Central Nervous System TumorsPhase 1NCT03050450
Study of Lenalidomide With Vorinostat in Pediatric Patients With High Grade or Progressive CNS Tumors
A Phase 1 study testing 25 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®), 50 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) and 100 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) in people with Central Nervous System Tumors, run by Johns Hopkins All Children's Hospital at 1 site in United States.
Trial summary
Independently, both lenalidomide and vorinostat have shown promising activity in pediatric central nervous system (CNS) tumors. These are both agents that are not typically part of first-line studies, although both agents are of serious interest and are currently in clinical trials for further investigation. Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Central Nervous System Tumors
- What is being tested?
- 25 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®), 50 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) and 100 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Aug 2016to 19 Dec 2018
- Phase
- Phase 1
- 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 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Must have histologically confirmed central nervous system malignancy for which standard curative measures do not exist or are not loner effective
- Must have measurable disease
- may not have received vorinostat and lenalidomide in combination
- At least 3 weeks since prior chemotherapy
- At least 6 weeks from last nitrosurea
- At least 6 weeks from autologous transplant
Show all 25Show fewer
- At least 3 months from bone marrow donor transplant
- At least 3 weeks from focal radiation
- At least 6 weeks from craniospinal radiation
- Must have not received growth factors within 1 week of study entry
- Must be on a stable or decreasing dose of steroids for 1 week prior
- Must not be receiving any chemo, biologic, or radiation therapy
- Must not be receiving enzyme inducing anticonvulsants or valproic acid
- Must not be receiving pro-thrombotic agents
- Karnofsky or Lansky performance status ≥50%
- Life expectancy of greater than 8 weeks
- Patients must have normal organ and marrow function, including
- Absolute neutrophil count ≥1,000/mcL
- Platelets ≥100,000/mcL
- Pulse oximetry >93%
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
- aspartate aminotransferase (AST)(SGOT)/Alanine transaminase (ALT)(SGPT) ≤2.5 × institutional upper limit of normal
- Creatinine within normal institutional limits OR
- Creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
- The effects of vorinostat and lenalidomide on the developing human fetus are unknown. For this reason and because agents used in this trial are known to be teratogenic, women of child-bearing potential must commit to complete abstinence or use TWO methods of birth control (one highly effective (i.e. intrauterine device (IUD), birth control pills, injections, implants, tubal ligation, partner's vasectomy), and one additional method (i.e. male condom, diaphragm, cervical cap) for the duration of study participation and at least 28 days after completion. Females of childbearing potential must agree to ongoing pregnancy testing and counseling every 28 days about pregnancy precautions. If a female has not had a menstrual period in the preceding 24 consecutive months or has had a hysterectomy, the two methods of birth control requirement does not apply. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must agree to use condoms for the duration of study participation, and 28 days after completion.
Who cannot join
- Patient has not recovered from acute toxic effects of all prior therapies
- Patients who are receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat or lenalidomide
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, dyspnea at rest, symptomatic congestive heart failure, history of thromboembolism unrelated to central line, patients with known predisposition syndrome for thromboembolism, patients receiving anticoagulation therapy, unstable angina pectoris, cardiac arrhythmia, patients receiving enzyme inducing anticonvulsants, patients receiving valproic acid, patients receiving antiplatelet agents (aspirin, anti-inflammatory drugs), or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study due to the potential for teratogenic effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is being treated and not resumed until 28 days after completing therapy.
- HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with these agents. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins All Childen's Hospital
St. Petersburg, Florida, 33701
About this study
Official title: A Phase 1 Study of Lenalidomide in Combination With Vorinostat in Pediatric Patients With High Grade or Progressive Central Nervous System Tumors
Independently, both lenalidomide and vorinostat have shown promising activity in pediatric central nervous system (CNS) tumors. These are both agents that are not typically part of first-line studies, although both agents are of serious interest and are currently in clinical trials for further investigation. This study is to evaluate the combination of lenalidomide and vorinostat in high grade or progressive central nervous system tumors in children.
Read the detailed description
Brain tumors are the second most common cause of cancer in pediatrics and the leading cause of cancer death in children. For children with relapsed, refractory, or recurrent brain tumors, new agents in new combinations are needed. This study is a phase I study designed to provide an objective observation of toxicity and establish a maximum tolerated dose of this combination. In addition, this study will observe the response of children with relapsed or refractory central nervous system tumors. Lenalidomide will be dosed orally once daily days 1-21 consecutive days of a 28 day cycle. Vorinostat will be dosed orally once daily days 1-7 and 15-21 of a 28-day cycle.Doses will be escalated according to standard phase 1 dose escalation criteria. In the absence of treatment delays due to adverse event(s), treatment may continue for 24 cycles.
- Conditions
- Central Nervous System Tumors
- Being tested
- 25 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®), 50 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®), 100 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®), 150 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®), 150 mg/m2 Lenalidomide (Revlimid®) and 230 mg/m2 Vorinostat (Zolinza®)
- Medical subject headings
- Central Nervous System Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
25 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®)Drug
Also called Revlimid®, Zolinza®
Drug: Lenalidomide 25 mg/m2 days 1-21 of a 28 days cycle Drug: Vorinostat 180 mg/m2 days 1-7 and 15-21 of a 28 day cycle
50 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®)Drug
Also called Revlimid®, Zolinza®
Drug: Lenalidomide 50 mg/m2 days 1-21 of a 28 days cycle Drug: Vorinostat 180 mg/m2 days 1-7 and 15-21 of a 28 day cycle
100 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®)Drug
Also called Revlimid®, Zolinza®
Drug: Lenalidomide 100 mg/m2 days 1-21 of a 28 days cycle Drug: Vorinostat 180 mg/m2 days 1-7 and 15-21 of a 28 day cycle
150 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®)Drug
Also called Revlimid®, Zolinza®
Drug: Lenalidomide 150 mg/m2 days 1-21 of a 28 days cycle Drug: Vorinostat 180 mg/m2 days 1-7 and 15-21 of a 28 day cycle
150 mg/m2 Lenalidomide (Revlimid®) and 230 mg/m2 Vorinostat (Zolinza®)Drug
Also called Revlimid®, Zolinza®
Drug: Lenalidomide 150 mg/m2 days 1-21 of a 28 days cycle Drug: Vorinostat 230 mg/m2 days 1-7 and 15-21 of a 28 day cycle
| Study group | Role | What they receive |
|---|---|---|
| dose level 1 | Experimental | 25 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) Receives: Drug: 25 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) |
| dose level 2 | Experimental | 50 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) Receives: Drug: 50 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) |
| dose level 3 | Experimental | 100 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) Receives: Drug: 100 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) |
| dose level 4 | Experimental | 150 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) Receives: Drug: 150 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) |
| dose level 5 | Experimental | 150 mg/m2 Lenalidomide (Revlimid®) and 230 mg/m2 Vorinostat (Zolinza®) Receives: Drug: 150 mg/m2 Lenalidomide (Revlimid®) and 230 mg/m2 Vorinostat (Zolinza®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Number of Adverse Events
Collect and grade all of the adverse events to evaluate for safety. This data was collected for the first 2 cycles for each participant.
Measured: Two 28 day cycles
Secondary outcomes (3)
Best Response of Children With Recurrent or Refractory Central Nervous System Tumors
Best response by MRIs per definitions in the protocol (complete response, partial response, stable disease, progressive disease). MRI's were obtained every 2 cycles and the best response was reported.
Measured: Every 2 cycles up to 24 cycles
2 Year Event Free Survival With Children Treated With This Regimen.
2 year actual event free survival with children treated with this protocol.
Measured: 2 year
Number Participants With Hematologic and Non-hematologic Toxicities
Number participants with grades 3 to 5 hematologic and non-hematologic toxicities. All toxicities are for end of cycle 2.
Measured: Two 28 day cycles
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2017
- Study start10 Aug 2016
- Primary completion19 Dec 2018
- Study completion19 Dec 2018
Why it stopped: Lack of feasibility to accrue patients in allotted time.
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 Central Nervous System TumorsStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins All Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stacie Stapleton, MD, Principal investigator, Johns Hopkins All Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03050450
- Sponsor's protocol ID
- ACH-CNS-005
- Status last verified
- Mar 2021
- First submitted
- 30 Aug 2016
- Last updated
- 5 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of Lenalidomide in Combination With Vorinostat in Pediatric Patients With High Grade or Progressive Central Nervous System Tumors
- ClinicalTrials.gov ID
- NCT03050450
- Acronym / sponsor ID
- ACH-CNS-005
- Conditions
- Central Nervous System Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of feasibility to accrue patients in allotted time.
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Johns Hopkins All Children's HospitalUniversity, hospital or other
- Study start
- 10 Aug 2016 (actual)
- Primary completion
- 19 Dec 2018 (actual)
- Study completion
- 19 Dec 2018 (actual)
- First posted
- 13 Feb 2017 (actual)
- Results
- Posted 5 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Independently, both lenalidomide and vorinostat have shown promising activity in pediatric central nervous system (CNS) tumors. These are both agents that are not typically part of first-line studies, although both agents are of serious interest and are currently in clinical trials for further investigation. This study is to evaluate the combination of lenalidomide and vorinostat in high grade or progressive central nervous system tumors in children.
Detailed description
Brain tumors are the second most common cause of cancer in pediatrics and the leading cause of cancer death in children. For children with relapsed, refractory, or recurrent brain tumors, new agents in new combinations are needed. This study is a phase I study designed to provide an objective observation of toxicity and establish a maximum tolerated dose of this combination. In addition, this study will observe the response of children with relapsed or refractory central nervous system tumors. Lenalidomide will be dosed orally once daily days 1-21 consecutive days of a 28 day cycle. Vorinostat will be dosed orally once daily days 1-7 and 15-21 of a 28-day cycle.Doses will be escalated according to standard phase 1 dose escalation criteria. In the absence of treatment delays due to adverse event(s), treatment may continue for 24 cycles.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| dose level 1 | Experimental | Drug: 25 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®)25 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) |
| dose level 2 | Experimental | Drug: 50 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®)50 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) |
| dose level 3 | Experimental | Drug: 100 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®)100 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) |
| dose level 4 | Experimental | Drug: 150 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®)150 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) |
| dose level 5 | Experimental | Drug: 150 mg/m2 Lenalidomide (Revlimid®) and 230 mg/m2 Vorinostat (Zolinza®)150 mg/m2 Lenalidomide (Revlimid®) and 230 mg/m2 Vorinostat (Zolinza®) |
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (25 listed)
- Must have histologically confirmed central nervous system malignancy for which standard curative measures do not exist or are not loner effective
- Must have measurable disease
- may not have received vorinostat and lenalidomide in combination
- At least 3 weeks since prior chemotherapy
- At least 6 weeks from last nitrosurea
Key exclusion criteria (6 listed)
- Patient has not recovered from acute toxic effects of all prior therapies
- Patients who are receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat or lenalidomide
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, dyspnea at rest, symptomatic congestive heart failure, history of thromboembolism unrelated to central line, patients with known predisposition syndrome for thromboembolism, patients receiving anticoagulation therapy, unstable angina pectoris, cardiac arrhythmia, patients receiving enzyme inducing anticonvulsants, patients receiving valproic acid, patients receiving antiplatelet agents (aspirin, anti-inflammatory drugs), or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study due to the potential for teratogenic effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is being treated and not resumed until 28 days after completing therapy.
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 |
|---|---|---|
| 25 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®)Also: Revlimid®, Zolinza®Drug: Lenalidomide 25 mg/m2 days 1-21 of a 28 days cycle Drug: Vorinostat 180 mg/m2 days 1-7 and 15-21 of a 28 day cycle | Drug | dose level 1 |
| 50 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®)Also: Revlimid®, Zolinza®Drug: Lenalidomide 50 mg/m2 days 1-21 of a 28 days cycle Drug: Vorinostat 180 mg/m2 days 1-7 and 15-21 of a 28 day cycle | Drug | dose level 2 |
| 100 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®)Also: Revlimid®, Zolinza®Drug: Lenalidomide 100 mg/m2 days 1-21 of a 28 days cycle Drug: Vorinostat 180 mg/m2 days 1-7 and 15-21 of a 28 day cycle | Drug | dose level 3 |
| 150 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®)Also: Revlimid®, Zolinza®Drug: Lenalidomide 150 mg/m2 days 1-21 of a 28 days cycle Drug: Vorinostat 180 mg/m2 days 1-7 and 15-21 of a 28 day cycle | Drug | dose level 4 |
| 150 mg/m2 Lenalidomide (Revlimid®) and 230 mg/m2 Vorinostat (Zolinza®)Also: Revlimid®, Zolinza®Drug: Lenalidomide 150 mg/m2 days 1-21 of a 28 days cycle Drug: Vorinostat 230 mg/m2 days 1-7 and 15-21 of a 28 day cycle | Drug | dose level 5 |
Primary outcome
Total Number of Adverse Events
Time frame: Two 28 day cycles
Collect and grade all of the adverse events to evaluate for safety. This data was collected for the first 2 cycles for each participant.
3 secondary outcomes
Best Response of Children With Recurrent or Refractory Central Nervous System Tumors
Time frame: Every 2 cycles up to 24 cycles
2 Year Event Free Survival With Children Treated With This Regimen.
Time frame: 2 year
Number Participants With Hematologic and Non-hematologic Toxicities
Time frame: Two 28 day cycles
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes
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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.
Stacie Stapleton, MD principal investigator
Johns Hopkins All Children's Hospital
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 25 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®), 50 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) and 100 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) in people with Central Nervous System Tumors, run by Johns Hopkins All Children's Hospital 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 25 inclusion and 6 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 5 Apr 2021. 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?
Yes. Results are posted in the registry (first posted 5 Apr 2021). 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?
Total Number of Adverse Events (time frame: Two 28 day cycles). 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 5 Apr 2021.