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A Study of Pomalidomide (CC-4047) Monotherapy for Children and Young Adults With Recurrent or Progressive Primary Brain Tumors

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ClinicalTrials.gov Identifier: NCT03257631
Recruitment Status : Recruiting
First Posted : August 22, 2017
Last Update Posted : December 4, 2018
Sponsor:
Information provided by (Responsible Party):
Celgene

Brief Summary:

A Phase 2 study that will assess the efficacy, safety and tolerability of pomalidomide in children and young adults aged 1 to < 21 years with recurrent or progressive primary brain tumors.

The study will consist of 4 parallel groups, one for each of the following primary brain tumor types: high-grade glioma, medulloblastoma, ependymoma and DIPG. A Simon's Optimal two-stage study design will be applied to each group.


Condition or disease Intervention/treatment Phase
Central Nervous System Neoplasms Medulloblastoma Drug: Pomalidomide Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Detailed Description:

This is a Phase 2 multi-center, open-label, parallel-group study that will assess the efficacy, safety and tolerability of pomalidomide in children and young adults aged 1 to < 21 years with recurrent or progressive primary brain tumors after at least one prior standard therapy.

The study will consist of 4 parallel groups, one for each of the following primary brain tumor types: high-grade glioma, medulloblastoma, ependymoma and DIPG. A Simon's Optimal two-stage study design will be applied to each group and enrollment will occur as follows:

  • Stage 1: Nine subjects will be enrolled.
  • Stage 2: If during Stage 1, ≥ 2 subjects achieves either an objective response (either CR or PR) within the first 6 cycles of treatment (within first 3 cycles for DIPG), or a long-term SD, an additional 11 subjects shall be enrolled; otherwise no additional subjects will be enrolled into that group.
  • If a total of 5 or more subjects across all 20 subjects in a given group (Stage 1 and 2) evaluable for the primary endpoint are observed as having either an objective response (either CR or PR) within the first 6 cycles of treatment (within first 3 cycles for DIPG) or a long-term SD, pomalidomide will be considered effective in that disease indication. Subjects who do not meet the criteria for an objective response or disease progression by the end of Cycle 6 (end of Cycle 3 for DIPG subjects) will be considered as having long-term SD.

Response evaluations will be based on MRI results obtained at each site and will be assessed both locally and by an independent central reviewer. Corticosteroid use and clinical assessments (ie, neurologic status) will also be considered when determining overall response.

Tumor assessments will be conducted by standard MRI with and without contrast using three MRI sequences (T1-weighted pre- and post-contrast, T2-weighted, fluid-attenuated inversion recovery [FLAIR]). Overall radiographic objective response will be assessed utilizing the sequence(s) best representative of tumor in the opinion of the neuroradiologist.

Once treatment has been discontinued, subjects will be followed up for up to 5 years from enrollment of the last subject.

Subjects who withdraw from either stage for reasons other than disease progression prior to completing Cycle 1 of study treatment will be replaced.

An independent Data Monitoring Committee will monitor the study conduct.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A PHASE 2 CLINICAL STUDY OF POMALIDOMIDE (CC-4047) MONOTHERAPY FOR CHILDREN AND YOUNG ADULTS WITH RECURRENT OR PROGRESSIVE PRIMARY BRAIN TUMORS
Actual Study Start Date : August 22, 2017
Estimated Primary Completion Date : March 11, 2019
Estimated Study Completion Date : March 18, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Brain Tumors

Arm Intervention/treatment
Experimental: Pomalidomide
Pomalidomide will administered at a starting dose of 2.6 m2/day. Pomalidomide will be provided as either a capsule (0.5 mg, 1 mg, 2 mg, 3 mg or 4 mg) or as an oral suspension (2 mg/mL).
Drug: Pomalidomide
: Subjects will be administered pomalidomide on Days 1 to 21, followed by a 7-day rest period, of each 28-day treatment cycle and will continue treatment for up to 24 cycles or until disease progression, withdrawal of consent/assent or unresolved toxicities as described in the protocol.
Other Name: CC-4047




Primary Outcome Measures :
  1. Objective Response (OR), Long-term Stable Disease (SD) Rate (ORSDR) [ Time Frame: Up to approximately 6 months ]
    The total number of subjects achieving either an OR (CR or PR) or long-term SD, analyzed per stratum


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Up to approximately 5 years ]
    Total number of subjects achieving an OR (either CR or PR) analyzed per stratum

  2. Long-term stable disease rate [ Time Frame: Up to approximately 6 months ]
    Total number of subjects achieving a long-term SD analyzed per stratum

  3. Duration of response [ Time Frame: Up to approximately 5 years ]
    The time from first achievement of CR or PR under study treatment, whichever occurs first, until first documentation of progressive disease (PD) or death of any cause

  4. Progression-free survival [ Time Frame: Up to approximately 5 years ]
    The time from enrollment until first documentation of PD and/or death of any cause

  5. Overall Survival [ Time Frame: Up to approximately 5 years ]
    The time from enrollment until death of any cause

  6. Adverse Events (AEs) [ Time Frame: Up to approximately 5 years ]
    Type, frequency, and severity of AEs and relationship to study drug



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:

  1. Subject is 1 to < 21 years of age at the time of signing the Informed Consent Form/Informed Assent Form (ICF/IAF).
  2. Subject (when applicable, parental/legal representative) must understand and voluntarily sign an ICF/IAF prior to any study-related assessments/procedures being conducted.
  3. Subject has received at least one prior standard therapy (or generally accepted upfront therapy if no standard exists) and have no known curative therapy.
  4. Subject has a diagnosis of high-grade glioma, medulloblastoma, ependymoma or Diffuse intrinsic pontine glioma (DIPG) that is recurrent or progressive. Subjects with neurofibromatosis type 1 (NF-1) associated tumors are eligible if the meet all other eligibility criteria.
  5. Subject has histological verification of tumor either at the time of diagnosis or recurrence. Subjects with DIPG are exempt from histologic verification if they have typical Magnetic resonance imaging (MRI) findings of DIPG
  6. Subject has measurable disease defined as a tumor that is measurable in 2 perpendicular diameters on MRI. For a lesion to be considered measurable, it must be at least twice the slice thickness on MRI (ie, visible on 2 or more axial slices)
  7. To document the degree of tumor at study baseline, the following scan(s) must be obtained:

    • A brain MRI with and without contrast (ie, gadolinium) and a spine MRI with contrast within 21 days prior to first dose of study treatment. For subjects on steroids, baseline MRI scans must be performed while on stable or decreasing dose of steroids for at least 5 days.

  8. Subject has Karnofsky (age ≥ 16 years) or Lansky (age < 16 years) performance status score ≥ 50 at screening
  9. Subject has adequate bone marrow function defined as:

    • Peripheral Absolute neutrophil count (ANC) ≥ 1000/mm33
    • Platelet count ≥ 100,000/mm3 (transfusion independent defined as no platelet transfusion within 7 days and recovery from nadir)
    • Hemoglobin ≥ 8 g/dL (red blood cell [RBC] transfusion is allowed)
  10. Subject has adequate renal function defined as:

    Adequate real function with Sserum creatinine based on age/gender calculated using the Schwartz formula as described in protocol, or a 24-hour creatinine clearance or radioisotope glomerular filtration rate (GFR) (radioisotope or iothalamate) ≥ 70 mL/min/1.73 m2.

  11. Subject has adequate liver function defined as:

    • Total bilirubin ≤ 1.5 X upper limit of normal (ULN) for current age (≤ 3 X ULN if increase in bilirubin is attributable to Gilbert's Syndrome)
    • Alanine aminotransferase (ALT) (SPGT) is ≤ 3 X ULN for age
    • Serum albumin ≥ 3 g/dL
  12. Subject has adequate pulmonary function defined as:

    • No evidence of dyspnea at rest
    • A pulse oximetry ≥ 93%
  13. Subject has recovered from clinically significant acute treatment related toxicities from all prior therapies. Recovery is defined as a toxicity Grade ≤ 2 (common terminology criteria for adverse events [CTCAE] v. 4.03).
  14. Subject has no significant worsening in clinical status for a minimum of 7 days prior to first dose of study drug.
  15. Subject (and when applicable, with parental/legal representative) is willing and able to adhere to the study visit schedule and other protocol requirements.
  16. Females of Childbearing Potential (FCBP) and male subjects who have reached puberty (and when applicable, with parental/legal representative) must agree to undergo physician-approved reproductive education and discuss the side effects of the study therapy on reproduction.
  17. Females of childbearing potential must agree and meet the following conditions below: to

    • Medically supervised (ie, performed in a clinic) pregnancy testing, including those who commit to true abstinence. Two pregnancy tests must be conducted prior to starting pomalidomide. The first pregnancy test must be performed 10 to 14 days prior to the start of pomalidomide and the second pregnancy test must be performed within 24 hours prior to starting pomalidomide. Females of childbearing potential with regular or no menstrual cycles must also agree to have pregnancy tests weekly for the first 28 days study participation, every 28 days while on study, at study treatment discontinuation, and at Day 28 following pomalidomide discontinuation. If menstrual cycles are irregular, the pregnancy testing must occur weekly for the first 28 days of study participation and then every 14 days while on study, at study treatment discontinuation visit, and at Days 14 and 28 following pomalidomide discontinuation.
    • Female subjects must, as appropriate to age and at the discretion of the study Investigator, either commit to true abstinence from heterosexual contact and/or agree to the use of two reliable forms of approved and effective contraceptive methods simultaneously. The two methods of reliable contraception must include one highly effective method (ie, oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; vasectomized partner) and one additional effective barrier method (ie, male condom, diaphragm, cervical cap) 28 days prior to starting pomalidomide, throughout the entire duration of study treatment including dose interruptions and 28 days after discontinuation of pomalidomide.
    • All male and female subjects must follow all requirements defined in the pomalidomide Pregnancy Prevention Program.
  18. Male subjects must, as appropriate to age and the discretion of the study physician:

    • Practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of child bearing potential while participating in the study, during dose interruptions and for at least 28 days following pomalidomide discontinuation, even if he has undergone a successful vasectomy or practices complete abstinence.

Exclusion Criteria:

  1. Subject has a history of non-central line related thrombosis (arterial or venous), more than one prior central-line related thrombosis or known coagulopathy.
  2. Subject has first degree family member with a known hereditary coagulopathy.
  3. Subject is actively on anticoagulation therapy.
  4. Subject has had major (per Investigator discretion) surgery, with the exception of tumor resection, within 21 days from first dose of study drug.
  5. Subject has previously received (presence of any of the following will exclude a subject from enrollment):

    • Any prior treatment with pomalidomide. Subjects who have prior treatment with other immunomodulatory compounds (thalidomide, lenalidomide) ARE eligible if they meet all other eligibility criteria and did not have allergic reactions or other "significant toxicity" per Investigator discretion associated with lenalidomide or thalidomide use.
    • Myelosuppressive chemotherapy, immunotherapy, or any investigational agent: ≤ 21 days (≤ 42 days if a nitrosourea) prior to screening.
    • Biological (anti-neoplastic) therapy: ≤ 7 days prior to screening.
    • Immunomodulatory therapy: ≤ 28 days prior to screening.
    • Monoclonal antibody treatment and agents with known prolonged half-lives: < 3 halflives have elapsed or ≤ 28 days prior to screening, whichever is longer.
    • Prior radiation:

    Cranial irradiation, total body irradiation (TBI), or ≥ 50% radiation of pelvis ≤ 3 months prior to screening.

    Focal irradiation: ≤ 3 weeks prior to screening if radiation field involved a nontarget lesion; ≤ 6 weeks prior to screening if radiation field involved a target lesion. Note: True disease progression following prior irradiation therapy must be confirmed by Investigator prior to screening.

    • Bone marrow transplant: < 6 months since allogeneic bone marrow transplant prior to screening. < 3 months since autologous bone marrow/stem cell transplant prior to screening.

    < 3 months since stem cell transplant (SCT) or Rescue without TBI with no evidence of GVHD prior to screening.

    • Radioisotopes: fluorothymidine (18FLT) ≤ 72 hours prior to first dose of study drug

  6. Subject has received therapy with a known moderate to potent CYP1A2 inhibitor within 14 days or 5 half-lives of first dose of study treatment (whichever is longer).
  7. Subject has received colony-stimulating growth factor(s) within 7 days prior to screening (or within 14 days if subject received polyethylene glycol formulations).
  8. Subject is pregnant, breast-feeding or lactating.
  9. Subject has an untreated or uncontrolled infection defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment.
  10. Subject has active infectious hepatitis, type A, B, or C, or chronic carriers of hepatitis C.
  11. Subject has any prior history of malignancies, other than high-grade glioma, medulloblastoma, ependymoma or DIPG (Note: radiation-associated gliomas are excluded from enrollment)
  12. Subject who, in the opinion of the Investigator, has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
  13. Subject has any condition including the presence of laboratory abnormalities which, in the opinion of the Investigator, places the subject at unacceptable risk if he/she were to participate in the study.
  14. Subject has any condition that confounds the ability to interpret data from the study.
  15. Subject has symptomatic cardiac disorders (CTCAE v. 4.03 Grade 3 and 4)

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): NCT03257631


Contacts
Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com

Locations
United States, California
Stanford University Cancer Center Recruiting
Stanford, California, United States, 94305-5750
United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32611
United States, Illinois
Ann and Robert H Lurie Childrens Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
United States, Maryland
National Cancer Institute Recruiting
Bethesda, Maryland, United States, 20892
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
France
Centre Oscar Lambret Recruiting
Lille, France, 59020
Centre Leon Berard Recruiting
Lyon, France, 69008
Hopital d'Enfants de la Timone Recruiting
Marseille Cedex 01, France, 13005
Institut Curie Recruiting
Paris, France, 75005
Hopital des Enfants Recruiting
Toulouse, France, 31059
CHU Nancy Hematology Recruiting
Vandoeuvre les Nancy, France, 54511
Institut Gustave Roussy Faculte de Medecine Paris Sud Service de pneumologie Recruiting
Villejuif Cedex, France, 94805
Italy
Istituto G. Gaslini Ospedale Pediatrico IRCCS Recruiting
Genova, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori Recruiting
Milan, Italy, 20133
Ospedale Bambin Gesu Recruiting
Roma, Italy, 00165
Spain
Hospital Universitario Vall D Hebron Recruiting
Barcelona, Spain, 8035
Hospital Infantil Universitario Nino Jesus Recruiting
Madrid, Spain, 28009
Hospital Universitario La Fe Recruiting
Valencia, Spain, 46026
United Kingdom
Leeds General Infirmary Recruiting
Leeds, United Kingdom, LS7 4SA
Great Ormond Street Hospital Recruiting
London, United Kingdom, WC1N 3JH
The Royal Marsden Hospital Recruiting
Sutton-Surrey, United Kingdom, SM2 5PT
Sponsors and Collaborators
Celgene
Investigators
Study Director: Bouchra Benettaib, MD Celgene Corporation

Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT03257631     History of Changes
Other Study ID Numbers: CC-4047-BRN-001
U1111-1199-3348 ( Registry Identifier: WHO )
2016-002903-25 ( EudraCT Number )
First Posted: August 22, 2017    Key Record Dates
Last Update Posted: December 4, 2018
Last Verified: December 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Celgene:
Pediatric
Brain Tumor
Central Nervous System Neoplasms
Glioma
High-grade glioma
HGG
Ependymoma
Medulloblastoma
DIPG
Diffuse intrinsic pontine gliomaProgressive
RecurrentPomalidomide
PomalystImnovid
CC-4047
Children

Additional relevant MeSH terms:
Brain Neoplasms
Medulloblastoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neuroectodermal Tumors, Primitive
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Pomalidomide
Thalidomide
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents