Durvalumab in Pediatric and Adolescent Patients

NCT02793466 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CHLA-16-00177
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial is the first clinical trial to study Durvalumab, a checkpoint inhibitor which stimulates the patient's own immune system to act against cancer cells in children and adolescents. This trial will assess the safety and tolerability of Durvalumab in children and adolescents and also study how Durvalumab is processed in their bodies.

Conditions

Solid Tumor; Lymphoma; Central Nervous System Tumors

Keywords

Durvalumab; solid tumors; Immunotherapy; Check Point Inhibitor; pediatrics; children

Outcome Measures

Primary Outcomes (6)

• Maximum Tolerated Dose (MTD)

  Maximum dose of Durvalumab in milligrams per kilogram body weight that can be administered to children between the age of 1 and 18 years that will be used to study the drug further in a Phase 2 clinical trial in a population of the same age distribution

  28 days

• Dose Limiting Toxicity (DLT)

  Number of patients with dose limiting toxicity

  28 days

• Safety Profile

  Number of patients with Adverse events

  Up to 15 months

• Maximum Plasma Concentration (CMax)

  Durvalumab levels micrograms/mL

  Up to 7 months

• Area under the curve (AUC)

  time and Durvalumab levels days-micrograms/mL

  14 days

• Minimum Plasma Concentration (CTrough)

  Durvalumab levels in micrograms/mL

  Up to 15 months

Secondary Outcomes (4)

• Response rate

  8 weeks

• Drug antibody level

  18 months

• Suppression of free soluble PD-L1 suppression in serum

  15 months

• Duration of response

  up to 2 years

Study Arms (1)

Durvalumab; MEDI4736

EXPERIMENTAL

Open label

Drug: Durvalumab; MEDI4736

Interventions

Durvalumab; MEDI4736 DRUG

IV Infusion every 2 weeks for a maximum of 26

Also known as: Durvalumab

Durvalumab; MEDI4736

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age: Patients must be \>12 months and \<18 years of age at the time of study enrollment.
• Diagnosis: Patient must have disease that is either refractory to frontline treatment or have relapsed. Patient must have had histologic verification of a solid tumor (including lymphoma and CNS tumors) at the time of original diagnosis or relapse with the following exceptions:
• Patients with germ cell tumors (both CNS and non-CNS) that have elevated tumor markers (e.g. α-fetoprotein, β-human chorionic gonadotropin, inhibin A/B) and radiographic evidence of disease.
• Patients with diffuse intrinsic pontine glioma (DIPG) diagnosed by radiographic studies.
• Disease Status: Patients must have either measurable or evaluable disease that can be accurately assessed at baseline by computerized tomography (CT) or magnetic resonance imaging (MRI) and is suitable for repeated assessment with the following exception:
• Patients with a third relapse of osteosarcoma and no measurable disease after surgical resection will be eligible for this study.
• Therapeutic Options: Patient's current disease state must be one for which there is no known curative therapy.
• Performance Level: Karnofsky ≥ 50 for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who can actively sit up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. See Appendix I for scoring guidelines.
• Organ Function Requirements:
• Adequate organ and bone marrow function as defined below:
• Absolute neutrophil count ≥ 750/mm3
• Platelets ≥ 75,000/mm3 . Patients must be transfusion independent and should not have received a platelet transfusion within 5 days of enrollment.
• Hemoglobin ≥8.0 g/dL. Patients may receive PRBC transfusion.
• Adequate renal function as defined by: Creatinine clearance or radioisotope GFR \> 70ml/min/m 2
• Total serum bilirubin (conjugated plus unconjugated) ≤1.5 x upper limit of normal (ULN) for age. For patients with Hepatocellular Carcinoma (HCC) or patients with documented/suspected Gilbert's disease, bilirubin ≤3x ULN.

You may not qualify if:

• Prior therapy:
• Nitrosourea or mitomycin C within 6 weeks of the first dose of study treatment.
• Any investigational agents or study drugs from a previous clinical study within 28 days of the first dose of study treatment. Patient may be enrolled in other non-therapeutic studies.
• Hematopoietic growth factors: Within 14 days of the last dose of a long acting growth factor (e.g. Neulasta) or within 7 days of receiving a short acting growth factor. This does not apply to erythropoetin.
• Monoclonal antibodies: Less than 3 half-lives or 28 days (whichever is shorter) after the last dose of monoclonal antibody, and without resolution of all known toxicity of the antibody.
• Any other chemotherapy, immunotherapy or anticancer agents within 4 weeks of the first dose of study treatment. For agents with known adverse events occurring beyond 3 weeks of administration after administration, this period must be extended beyond the time during which adverse events are known to occur.
• Any previous systemic exposure to a PD-1 or PD-L1 inhibitor, including Durvalumab.
• Major surgery (excluding placement of vascular access and needle biopsies) within 2 weeks of the first dose of study treatment.
• Radiotherapy within two weeks for local palliative XRT or within 6 weeks if craniospinal XRT or if ≥ 50% radiation of pelvis.
• Current or prior use of immunosuppressive medication within 28 days before the first dose of Durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
• Any prior allogeneic BMT/HSCT.
• Autologous BMT/HSCT within 90 days.
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTc) \> 470 msec obtained from at least 2 electrocardiograms (ECGs).
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block)

Sponsors & Collaborators

• Leo Mascarenhas: lead

Study Sites (1)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

MeSH Terms

Conditions

Lymphoma; Central Nervous System Neoplasms

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases

Study Officials

• Leo Mascarenhas

  Children's Hospital Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 22, 2016
• First Posted: June 8, 2016
• Study Start: July 1, 2016
• Primary Completion: November 30, 2022
• Study Completion: April 30, 2023
• Last Updated: September 22, 2023

Record last verified: 2023-09

Locations

US (1)