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

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ClinicalTrials.gov Identifier: NCT03050450
Recruitment Status : Suspended (We are not longer enrolling patients, but the study remains open for data collection and analysis.)
First Posted : February 13, 2017
Last Update Posted : May 17, 2019
Sponsor:
Information provided by (Responsible Party):
Stacie Stapleton, MD, Johns Hopkins All Children's Hospital

Brief Summary:
Independently, both lenalidomide and vorinostat have shown promising activity in pediatric central nervous system 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.

Condition or disease Intervention/treatment Phase
Central Nervous System Tumors Drug: 25 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) Drug: 50 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) Drug: 100 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) Drug: 150 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®) Drug: 150 mg/m2 Lenalidomide (Revlimid®) and 230 mg/m2 Vorinostat (Zolinza®) Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of Lenalidomide in Combination With Vorinostat in Pediatric Patients With High Grade or Progressive Central Nervous System Tumors
Actual Study Start Date : August 10, 2016
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : August 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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®




Primary Outcome Measures :
  1. Collect AEs and SAEs using CTCAE version 4.03 and record changes in lesion measurements per imaging [ Time Frame: 5 years ]
    Evaluate the safety and tolerability (AEs and SAEs) and determine the response (per imaging) of children with recurrent or refractory central nervous system tumor with this combination of Lenalidomide and Vorinostat


Secondary Outcome Measures :
  1. Response per imaging measurements and AEs and SAEs will be compared with historical controls [ Time Frame: 5 years ]
    Compare the response per imaging and toxicity (AEs/SAEs) with historical controls in published studies of patients with the same disease

  2. Survival of participants measured by recurrence, relapse or death [ Time Frame: 5 years ]
    Estimate the survival of children treated with Lenalidomide and Vorinostat using Kaplan Meier estimates

  3. Define maximum tolerated dose based on dose escalation and AE/SAE data [ Time Frame: 5 years ]
    Provide safety and efficacy data to recommend further larger studies



Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
  • AST(SGOT)/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. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03050450


Locations
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United States, Florida
Johns Hopkins All Childen's Hospital
Saint Petersburg, Florida, United States, 33701
Sponsors and Collaborators
Johns Hopkins All Children's Hospital
Investigators
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Principal Investigator: Stacie Stapleton, MD Johns Hopkins All Children's Hospital

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Responsible Party: Stacie Stapleton, MD, Director, Pediatric Neuro-Oncology Program, Johns Hopkins All Children's Hospital
ClinicalTrials.gov Identifier: NCT03050450     History of Changes
Other Study ID Numbers: ACH-CNS-005
First Posted: February 13, 2017    Key Record Dates
Last Update Posted: May 17, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Additional relevant MeSH terms:
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Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Nervous System Diseases
Lenalidomide
Vorinostat
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action