Trial of Nivolumab Following Partially Human Leukocyte Antigen (HLA) Mismatched BMT in Children & Adults With Sarcoma

NCT03465592 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: J17124IRB00143746
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 4

Brief Summary

This research is being done to find out if an investigational drug, Nivolumab, can be safely administered after a "half-matched" (haplo) bone marrow transplant (BMT), and if the investigational drug will help to prevent or delay relapse or progression of sarcomas. In this study investigators will also be trying to learn more about how the investigational drug changes blood and/or tumors. Participants are eligible for this trial if they have recently undergone a "half-matched" (haplo) bone marrow transplant and have either relapsed or are at high risk to relapse.

Conditions

Sarcoma; Solid Tumor, Adult; Solid Tumor, Childhood

Outcome Measures

Primary Outcomes (1)

• Adverse events attributed to Nivolumab for patients enrolled in this study

  Cumulative adverse events from Nivolumab therapy administered after reduced intensity conditioning (RIC) haploidentical bone marrow transplant (haploBMT) in children and young adults with high risk sarcomas at the time of relapse (part A) or pre-emptively (part B).

  4 years

Secondary Outcomes (1)

• Overall survival

  4 years

Study Arms (1)

Nivolumab

EXPERIMENTAL

Adults: 240 mg IV over 30 minutes every 2 weeks OR 480 mg IV over 30 minutes every 4 weeks. Children and Adolescents weighing 40 kg or more: 240 mg IV over 30 minutes every 2 weeks OR 480 mg IV over 30 minutes every 4 weeks. Children and Adolescents weighing less than 40 kg: 3 mg/kg IV over 30 minutes every 2 weeks.A maximum of 24 cycles will be given on study.

Drug: Nivolumab

Interventions

Nivolumab DRUG

Administered IV

Also known as: BMS-936558, MDX1106, ONO-4538

Nivolumab

Eligibility Criteria

• Age: 12 Months - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must be ≥ 12 months and ≤ 50 years of age at the time of study enrollment.
• Patients with histologically confirmed solid tumors with an estimated poor long term survival.
• Performance Level: Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 60 for patients ≤16 years of age.
• Patients must be post RIC haploidentical BMT.
• Patients must have fully recovered from the acute toxic effects of prior BMT.
• Concomitant radiation therapy can be administered in the setting of this trial.
• Subjects must consent to allow for a baseline tumor biopsy. If a biopsy is not feasible, then archival tumor material must be made available. Tumor biopsies to be taken (if a subject's tumor is thought to be reasonably safe and easy to biopsy) at baseline (any time prior to the first dose after eligibility is met) and at Cycle 2 (4-6 cores per time point) or when lesions are visualized on physical examination or imaging studies in the case of no identifiable masses at cycle 2. Additional optional biopsies may be obtained later in the course of study treatment. The proposed investigation is considered a non-significant risk (NSR). A significant risk procedure is generally considered to be one for which the procedure-associated absolute risk of mortality or major morbidity, in the patient's clinical setting and at the institution completing the procedure, is 2% or higher. Diagnostic Tissue Samples Tissue, fluid, or blood may be collected from standard of care procedures used to treat or diagnose immune related toxicities/GVHD.
• Organ Function Requirements:
• I. Adequate Hematologic Parameters:
• For patients with solid tumors without known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) ≥ 500/mm3
• Platelet count ≥ 50,000/mm3
• Patients with known bone marrow metastatic disease will be eligible for study without the above criteria. They may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions. These patients will not be evaluable for hematologic toxicity.
• II. Adequate Renal Function Defined as:
• Creatinine clearance or radioisotope Glomerular filtration rate (GFR) ≥ 70ml/min/1.73 m2 or

You may not qualify if:

• GVHD: any history of Stage 4 skin GVHD or Stage 3 gut/liver GVHD (a.k.a. overall Grade III/IV GVHD) or any severe chronic GVHD. Any person with ≤ Grade II GVHD must be off systemic immunosuppressive therapy for at least 2 weeks prior to receiving Nivolumab therapy.
• Inhaled or topical steroids and adrenal replacement steroid doses are permitted in the absence of active auto- or allo-immune disease
• BMT-related toxicities: patients who developed idiopathic pneumonia syndrome (IPS) or veno-occlusive hepatic disease (VOD) must be off systemic immunosuppression and/or defibrotide for at least 14 days to be eligible.
• Infection: Patients who have an uncontrolled infection.
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
• Has active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Allergies and Adverse Drug Reaction
• History of allergy to study drug components.
• History of severe hypersensitivity reaction to any monoclonal antibody.
• Pregnancy or Breast Feeding: Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of study treatment with nivolumab and 5 months after the last dose of study treatment {i.e., 30 days (duration of ovulatory cycle) plus the time required for the investigational drug to undergo approximately five half-lives. Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment with nivolumab and 7 months after the last dose of study treatment {i.e., 90 days (duration of sperm turnover) plus the time required for the investigational drug to undergo approximately five half-lives.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Bristol-Myers Squibb: collaborator

Study Sites (4)

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

ACTIVE NOT RECRUITING

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

RECRUITING

Albert Einstein College of Medicine, Children's Hospital at Montefiore

The Bronx, New York, 10467, United States

RECRUITING

New York Medical Center/ Maria Fareri Children's Hospital

Valhalla, New York, 10595, United States

RECRUITING

MeSH Terms

Conditions

Sarcoma

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Nicolas Llosa, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Megan Petrycki, RN

CONTACT

410-955-0432; mpetryc1@jhmi.edu

Tammy Scott, RN

CONTACT

410-614-5990; scottta@jhmi.edu

Study Design

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

Model Details: Adults: 240 mg IV (in a vein) over 30 minutes every 2 weeks OR 480 mg IV over 30 minutes every 4 weeks. Children and Adolescents weighing 40 kg or more: 240 mg IV over 30 minutes every 2 weeks OR 480 mg IV over 30 minutes every 4 weeks. Children and Adolescents weighing less than 40 kg: 3 mg/kg IV over 30 minutes every 2 weeks. A maximum of 24 cycles will be given on study. Participants may continue to receive Nivolumab unless they develop serious side effects or the tumor worsens. There were two parts to this study. The first part, Part A, was for patients who have relapsed or have progressive disease after their BMT. Part A is now closed. The second part, Part B, is for patients who have not yet relapsed or progressed after BMT.

Study Record Dates

• First Submitted: March 2, 2018
• First Posted: March 14, 2018
• Study Start: May 1, 2018
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): March 1, 2029
• Last Updated: February 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)