A Study of Pomalidomide Monotherapy for Children and Young Adults With Recurrent or Progressive Primary Brain Tumors

NCT03257631 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: CC-4047-BRN-001U1111-1199-33482016-002903-25
• Study Type: interventional
• Target: 53
• Locations: 5 countries
• Sites: 22

Brief Summary

This study 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 in one of four primary brain tumor types: high-grade glioma (HGG), medulloblastoma, ependymoma and diffuse intrinsic pontine glioma (DIPG).

Conditions

Central Nervous System Neoplasms; Medulloblastoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With an Objective Response and Long-term Stable Disease

  The percentage of participants who achieved either an objective response, defined as a complete response (CR) or partial response (PR) in the first 6 cycles of treatment (or within 3 cycles for DIPG), or long-term stable disease (SD) defined as SD maintained for ≥ 6 cycles (≥ 3 cycles for DIPG), measured from first dose date. CR: Disappearance of all lesions and no new lesions. PR: A reduction of ≥ 50% in the size of measurable lesions, and/or persistence of non-target lesions with no progression or decrease in size. SD: A decrease of \< 50% or an increase of \< 25% in the size of measurable lesions and no evidence of new lesions, response does not meet the criteria for CR, PR, or progressive disease, and/or the persistence of non-target lesions with no progression or decrease in size. Progressive Disease (PD): ≥ 25% increase in the size of the measurable lesions, or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

  6 months (first 6 cycles) or 3 months (first 3 cycles) for participants in the DIPG group

Secondary Outcomes (6)

• Percentage of Participants Who Achieved an Objective Response (ORR)

  6 months (first 6 cycles) or 3 months (first 3 cycles) for participants in the DIPG group

• Percentage of Participants With Long-term Stable Disease

  6 months (first 6 cycles) or 3 months (first 3 cycles) for participants in the DIPG group

• Duration of Response (DoR)

  From the first dose of pomalidomide to the date of the first documented tumor progression or death due to any cause, whichever occurs first (Up to 71 months)

• Kaplan-Meier Estimate of Progression-Free Survival (PFS)

  From the first dose of pomalidomide to the date of the first documented tumor progression or death due to any cause, whichever occurs first (Up to 71 months)

• Kaplan-Meier Estimate of Overall Survival (OS)

  From the first dose of pomalidomide to the date of death due to any cause (Up to 71 months)

Study Arms (1)

Pomalidomide

EXPERIMENTAL

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

Interventions

Pomalidomide DRUG

: 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.

Also known as: CC-4047

Pomalidomide

Eligibility Criteria

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

You may qualify if:

• Subject is 1 to \< 21 years of age at the time of signing the Informed Consent Form/Informed Assent Form (ICF/IAF).
• Subject (when applicable, parental/legal representative) must understand and voluntarily sign an ICF/IAF prior to any study-related assessments/procedures being conducted.
• Subject has received at least one prior standard therapy (or generally accepted upfront therapy if no standard exists) and have no known curative therapy.
• 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 they meet all other eligibility criteria.
• 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
• 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)
• 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.
• Subject has Karnofsky (age ≥ 16 years) or Lansky (age \< 16 years) performance status score ≥ 50 at screening
• Subject has adequate bone marrow function defined as:
• Peripheral absolute neutrophil count (ANC) ≥ 1000/mm³
• 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)
• Subject has adequate renal function defined as:
• Serum creatinine based on age/gender calculated using the Schwartz formula, or a 24-hour creatinine clearance or radioisotope glomerular filtration rate (GFR) (radioisotope or iothalamate) ≥ 70 mL/min/1.73 m².

You may not qualify if:

• Subject has a history of non-central line related thrombosis (arterial or venous), more than one prior central-line related thrombosis or known coagulopathy.
• Subject has first degree family member with a known hereditary coagulopathy.
• Subject is actively on anticoagulation therapy.
• Subject has had major (per Investigator discretion) surgery, with the exception of tumor resection, within 21 days from first dose of study drug.
• 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:

Sponsors & Collaborators

• Celgene: lead

Study Sites (22)

Stanford University Cancer Center

Stanford, California, 94305-5750, United States

Location

University Of Florida

Gainesville, Florida, 32611, United States

Location

Ann and Robert H Lurie Childrens Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Local Institution - 506

Bethesda, Maryland, 20892, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Local Institution - 104

Lille, Nord, 59020, France

Location

Local Institution - 102

Lyon, 69008, France

Location

Local Institution - 103

Marseille, 13005, France

Location

Local Institution - 100

Paris, 75005, France

Location

Local Institution - 106

Toulouse, 31059, France

Location

Local Institution - 105

Vandœuvre-lès-Nancy, 54511, France

Location

Local Institution - 101

Villejuif, 94805, France

Location

Local Institution - 201

Genova, 0, Italy

Location

Local Institution - 200

Milan, 20133, Italy

Location

Local Institution - 202

Roma, 00165, Italy

Location

Local Institution - 302

Barcelona, 8035, Spain

Location

Local Institution - 300

Madrid, 28009, Spain

Location

Local Institution - 301

Valencia, 46026, Spain

Location

Local Institution - 400

Leeds, LS7 4SA, United Kingdom

Location

Local Institution - 403

London, WC1N 3JH, United Kingdom

Location

Local Institution - 401

Sutton-Surrey, SM2 5PT, United Kingdom

Location

Related Publications (2)

• Fangusaro J, Cefalo MG, Garre ML, Marshall LV, Massimino M, Benettaib B, Biserna N, Poon J, Quan J, Conlin E, Lewandowski J, Simcock M, Jeste N, Hargrave DR, Doz F, Warren KE. Phase 2 Study of Pomalidomide (CC-4047) Monotherapy for Children and Young Adults With Recurrent or Progressive Primary Brain Tumors. Front Oncol. 2021 Jun 8;11:660892. doi: 10.3389/fonc.2021.660892. eCollection 2021.

  PMID: 34168987 DERIVED

• Fangusaro J, Mitchell DA, Kocak M, Robinson GW, Baxter PA, Hwang EI, Huang J, Onar-Thomas A, Dunkel IJ, Fouladi M, Warren KE. Phase 1 study of pomalidomide in children with recurrent, refractory, and progressive central nervous system tumors: A Pediatric Brain Tumor Consortium trial. Pediatr Blood Cancer. 2021 Feb;68(2):e28756. doi: 10.1002/pbc.28756. Epub 2020 Oct 7.

  PMID: 33025730 DERIVED

Related Links

• BMS Clinical Trial Information

MeSH Terms

Conditions

Central Nervous System Neoplasms; Medulloblastoma; Brain Neoplasms; Glioma; Ependymoma

Interventions

pomalidomide

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Diseases; Central Nervous System Diseases

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please Email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: August 18, 2017
• First Posted: August 22, 2017
• Study Start: September 18, 2017
• Primary Completion: September 14, 2023
• Study Completion: September 14, 2023
• Last Updated: April 16, 2024
• Results First Posted: December 10, 2019

Record last verified: 2024-04

Locations

US (6); ES (3); GB (3); FR (7); IT (3)