotherapy. However, these tumors are very difficult to cure, and the tumor frequently begins to grow again even after treatment or surgery. Researchers are interested in determining whether the anticancer drug lenalidomide, which has been used to treat other aggressive types of cancer, is a safe and effective additional treatment for children who are scheduled to receive radiation therapy to treat high grade gliomas or diffuse intrinsic pontine gliomas.
Read more
Objectives:
- To determine the safety and effectiveness of lenalidomide, in conjunction with radiation therapy, as a treatment for children who have been diagnosed with high grade gliomas or diffuse intrinsic pontine gliomas.
Eligibility:
- Children and adolescents up to 21 years of age who have been diagnosed with high grade gliomas or diffuse intrinsic pontine gliomas and have not had radiotherapy or chemotherapy.
Design:
- Participants will be screened with a medical history, physical examination, blood and urine tests, and imaging studies.
- Participants will have two phases of treatment: a lenalidomide plus radiation phase and a lenalidomide-only phase.
- During the radiation phase, participants will take lenalidomide daily and have 6 weeks of radiation therapy (five treatments per week). After the radiation therapy, participants will stop taking lenalidomide for 2 weeks before continuing to the next phase.
- During the lenalidomide-only phase, participants will take lenalidomide daily for 21 days, followed by 7 days without lenalidomide (28-day cycle of treatment). Participants will have up to 24 cycles of lenalidomide.
- Participants will have frequent blood tests during the first cycle of treatment, and will have imaging studies or other tests as required by the study researchers.
- Treatment will continue until the disease progresses, the participant chooses to leave the study, or the researchers end the study.
Read the detailed description
Background:
Brain tumors are the most common solid neoplasm in childhood and the second most common group of pediatric cancers.
Standard therapeutic options for brain tumors consist of surgical resection, radiation therapy and chemotherapy; yet overall survival rates for malignant brain tumors remain low.
Radiation therapy plays a key role in the treatment of diffuse intrinsic pontine gliomas (DIPG) and high-grade gliomas (HGG), and thalidomide has been shown in an animal model to be a radiosensitizer.
Lenalidomide, a thalidomide analog with antiangiogenic, cytotoxic and immunomodulatory effects, is being evaluated for the treatment of CNS tumors, and has shown tolerability and activity in pediatric studies.
Objectives:
To determine the tolerability and toxicity profile of oral lenalidomide when administered to children with newly diagnosed HGG and DIPG with concurrent radiation at doses up to 116 mg/m(2)/day.
To evaluate long-term tolerability of lenalidomide in children with newly-diagnosed HGG and DIPG.
To evaluate magnetic resonance imaging (MRI) sequences for noninvasive monitoring of metabolic and biologic changes in malignant brain tumors with therapy.
To estimate 6 month and 12 month progression free survival (PFS) and overall survival (OS) in this patient population.
To determine if angiogenic and/or immunomodulatory biomarkers in the blood and urine correlate with toxicity and disease response.
To determine the rate of CNS metastatic disease in patients treated with antiangiogenic chemotherapy.
To determine any correlation of steady state pharmacokinetics of lenalidomide with time to progression, number and type of toxicities, and dose limiting toxicities.
Eligibility:
Children with newly diagnosed HGG or DIPG, less than 22 years of age, no prior chemotherapy or radiation therapy, and performance score greater than or equal to 60%.
Children with HGG must have an inoperable or incompletely resected tumor.
Clinical laboratory tests must be within stated limits.
Design:
There will be two phases to therapy on this study, the Radiation Phase and the Maintenance Phase. The MTD will be determined by tolerability during the Radiation Phase.
Eligible patients will receive radiation therapy five days per week to a prescription dose of 54-59.4 Gy, with concurrent administration of lenalidomide daily in a standard Phase I dose escalation design.
At the conclusion of radiation therapy, there will be a two week break followed by maintenance dosing of lenalidomide for 21 days of a 28 day course, until unacceptable toxicity, disease progression or completion of 24 courses of lenalidomide beyond radiotherapy (unless otherwise approved by PI).
Using a multi-center, standard phase I dose escalation design, the total sample size
and the study duration are expected to be 18 - 30 patients and 5-6 years, respectively.
- Being tested
- Lenalidomide, XRT, 54-59.4 Gy
- Keywords
- Newly Diagnosed, DIPG, Radiation Therapy, CC-5013, XRT, Brain Tumor, Glioma, Pediatrics
- Medical subject headings
- Diffuse Intrinsic Pontine Glioma, Astrocytoma, Glioma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenalidomideDrug
- With radiation therapy five days per week, concurrent doses of lenalidomide daily in a standard Phase I dose escalation design.
- Maintenance dosing of lenalidomide, post-radiation, for 21 days of a 28 day course.
XRT, 54-59.4 GyRadiation
Radiation therapy five days per week to a prescription dose of 54-59.4 Gy, with concurrent administration of lenalidomide
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Radiation with Lenalidomide Receives: Drug: Lenalidomide; Radiation: XRT, 54-59.4 Gy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tolerability
The plasma steady state concentration (and CSF levels if available for other reasons) will be correlated with toxicities (type and incidence), time to progression and response.
Measured: 2 years
Toxicity Profile
We will also estimate the population parameters using nonlinear mixed effects modeling methods (NONMEM)
Measured: 2 years
Secondary outcomes (5)
Evaluate MRI Sequences
Measured: 3 years
Progression-free survival
Measured: 4 years
Overall Survival
Measured: 4 years
Biomarkers & toxicity/disease response correlation
Measured: 3 years
Pharmacokinetics correlation with progression and toxicities
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2010 (estimated)
- Study start23 Nov 2010
- Primary completion17 Apr 2019
- Study completion17 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Diffuse Intrinsic Pontine GliomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- John W Glod, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01222754
- Sponsor's protocol ID
- 100219
- Other IDs
- 10-C-0219
- Status last verified
- Dec 2021
- First submitted
- 15 Oct 2010
- Last updated
- 3 Jan 2022
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Siffert J, Greenleaf M, Mannis R, Allen J. Pediatric brain tumors. Child Adolesc Psychiatr Clin N Am. 1999 Oct;8(4):879-903, x.
PubMed 10553209Finlay JL, Boyett JM, Yates AJ, Wisoff JH, Milstein JM, Geyer JR, Bertolone SJ, McGuire P, Cherlow JM, Tefft M, et al. Randomized phase III trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugs-in-1-day regimen. Childrens Cancer Group. J Clin Oncol. 1995 Jan;13(1):112-23. doi: 10.1200/JCO.1995.13.1.112.
PubMed 7799011Freeman CR, Farmer JP. Pediatric brain stem gliomas: a review. Int J Radiat Oncol Biol Phys. 1998 Jan 15;40(2):265-71. doi: 10.1016/s0360-3016(97)00572-5.
PubMed 9457808
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Lenalidomide and Radiotherapy in Children With Diffuse Intrinsic Pontine Gliomas and High-grade Gliomas
- ClinicalTrials.gov ID
- NCT01222754
- Acronym / sponsor ID
- 100219
- Keywords
- Newly Diagnosed, DIPG, Radiation Therapy, CC-5013, XRT, Brain Tumor, Glioma, Pediatrics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 23 Nov 2010 (actual)
- Primary completion
- 17 Apr 2019 (actual)
- Study completion
- 17 Apr 2019 (actual)
- First posted
- 18 Oct 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Children who are diagnosed with brain tumors known as high grade gliomas or diffuse intrinsic pontine gliomas are generally treated with radiation therapy and chemotherapy. However, these tumors are very difficult to cure, and the tumor frequently begins to grow again even after treatment or surgery. Researchers are interested in determining whether the anticancer drug lenalidomide, which has been used to treat other aggressive types of cancer, is a safe and effective additional treatment for children who are scheduled to receive radiation therapy to treat high grade gliomas or diffuse intrinsic pontine gliomas.
Objectives:
- To determine the safety and effectiveness of lenalidomide, in conjunction with radiation therapy, as a treatment for children who have been diagnosed with high grade gliomas or diffuse intrinsic pontine gliomas.
Eligibility:
- Children and adolescents up to 21 years of age who have been diagnosed with high grade gliomas or diffuse intrinsic pontine gliomas and have not had radiotherapy or chemotherapy.
Design:
- Participants will be screened with a medical history, physical examination, blood and urine tests, and imaging studies.
- Participants will have two phases of treatment: a lenalidomide plus radiation phase and a lenalidomide-only phase.
- During the radiation phase, participants will take lenalidomide daily and have 6 weeks of radiation therapy (five treatments per week). After the radiation therapy, participants will stop taking lenalidomide for 2 weeks before continuing to the next phase.
- During the lenalidomide-only phase, participants will take lenalidomide daily for 21 days, followed by 7 days without lenalidomide (28-day cycle of treatment). Participants will have up to 24 cycles of lenalidomide.
- Participants will have frequent blood tests during the first cycle of treatment, and will have imaging studies or other tests as required by the study researchers.
- Treatment will continue until the disease progresses, the participant chooses to leave the study, or the researchers end the study.
Detailed description
Background:
Brain tumors are the most common solid neoplasm in childhood and the second most common group of pediatric cancers.
Standard therapeutic options for brain tumors consist of surgical resection, radiation therapy and chemotherapy; yet overall survival rates for malignant brain tumors remain low.
Radiation therapy plays a key role in the treatment of diffuse intrinsic pontine gliomas (DIPG) and high-grade gliomas (HGG), and thalidomide has been shown in an animal model to be a radiosensitizer.
Lenalidomide, a thalidomide analog with antiangiogenic, cytotoxic and immunomodulatory effects, is being evaluated for the treatment of CNS tumors, and has shown tolerability and activity in pediatric studies.
Objectives:
To determine the tolerability and toxicity profile of oral lenalidomide when administered to children with newly diagnosed HGG and DIPG with concurrent radiation at doses up to 116 mg/m(2)/day.
To evaluate long-term tolerability of lenalidomide in children with newly-diagnosed HGG and DIPG.
To evaluate magnetic resonance imaging (MRI) sequences for noninvasive monitoring of metabolic and biologic changes in malignant brain tumors with therapy.
To estimate 6 month and 12 month progression free survival (PFS) and overall survival (OS) in this patient population.
To determine if angiogenic and/or immunomodulatory biomarkers in the blood and urine correlate with toxicity and disease response.
To determine the rate of CNS metastatic disease in patients treated with antiangiogenic chemotherapy.
To determine any correlation of steady state pharmacokinetics of lenalidomide with time to progression, number and type of toxicities, and dose limiting toxicities.
Eligibility:
Children with newly diagnosed HGG or DIPG, less than 22 years of age, no prior chemotherapy or radiation therapy, and performance score greater than or equal to 60%.
Children with HGG must have an inoperable or incompletely resected tumor.
Clinical laboratory tests must be within stated limits.
Design:
There will be two phases to therapy on this study, the Radiation Phase and the Maintenance Phase. The MTD will be determined by tolerability during the Radiation Phase.
Eligible patients will receive radiation therapy five days per week to a prescription dose of 54-59.4 Gy, with concurrent administration of lenalidomide daily in a standard Phase I dose escalation design.
At the conclusion of radiation therapy, there will be a two week break followed by maintenance dosing of lenalidomide for 21 days of a 28 day course, until unacceptable toxicity, disease progression or completion of 24 courses of lenalidomide beyond radiotherapy (unless otherwise approved by PI).
Using a multi-center, standard phase I dose escalation design, the total sample size
and the study duration are expected to be 18 - 30 patients and 5-6 years, respectively.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Lenalidomide, Radiation: XRT, 54-59.4 GyRadiation with Lenalidomide |
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (0 listed)
Key exclusion criteria (14 listed)
- Patients who have had prior chemotherapy for this tumor.
- Patients with an HGG that was completed resected with good margins.
- Patients with a body surface area (BSA) less than or equal to 0.4 m(2) are excluded because the lowest dose of the medication is 5 mg in capsule form.
- Patients with a known coagulation disorder are excluded. Patients with a first-degree relative with a history of venous thrombosis before age 50 yrs or an arterial thrombosis before age 40 yrs must have the following testing performed prior to enrollment to exclude a heritable disorder. Patients with a suspected disorder will be excluded due to the potential increased risk of thrombosis.
- Patients who have had a thromboembolic event that is not line-related are excluded.
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 |
|---|---|---|
| Lenalidomide1. With radiation therapy five days per week, concurrent doses of lenalidomide daily in a standard Phase I dose escalation design. 2. Maintenance dosing of lenalidomide, post-radiation, for 21 days of a 28 day course. | Drug | 1 |
| XRT, 54-59.4 GyRadiation therapy five days per week to a prescription dose of 54-59.4 Gy, with concurrent administration of lenalidomide | Radiation | 1 |
Primary outcome
Tolerability
Time frame: 2 years
The plasma steady state concentration (and CSF levels if available for other reasons) will be correlated with toxicities (type and incidence), time to progression and response.
Toxicity Profile
Time frame: 2 years
We will also estimate the population parameters using nonlinear mixed effects modeling methods (NONMEM)
5 secondary outcomes
Evaluate MRI Sequences
Time frame: 3 years
Progression-free survival
Time frame: 4 years
Overall Survival
Time frame: 4 years
Biomarkers & toxicity/disease response correlation
Time frame: 3 years
Pharmacokinetics correlation with progression and toxicities
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2022.
- Background: PubMed 10553209Siffert J, Greenleaf M, Mannis R, Allen J. Pediatric brain tumors. Child Adolesc Psychiatr Clin N Am. 1999 Oct;8(4):879-903, x.
- Background: PubMed 7799011Finlay JL, Boyett JM, Yates AJ, Wisoff JH, Milstein JM, Geyer JR, Bertolone SJ, McGuire P, Cherlow JM, Tefft M, et al. Randomized phase III trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugs-in-1-day regimen. Childrens Cancer Group. J Clin Oncol. 1995 Jan;13(1):112-23. doi: 10.1200/JCO.1995.13.1.112.
- Background: PubMed 9457808Freeman CR, Farmer JP. Pediatric brain stem gliomas: a review. Int J Radiat Oncol Biol Phys. 1998 Jan 15;40(2):265-71. doi: 10.1016/s0360-3016(97)00572-5.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
John W Glod, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lenalidomide and XRT, 54-59.4 Gy in people with Diffuse Intrinsic Pontine Glioma and Anaplastic Astrocytoma, run by National Cancer Institute (NCI) at 1 site 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 0 inclusion and 14 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: finished, as of the sponsor's last update on 3 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Tolerability (time frame: 2 years). 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?
On the ClinicalTrials.gov record for NCT01222754, which also lists 3 linked publications.
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 3 Jan 2022; AzTrials last refreshed its copy on 1 Nov 2026.