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

NCT03050450 | Terminated Phase 1 Results DMC

• 1 other identifier: ACH-CNS-005
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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. This study is to evaluate the combination of lenalidomide and vorinostat in high grade or progressive central nervous system tumors in children.

Conditions

Central Nervous System Tumors

Outcome Measures

Primary Outcomes (1)

• 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.

  Two 28 day cycles

Secondary Outcomes (3)

• Best Response of Children With Recurrent or Refractory Central Nervous System Tumors

  Every 2 cycles up to 24 cycles

• 2 Year Event Free Survival With Children Treated With This Regimen.

  2 year

• Number Participants With Hematologic and Non-hematologic Toxicities

  Two 28 day cycles

Study Arms (5)

dose level 1

EXPERIMENTAL

25 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®)

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®)

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®)

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®)

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®)

Drug: 150 mg/m2 Lenalidomide (Revlimid®) and 230 mg/m2 Vorinostat (Zolinza®)

Interventions

25 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) DRUG

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

Also known as: Revlimid®, Zolinza®

dose level 1

50 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) DRUG

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

Also known as: Revlimid®, Zolinza®

dose level 2

100 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) DRUG

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

Also known as: Revlimid®, Zolinza®

dose level 3

150 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) DRUG

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

Also known as: Revlimid®, Zolinza®

dose level 4

150 mg/m2 Lenalidomide (Revlimid®) and 230 mg/m2 Vorinostat (Zolinza®) DRUG

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

Also known as: Revlimid®, Zolinza®

dose level 5

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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%

You may not qualify if:

• 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.

Sponsors & Collaborators

• Johns Hopkins All Children's Hospital: lead

Study Sites (1)

Johns Hopkins All Childen's Hospital

St. Petersburg, Florida, 33701, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms

Interventions

Lenalidomide; Vorinostat

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids

Results Point of Contact

• Title: Dr Stacie Stapleton
• Organization: Johns Hopkins All Children's Hospital (St. Petersburg, FL)

stacie.stapleton@jhmi.edu

17274701017

Study Officials

• Stacie Stapleton, MD

  Johns Hopkins All Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2016
• First Posted: February 13, 2017
• Study Start: August 10, 2016
• Primary Completion: December 19, 2018
• Study Completion: December 19, 2018
• Last Updated: April 5, 2021
• Results First Posted: April 5, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)