Study of Lenalidomide With Vorinostat in Pediatric Patients With High Grade or Progressive CNS Tumors

March 8, 2021 updated by: Johns Hopkins All Children's Hospital

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
8

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Saint Petersburg, Florida, United States, 33701
        • Johns Hopkins All Childen's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 year to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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
  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: dose level 1
25 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®)
Drug: 25 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (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
Other Names:
  • Revlimid®
  • Zolinza®
Experimental: dose level 2
50 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®)
Drug: 50 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (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
Other Names:
  • Revlimid®
  • Zolinza®
Experimental: dose level 3
100 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®)
Drug: 100 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (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
Other Names:
  • Revlimid®
  • Zolinza®
Experimental: dose level 4
150 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®)
Drug: 150 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (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
Other Names:
  • Revlimid®
  • Zolinza®
Experimental: dose level 5
150 mg/m2 Lenalidomide (Revlimid®) and 230 mg/m2 Vorinostat (Zolinza®)
Drug: 150 mg/m2 Lenalidomide (Revlimid®) and 230 mg/m2 Vorinostat (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
Other Names:
  • Revlimid®
  • Zolinza®

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Two 28 day cycles

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Best Response of Children With Recurrent or Refractory Central Nervous System Tumors
Time Frame: Every 2 cycles up to 24 cycles
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.
Every 2 cycles up to 24 cycles
2 Year Event Free Survival With Children Treated With This Regimen.
Time Frame: 2 year
2 year actual event free survival with children treated with this protocol.
2 year
Number Participants With Hematologic and Non-hematologic Toxicities
Time Frame: Two 28 day cycles
Number participants with grades 3 to 5 hematologic and non-hematologic toxicities. All toxicities are for end of cycle 2.
Two 28 day cycles

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Johns Hopkins All Children's Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Stacie Stapleton, MD, Johns Hopkins All Children's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 10, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 19, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 19, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 30, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 8, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 13, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 5, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 8, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ACH-CNS-005

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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