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Pepinemab in Treating Younger Patients With Recurrent, Relapsed, or Refractory Solid Tumors

Sponsor
Children's Oncology Group (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03320330
Collaborator
National Cancer Institute (NCI) (NIH)
26
Enrollment
24
Locations
1
Arm
95.6
Anticipated Duration (Months)
1.1
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase I/II trial studies the side effects and best dose of pepinemab and to see how well it works in treating younger patients with solid tumors that have come back after treatment, or do not respond to treatment. Immunotherapy with monoclonal antibodies, such as pepinemab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Condition or Disease Intervention/Treatment Phase
  • Other: Laboratory Biomarker Analysis
  • Biological: Pepinemab
  • Other: Pharmacological Study
 Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose of pepinemab (VX15/2503) administered as an intravenous infusion every 14 days to children with recurrent or refractory solid tumors. (Part A) II. To define and describe the toxicities of VX15/2503 administered on this schedule. (Parts A-B) III. To characterize the pharmacokinetics of VX15/2503 in children with recurrent or refractory cancer. (Parts A-B) IV. To preliminarily define the antitumor activity of VX15/2503 for the treatment of relapsed or refractory osteosarcoma. (Part B) V. To determine if VX15/2503 either improves the disease control rate at 4 months in patients with recurrent measurable osteosarcoma or produces an objective response rate in patients with relapsed or refractory osteosarcoma. (Part B)
SECONDARY OBJECTIVES:

  1. To assess the pharmacodynamics of VX15/2503 through VX15/2503 saturation of T-lymphocytes.

  2. To assess the immunogenicity of VX15/2503 in pediatric patients with recurrent or refractory cancer.

EXPLORATORY OBJECTIVES:
  1. To evaluate potential biomarkers of VX15/2503 sensitivity including SEMA4D, PlexinB1, and other markers of immune cell infiltration in archival tumor tissues.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive pepinemab intravenously (IV) over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Study Design

Study Type:
Interventional
Actual Enrollment :
26 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2 Study of VX15/2503 in Children, Adolescents, or Young Adults With Recurrent or Relapsed Solid Tumors
Actual Study Start Date :
Jan 12, 2018
Actual Primary Completion Date :
Dec 31, 2020
Anticipated Study Completion Date :
Dec 31, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (pepinemab)

Patients receive pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Pepinemab
Given IV
Other Names:
  • moAb VX15/2503
  • VX15/2503

    • Other: Pharmacological Study
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Dose Limiting Toxicities [Up to 28 days]

      Frequency (%) of patients with dose limiting toxicities by dose level and study part.

    2. Patients Who Had Grade 3 or Above Toxicities With the Three Attributions, 'DEFINITE', 'POSSIBLE','PROBABLE' [Up to 28 days]

      Frequency of patients experiencing at least grade 3 toxicity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 by dose level and study part.

    3. Half-life [Prior to, at the end of, and 2 hours after infusion on day 1 of cycles 1-2; days 4 & 8 of cycle 1; prior to and the end of infusion on day 15 of cycle 1; prior to start of infusion on day 15 of cycle 2; prior to start of infusion on day 1 of cycles 3+]

      Mean and standard deviation for the time required for the serum concentration to fall to 50% of its starting dose by dose level and study part.

    4. Time to Maximum Concentration (T Max) [Prior to, at the end of, and 2 hours after infusion on day 1 of cycles 1-2; days 4 & 8 of cycle 1; prior to and the end of infusion on day 15 of cycle 1; prior to start of infusion on day 15 of cycle 2; prior to start of infusion on day 1 of cycles 3+]

      Mean and standard deviation for the time at which the maximum (peak) serum concentration occurs by dose level and study part.

    5. Maximum Concentration (C Max) [Prior to, at the end of, and 2 hours after infusion on day 1 of cycles 1-2; days 4 & 8 of cycle 1; prior to and the end of infusion on day 15 of cycle 1; prior to start of infusion on day 15 of cycle 2; prior to start of infusion on day 1 of cycles 3+]

      Mean and standard deviation for the maximum (peak) serum concentration by dose level and study part.

    6. Area Under Curve (AUC) [Prior to, at the end of, and 2 hours after infusion on day 1 of cycles 1-2; days 4 & 8 of cycle 1; prior to and the end of infusion on day 15 of cycle 1; prior to start of infusion on day 15 of cycle 2; prior to start of infusion on day 1 of cycles 3+]

      Mean and standard deviation for the area under the drug concentration over time curve by dose level and study part.

    7. Clearance [Prior to, at the end of, and 2 hours after infusion on day 1 of cycles 1-2; days 4 & 8 of cycle 1; prior to and the end of infusion on day 15 of cycle 1; prior to start of infusion on day 15 of cycle 2; prior to start of infusion on day 1 of cycles 3+]

      Mean and standard deviation for the rate of elimination of the drug by dose level and study part.

    8. Disease Control Rate (Part A) [Up to 4 months]

      Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no new lesions detected and <20% increase in sum of smallest diameters of lesions; Disease Control Rate = CR + PR + SD

    9. Response (Complete Response or Partial Response) (Part B) [Up to 168 days]

      Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no new lesions detected and <20% increase in sum of smallest diameters of lesions; Disease Control Rate = CR + PR + SD

    Secondary Outcome Measures

    1. T-lymphocyte Saturation [Up to 3 years]

      Mean and standard deviation for blood samples that will be evaluated for T-lymphocyte saturation by VX15/2503 utilizing a validated flow-cytometry based assay.

    2. Total Soluble SEMA4D [Up to 3 years]

      Mean and standard deviation of blood and serum samples evaluated for total soluble SEMA4D through a qualified enzyme-linked immunosorbent assay (ELISA) assay.

    3. Immunogenicity of Pepinemab [Up to 3 years]

      Mean and standard deviation of immunogenicity assessed in serum through a qualified ELISA.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Months to 30 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Part A: Patients with recurrent or refractory solid tumors are eligible, excluding central nervous system (CNS) tumors; patients must have had histologic verification of malignancy at original diagnosis or relapse

    • Part B: Patients with recurrent or refractory osteosarcoma are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse

    • Part A: Patients must have either measurable or evaluable disease

    • Part B: Patients must have measurable disease

    • Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life

    • 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 are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score

    • Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately

    • Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive

    • = 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)

    • Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent

    • Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1

    • Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid

    • Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator

    • Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)

    • Stem cell Infusions (with or without total body irradiation [TBI]):

    • Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion:

    = 84 days after infusion and no evidence of graft versus host disease (GVHD)

    • Autologous stem cell infusion including boost infusion: >= 42 days

    • Cellular Therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)

    • Radiation Therapy (XRT)/External Beam Irradiation including Protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation

    • Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy

    • Patients must not have received prior exposure to VX15/2503

    • Peripheral absolute neutrophil count (ANC) >= 1000/mm^3

    • Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)

    • Hemoglobin >= 8.0 g/dL at baseline (may receive red blood cell [RBC] transfusions)

    • Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts above (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; at least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study; if dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity

    • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or

    • A serum creatinine based on age/gender as follows:

    • Age: 1 to < 2 years; Male: 0.6 mg/dL; Female: 0.6 mg/dL

    • Age: 2 to < 6 years; Male: 0.8 mg/dL; Female: 0.8 mg/dL

    • Age: 6 to < 10 years; Male: 1 mg/dL; Female: 1 mg/dL

    • Age: 10 to < 13 years; Male: 1.2 mg/dL; Female: 1.2 mg/dL

    • Age: 13 to < 16 years; Male: 1.5 mg/dL; Female: 1.4 mg/dL

    • Age: >= 16 years; Male: 1.7 mg/dL; Female: 1.4 mg/dL

    • Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age

    • Alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) =< 135 U/L; for the purpose of this study, the ULN for ALT is 45 U/L

    • Serum albumin >= 2 g/dL

    • No clinical indications such as evidence of dyspnea at rest, or exercise intolerance due to pulmonary insufficiency

    • If clinical indications, pulse oximetry > 94% on room air

    • All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines

    • Tissue blocks or slides must be sent; if tissue blocks or slides are unavailable, the study chair must be notified prior to enrollment

    Exclusion Criteria:

    • Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study; abstinence is an acceptable method of birth control

    • Patients receiving systemic corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of systemic corticosteroid; Note: patients who are using topical or inhaled corticosteroids are eligible

    • Patients who are currently receiving another investigational drug are not eligible

    • Patients who are currently receiving other anti-cancer agents are not eligible (except leukemia patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy)

    • Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial

    • Patients who have an uncontrolled infection are not eligible

    • Patients who have received a prior solid organ transplantation are not eligible

    • 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Children's Hospital of Alabama Birmingham Alabama United States 35233
    2 Children's Hospital Los Angeles Los Angeles California United States 90027
    3 Children's Hospital of Orange County Orange California United States 92868
    4 UCSF Medical Center-Mission Bay San Francisco California United States 94158
    5 Children's Hospital Colorado Aurora Colorado United States 80045
    6 Yale University New Haven Connecticut United States 06520
    7 Children's National Medical Center Washington District of Columbia United States 20010
    8 Children's Healthcare of Atlanta - Egleston Atlanta Georgia United States 30322
    9 Lurie Children's Hospital-Chicago Chicago Illinois United States 60611
    10 Riley Hospital for Children Indianapolis Indiana United States 46202
    11 Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland United States 21287
    12 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
    13 C S Mott Children's Hospital Ann Arbor Michigan United States 48109
    14 University of Minnesota/Masonic Cancer Center Minneapolis Minnesota United States 55455
    15 Washington University School of Medicine Saint Louis Missouri United States 63110
    16 NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center New York New York United States 10032
    17 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229
    18 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    19 Children's Hospital of Pittsburgh of UPMC Pittsburgh Pennsylvania United States 15224
    20 Saint Jude Children's Research Hospital Memphis Tennessee United States 38105
    21 Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center Houston Texas United States 77030
    22 University of Texas Health Science Center at San Antonio San Antonio Texas United States 78229
    23 Children's Hospital of The King's Daughters Norfolk Virginia United States 23507
    24 Seattle Children's Hospital Seattle Washington United States 98105

    Sponsors and Collaborators

    • Children's Oncology Group
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Emily G Greengard, COG Phase I Consortium

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Children's Oncology Group
    ClinicalTrials.gov Identifier:
    NCT03320330
    Other Study ID Numbers:
    • ADVL1614
    • NCI-2017-01103
    • ADVL1614
    • ADVL1614
    • UM1CA097452
    First Posted:
    Oct 25, 2017
    Last Update Posted:
    Apr 26, 2022
    Last Verified:
    Apr 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Neoplasms
    Osteosarcoma
    Recurrence

    Study Results

    Participant Flow

    Recruitment Details A Phase I/II Study of VX15/2503 in Children, Adolescents, or Young Adults with Recurrent or Relapsed Solid Tumors. This trial studies the side effects and best dose of pepinemab to see how well it works in treating younger patients that have come back after treatment, or do not respond to treatment. Immunotherapy with monoclonal antibodies, such as pepinemab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
    Pre-assignment Detail Part A (phase 1) portion of the study was to determine if Dose Level 1 (DL1), 20mg/kg pepinemab, was the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D). There were no dose levels above DL1. However, there was a possible lower dose level of 10mg/kg pepinemab if DL1 was too toxic. Since were no patients with dose-limiting toxicities, all patients in Part A PK (Expansion) and Part B (phase 2) received 20mg/kg pepinemab
    Arm/Group Title Part A: 20 mg/kg (Phase 1) Part A PK: 20 mg/kg (Expansion) Part B: 20 mg/kg (Phase 2)
    Arm/Group Description Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies Patients ≥ 12 months and ≤ 30 years with recurrent or refractory osteosarcoma, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
    Period Title: Overall Study
    STARTED 6 6 14
    COMPLETED 0 1 0
    NOT COMPLETED 6 5 14

    Baseline Characteristics

    Arm/Group Title Part A Part A PK Part B Total
    Arm/Group Description Patients must be ≥ 12 months and ≤ 21 years of age, recurrent or refractory solid tumors are eligible, excluding CNS tumors. Patients must be ≥ 12 months and ≤ 21 years of age, recurrent or refractory solid tumors are eligible, excluding CNS tumors. Patients must be ≥ 12 months and ≤ 21 years of age, recurrent or refractory solid tumors are eligible, excluding CNS tumors. Total of all reporting groups
    Overall Participants 6 6 14 26
    Age (Count of Participants)
    <=18 years
    4
    66.7%
    6
    100%
    6
    42.9%
    16
    61.5%
    Between 18 and 65 years
    2
    33.3%
    0
    0%
    8
    57.1%
    10
    38.5%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Age (Year) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Year]
    17.5
    (2.3)
    7.7
    (4.2)
    17.4
    (7.1)
    15.2
    (7)
    Sex: Female, Male (Count of Participants)
    Female
    2
    33.3%
    2
    33.3%
    8
    57.1%
    12
    46.2%
    Male
    4
    66.7%
    4
    66.7%
    6
    42.9%
    14
    53.8%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    16.7%
    1
    16.7%
    4
    28.6%
    6
    23.1%
    Not Hispanic or Latino
    5
    83.3%
    4
    66.7%
    8
    57.1%
    17
    65.4%
    Unknown or Not Reported
    0
    0%
    1
    16.7%
    2
    14.3%
    3
    11.5%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    1
    16.7%
    0
    0%
    1
    3.8%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    1
    16.7%
    2
    14.3%
    3
    11.5%
    White
    2
    33.3%
    3
    50%
    7
    50%
    12
    46.2%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    4
    66.7%
    1
    16.7%
    5
    35.7%
    10
    38.5%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Dose Limiting Toxicities
    Description Frequency (%) of patients with dose limiting toxicities by dose level and study part.
    Time Frame Up to 28 days

    Outcome Measure Data

    Analysis Population Description
    The patients who had DLT in dose escalation course.
    Arm/Group Title Part A: 20 mg/kg (Phase 1) Part A PK: 20 mg/kg (Expansion) Part B: 20 mg/kg (Phase 2)
    Arm/Group Description Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies Patients ≥ 12 months and ≤ 30 years with recurrent or refractory osteosarcoma, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
    Measure Participants 6 6 14
    Count of Participants [Participants]
    0
    0%
    0
    0%
    1
    7.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Part A: 20 mg/kg (Phase 1)
    Comments
    Type of Statistical Test Other
    Comments Recommended Phase 2 dose of pepinemab (VX15/2503), administered to children with recurrent or refractory solid tumors (Part A), was determined by the rolling-6 design.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Recommended Phase 2 dose
    Estimated Value 20
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Recommended Phase 2 dose of pepinemab (VX15/2503) is 20 mg/kg.
    2. Primary Outcome
    Title Patients Who Had Grade 3 or Above Toxicities With the Three Attributions, 'DEFINITE', 'POSSIBLE','PROBABLE'
    Description Frequency of patients experiencing at least grade 3 toxicity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 by dose level and study part.
    Time Frame Up to 28 days

    Outcome Measure Data

    Analysis Population Description
    Part A and B Patients
    Arm/Group Title Part A: 20 mg/kg (Phase 1) Part A PK: 20 mg/kg (Expansion) Part B: 20 mg/kg (Phase 2)
    Arm/Group Description Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies Patients ≥ 12 months and ≤ 30 years with recurrent or refractory osteosarcoma, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
    Measure Participants 6 6 14
    Count of Participants [Participants]
    0
    0%
    1
    16.7%
    3
    21.4%
    3. Primary Outcome
    Title Half-life
    Description Mean and standard deviation for the time required for the serum concentration to fall to 50% of its starting dose by dose level and study part.
    Time Frame Prior to, at the end of, and 2 hours after infusion on day 1 of cycles 1-2; days 4 & 8 of cycle 1; prior to and the end of infusion on day 15 of cycle 1; prior to start of infusion on day 15 of cycle 2; prior to start of infusion on day 1 of cycles 3+

    Outcome Measure Data

    Analysis Population Description
    all toxicity evaluable patients
    Arm/Group Title Part A: 20 mg/kg (Phase 1) Part A PK: 20 mg/kg (Expansion) Part B: 20 mg/kg (Phase 2)
    Arm/Group Description Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies Patients ≥ 12 months and ≤ 30 years with recurrent or refractory osteosarcoma, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
    Measure Participants 6 6 13
    Mean (Standard Deviation) [hours]
    281
    (176)
    221
    (48)
    162
    (64)
    4. Primary Outcome
    Title Time to Maximum Concentration (T Max)
    Description Mean and standard deviation for the time at which the maximum (peak) serum concentration occurs by dose level and study part.
    Time Frame Prior to, at the end of, and 2 hours after infusion on day 1 of cycles 1-2; days 4 & 8 of cycle 1; prior to and the end of infusion on day 15 of cycle 1; prior to start of infusion on day 15 of cycle 2; prior to start of infusion on day 1 of cycles 3+

    Outcome Measure Data

    Analysis Population Description
    All toxicity evaluable patients
    Arm/Group Title Part A: 20 mg/kg (Phase 1) Part A PK: 20 mg/kg (Expansion) Part B: 20 mg/kg (Phase 2)
    Arm/Group Description Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies Patients ≥ 12 months and ≤ 30 years with recurrent or refractory osteosarcoma, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
    Measure Participants 6 6 13
    Mean (Standard Deviation) [hours]
    1.9
    (1.1)
    1.7
    (1)
    1.7
    (0.9)
    5. Primary Outcome
    Title Maximum Concentration (C Max)
    Description Mean and standard deviation for the maximum (peak) serum concentration by dose level and study part.
    Time Frame Prior to, at the end of, and 2 hours after infusion on day 1 of cycles 1-2; days 4 & 8 of cycle 1; prior to and the end of infusion on day 15 of cycle 1; prior to start of infusion on day 15 of cycle 2; prior to start of infusion on day 1 of cycles 3+

    Outcome Measure Data

    Analysis Population Description
    All toxicity evaluable patients
    Arm/Group Title Part A: 20 mg/kg (Phase 1) Part A PK: 20 mg/kg (Expansion) Part B: 20 mg/kg (Phase 2)
    Arm/Group Description Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies Patients ≥ 12 months and ≤ 30 years with recurrent or refractory osteosarcoma, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
    Measure Participants 6 6 13
    Mean (Standard Deviation) [ug/ml]
    175
    (78)
    203
    (85)
    168
    (75)
    6. Primary Outcome
    Title Area Under Curve (AUC)
    Description Mean and standard deviation for the area under the drug concentration over time curve by dose level and study part.
    Time Frame Prior to, at the end of, and 2 hours after infusion on day 1 of cycles 1-2; days 4 & 8 of cycle 1; prior to and the end of infusion on day 15 of cycle 1; prior to start of infusion on day 15 of cycle 2; prior to start of infusion on day 1 of cycles 3+

    Outcome Measure Data

    Analysis Population Description
    All toxicity evaluable patients
    Arm/Group Title Part A: 20 mg/kg (Phase 1) Part A PK: 20 mg/kg (Expansion) Part B: 20 mg/kg (Phase 2)
    Arm/Group Description Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies Patients ≥ 12 months and ≤ 30 years with recurrent or refractory osteosarcoma, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
    Measure Participants 6 6 13
    Mean (Standard Deviation) [hr*ug/ml]
    46913
    (29902)
    41328
    (9251)
    36811
    (17641)
    7. Primary Outcome
    Title Clearance
    Description Mean and standard deviation for the rate of elimination of the drug by dose level and study part.
    Time Frame Prior to, at the end of, and 2 hours after infusion on day 1 of cycles 1-2; days 4 & 8 of cycle 1; prior to and the end of infusion on day 15 of cycle 1; prior to start of infusion on day 15 of cycle 2; prior to start of infusion on day 1 of cycles 3+

    Outcome Measure Data

    Analysis Population Description
    All toxicity evaluable patients
    Arm/Group Title Part A: 20 mg/kg (Phase 1) Part A PK: 20 mg/kg (Expansion) Part B: 20 mg/kg (Phase 2)
    Arm/Group Description Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies Patients ≥ 12 months and ≤ 30 years with recurrent or refractory osteosarcoma, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
    Measure Participants 6 6 13
    Mean (Standard Deviation) [ml/hr]
    40.03
    (34.9)
    13.4
    (4.6)
    33.2
    (25.3)
    8. Primary Outcome
    Title Disease Control Rate (Part A)
    Description Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no new lesions detected and <20% increase in sum of smallest diameters of lesions; Disease Control Rate = CR + PR + SD
    Time Frame Up to 4 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Part A: 20 mg/kg (Phase 1) Part A PK: 20 mg/kg (Expansion)
    Arm/Group Description Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
    Measure Participants 6 6
    Number [participants]
    0
    0%
    0
    0%
    9. Primary Outcome
    Title Response (Complete Response or Partial Response) (Part B)
    Description Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no new lesions detected and <20% increase in sum of smallest diameters of lesions; Disease Control Rate = CR + PR + SD
    Time Frame Up to 168 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Part B: 20 mg/kg (Phase 2)
    Arm/Group Description Patients ≥ 12 months and ≤ 30 years with recurrent or refractory osteosarcoma, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
    Measure Participants 14
    Number [participants]
    0
    0%
    10. Secondary Outcome
    Title T-lymphocyte Saturation
    Description Mean and standard deviation for blood samples that will be evaluated for T-lymphocyte saturation by VX15/2503 utilizing a validated flow-cytometry based assay.
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    11. Secondary Outcome
    Title Total Soluble SEMA4D
    Description Mean and standard deviation of blood and serum samples evaluated for total soluble SEMA4D through a qualified enzyme-linked immunosorbent assay (ELISA) assay.
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    12. Secondary Outcome
    Title Immunogenicity of Pepinemab
    Description Mean and standard deviation of immunogenicity assessed in serum through a qualified ELISA.
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame Up to 28 months
    Adverse Event Reporting Description Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
    Arm/Group Title Part A: 20 mg/kg (Phase 1) Part A PK: 20 mg/kg (Expansion) Part B: 20 mg/kg (Phase 2)
    Arm/Group Description Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies Patients ≥ 12 months and ≤ 30 years with recurrent or refractory osteosarcoma, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
    All Cause Mortality
    Part A: 20 mg/kg (Phase 1) Part A PK: 20 mg/kg (Expansion) Part B: 20 mg/kg (Phase 2)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/6 (16.7%) 0/6 (0%) 3/14 (21.4%)
    Serious Adverse Events
    Part A: 20 mg/kg (Phase 1) Part A PK: 20 mg/kg (Expansion) Part B: 20 mg/kg (Phase 2)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/6 (66.7%) 4/6 (66.7%) 10/14 (71.4%)
    Blood and lymphatic system disorders
    Anemia 1/6 (16.7%) 1/6 (16.7%) 6/14 (42.9%)
    Cardiac disorders
    Pericardial effusion 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Ear and labyrinth disorders
    Hearing impaired 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Gastrointestinal disorders
    Esophagitis 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Nausea 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Vomiting 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    General disorders
    Fatigue 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Non-cardiac chest pain 1/6 (16.7%) 0/6 (0%) 1/14 (7.1%)
    Pain 1/6 (16.7%) 0/6 (0%) 1/14 (7.1%)
    Infections and infestations
    Mucosal infection 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Urinary tract infection 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Injury, poisoning and procedural complications
    Fracture 1/6 (16.7%) 1/6 (16.7%) 0/14 (0%)
    Investigations
    Alkaline phosphatase increased 0/6 (0%) 1/6 (16.7%) 1/14 (7.1%)
    Creatinine increased 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Electrocardiogram QT corrected interval prolonged 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Lymphocyte count decreased 1/6 (16.7%) 0/6 (0%) 5/14 (35.7%)
    Neutrophil count decreased 0/6 (0%) 1/6 (16.7%) 1/14 (7.1%)
    Platelet count decreased 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    White blood cell decreased 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Metabolism and nutrition disorders
    Anorexia 2/6 (33.3%) 0/6 (0%) 1/14 (7.1%)
    Dehydration 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Hyperglycemia 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Hypokalemia 1/6 (16.7%) 1/6 (16.7%) 1/14 (7.1%)
    Hyponatremia 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Hypophosphatemia 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Obesity 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Back pain 2/6 (33.3%) 0/6 (0%) 0/14 (0%)
    Myalgia 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, PROGRESSIVE DISEASE 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Nervous system disorders
    Depressed level of consciousness 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Headache 1/6 (16.7%) 0/6 (0%) 1/14 (7.1%)
    Peripheral motor neuropathy 0/6 (0%) 0/6 (0%) 2/14 (14.3%)
    Peripheral sensory neuropathy 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Syncope 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Psychiatric disorders
    Anxiety 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Renal and urinary disorders
    Acute kidney injury 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Reproductive system and breast disorders
    Irregular menstruation 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Respiratory, thoracic and mediastinal disorders
    Atelectasis 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Dyspnea 1/6 (16.7%) 0/6 (0%) 3/14 (21.4%)
    Hypoxia 1/6 (16.7%) 1/6 (16.7%) 3/14 (21.4%)
    Pleural effusion 0/6 (0%) 1/6 (16.7%) 1/14 (7.1%)
    Pneumothorax 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Respiratory failure 0/6 (0%) 1/6 (16.7%) 1/14 (7.1%)
    Vascular disorders
    Hypertension 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Thromboembolic event 2/6 (33.3%) 0/6 (0%) 0/14 (0%)
    Other (Not Including Serious) Adverse Events
    Part A: 20 mg/kg (Phase 1) Part A PK: 20 mg/kg (Expansion) Part B: 20 mg/kg (Phase 2)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/6 (100%) 6/6 (100%) 14/14 (100%)
    Blood and lymphatic system disorders
    Anemia 4/6 (66.7%) 4/6 (66.7%) 10/14 (71.4%)
    Blood and lymphatic system disorders - Other, Neutrophil count increased 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Blood and lymphatic system disorders - Other, RBC decreased 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Blood and lymphatic system disorders - Other, White Blood Cell Count Increased 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Cardiac disorders
    Pericardial effusion 1/6 (16.7%) 0/6 (0%) 1/14 (7.1%)
    Sinus bradycardia 1/6 (16.7%) 0/6 (0%) 1/14 (7.1%)
    Sinus tachycardia 5/6 (83.3%) 2/6 (33.3%) 7/14 (50%)
    Ear and labyrinth disorders
    Ear and labyrinth disorders - Other, 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Hearing impaired 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Endocrine disorders
    Cushingoid 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Hypothyroidism 0/6 (0%) 2/6 (33.3%) 0/14 (0%)
    Eye disorders
    Blurred vision 1/6 (16.7%) 0/6 (0%) 1/14 (7.1%)
    Eye disorders - Other, Anisocoria 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Eye disorders - Other, Vision decreased 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Keratitis 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Optic nerve disorder 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Photophobia 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Gastrointestinal disorders
    Abdominal distension 1/6 (16.7%) 0/6 (0%) 1/14 (7.1%)
    Abdominal pain 1/6 (16.7%) 0/6 (0%) 2/14 (14.3%)
    Constipation 2/6 (33.3%) 0/6 (0%) 5/14 (35.7%)
    Diarrhea 1/6 (16.7%) 0/6 (0%) 2/14 (14.3%)
    Dry mouth 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Dyspepsia 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Dysphagia 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Fecal incontinence 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Gastroesophageal reflux disease 1/6 (16.7%) 0/6 (0%) 2/14 (14.3%)
    Mucositis oral 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Nausea 4/6 (66.7%) 1/6 (16.7%) 7/14 (50%)
    Oral pain 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Stomach pain 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Vomiting 3/6 (50%) 1/6 (16.7%) 4/14 (28.6%)
    General disorders
    Chills 2/6 (33.3%) 1/6 (16.7%) 4/14 (28.6%)
    Edema limbs 1/6 (16.7%) 1/6 (16.7%) 3/14 (21.4%)
    Fatigue 3/6 (50%) 3/6 (50%) 6/14 (42.9%)
    Fever 3/6 (50%) 2/6 (33.3%) 10/14 (71.4%)
    Gait disturbance 2/6 (33.3%) 0/6 (0%) 2/14 (14.3%)
    General disorders and administration site conditions - Other, Generalized edema 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    General disorders and administration site conditions - Other, SWEATING 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Infusion related reaction 3/6 (50%) 2/6 (33.3%) 3/14 (21.4%)
    Infusion site extravasation 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Irritability 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Localized edema 1/6 (16.7%) 0/6 (0%) 1/14 (7.1%)
    Malaise 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Non-cardiac chest pain 1/6 (16.7%) 1/6 (16.7%) 5/14 (35.7%)
    Pain 2/6 (33.3%) 1/6 (16.7%) 3/14 (21.4%)
    Infections and infestations
    Lung infection 0/6 (0%) 1/6 (16.7%) 1/14 (7.1%)
    Upper respiratory infection 0/6 (0%) 1/6 (16.7%) 1/14 (7.1%)
    Urinary tract infection 0/6 (0%) 0/6 (0%) 2/14 (14.3%)
    Injury, poisoning and procedural complications
    Bruising 2/6 (33.3%) 0/6 (0%) 2/14 (14.3%)
    Burn 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Fall 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Infusion related reaction 3/6 (50%) 2/6 (33.3%) 2/14 (14.3%)
    Injury, poisoning and procedural complications - Other, OPEN WOUND 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Radiation recall reaction (dermatologic) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Investigations
    Activated partial thromboplastin time prolonged 0/6 (0%) 0/6 (0%) 2/14 (14.3%)
    Alanine aminotransferase increased 2/6 (33.3%) 3/6 (50%) 4/14 (28.6%)
    Alkaline phosphatase increased 6/6 (100%) 1/6 (16.7%) 8/14 (57.1%)
    Aspartate aminotransferase increased 2/6 (33.3%) 4/6 (66.7%) 4/14 (28.6%)
    Blood bilirubin increased 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Cholesterol high 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Creatinine increased 1/6 (16.7%) 0/6 (0%) 1/14 (7.1%)
    Hemoglobin increased 0/6 (0%) 0/6 (0%) 2/14 (14.3%)
    INR increased 0/6 (0%) 0/6 (0%) 2/14 (14.3%)
    Investigations - Other, BICARBONATE LOW 2/6 (33.3%) 0/6 (0%) 0/14 (0%)
    Investigations - Other, ELEVATED BICARBONATE SERUM LOW 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Investigations - Other, ELEVATED LDH 1/6 (16.7%) 0/6 (0%) 1/14 (7.1%)
    Investigations - Other, HYOCHLOREMIA 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Investigations - Other, HYPOCHLOREMIA 1/6 (16.7%) 0/6 (0%) 1/14 (7.1%)
    Investigations - Other, LDH INCREASED 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Investigations - Other, LDH increased 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Investigations - Other, Monocytes Decrease 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Investigations - Other, Monocytes Increased 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Investigations - Other, bicarbonate serum low 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Investigations - Other, elevated BUN 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Investigations - Other, elevated LDH 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Lipase increased 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Lymphocyte count decreased 0/6 (0%) 3/6 (50%) 9/14 (64.3%)
    Neutrophil count decreased 1/6 (16.7%) 1/6 (16.7%) 3/14 (21.4%)
    Platelet count decreased 0/6 (0%) 1/6 (16.7%) 5/14 (35.7%)
    Serum amylase increased 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Weight gain 0/6 (0%) 1/6 (16.7%) 1/14 (7.1%)
    Weight loss 2/6 (33.3%) 0/6 (0%) 2/14 (14.3%)
    White blood cell decreased 2/6 (33.3%) 3/6 (50%) 5/14 (35.7%)
    Metabolism and nutrition disorders
    Anorexia 2/6 (33.3%) 3/6 (50%) 7/14 (50%)
    Dehydration 2/6 (33.3%) 0/6 (0%) 0/14 (0%)
    Hyperglycemia 3/6 (50%) 4/6 (66.7%) 9/14 (64.3%)
    Hyperkalemia 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Hypermagnesemia 0/6 (0%) 1/6 (16.7%) 2/14 (14.3%)
    Hypernatremia 0/6 (0%) 0/6 (0%) 2/14 (14.3%)
    Hypoalbuminemia 3/6 (50%) 1/6 (16.7%) 8/14 (57.1%)
    Hypocalcemia 2/6 (33.3%) 1/6 (16.7%) 5/14 (35.7%)
    Hypoglycemia 1/6 (16.7%) 0/6 (0%) 2/14 (14.3%)
    Hypokalemia 1/6 (16.7%) 1/6 (16.7%) 8/14 (57.1%)
    Hypomagnesemia 2/6 (33.3%) 1/6 (16.7%) 2/14 (14.3%)
    Hyponatremia 2/6 (33.3%) 0/6 (0%) 6/14 (42.9%)
    Hypophosphatemia 1/6 (16.7%) 1/6 (16.7%) 7/14 (50%)
    Metabolism and nutrition disorders - Other, HYPOCHLOREMIA 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Metabolism and nutrition disorders - Other, Hyperchloremia 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Metabolism and nutrition disorders - Other, Increased bicarbonates 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Metabolism and nutrition disorders - Other, Increased phosphorus level 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/6 (16.7%) 1/6 (16.7%) 1/14 (7.1%)
    Back pain 2/6 (33.3%) 1/6 (16.7%) 8/14 (57.1%)
    Bone pain 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Buttock pain 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Chest wall pain 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Flank pain 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Joint range of motion decreased 1/6 (16.7%) 0/6 (0%) 4/14 (28.6%)
    Kyphosis 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Muscle weakness lower limb 0/6 (0%) 1/6 (16.7%) 4/14 (28.6%)
    Muscle weakness trunk 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Musculoskeletal and connective tissue disorder - Other, DIFFICULTY FULLY EXTENDING LEFT LEG 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Musculoskeletal and connective tissue disorder - Other, LEFT MEDIAL THIGH SWELLING 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Musculoskeletal and connective tissue disorder - Other, LIMP 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Musculoskeletal and connective tissue disorder - Other, MUSCLE ACHES/PAIN 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Musculoskeletal and connective tissue disorder - Other, muscle spasm 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Myalgia 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Neck pain 1/6 (16.7%) 1/6 (16.7%) 0/14 (0%)
    Pain in extremity 3/6 (50%) 3/6 (50%) 6/14 (42.9%)
    Nervous system disorders
    Concentration impairment 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Dizziness 0/6 (0%) 1/6 (16.7%) 1/14 (7.1%)
    Headache 2/6 (33.3%) 3/6 (50%) 7/14 (50%)
    Lethargy 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Memory impairment 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Nervous system disorders - Other, Spinal cord compression 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Neuralgia 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Paresthesia 1/6 (16.7%) 1/6 (16.7%) 2/14 (14.3%)
    Peripheral sensory neuropathy 1/6 (16.7%) 1/6 (16.7%) 3/14 (21.4%)
    Phantom pain 2/6 (33.3%) 0/6 (0%) 0/14 (0%)
    Somnolence 2/6 (33.3%) 1/6 (16.7%) 1/14 (7.1%)
    Psychiatric disorders
    Agitation 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Anxiety 3/6 (50%) 1/6 (16.7%) 7/14 (50%)
    Confusion 1/6 (16.7%) 0/6 (0%) 2/14 (14.3%)
    Depression 3/6 (50%) 2/6 (33.3%) 2/14 (14.3%)
    Hallucinations 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Insomnia 2/6 (33.3%) 0/6 (0%) 5/14 (35.7%)
    Restlessness 1/6 (16.7%) 0/6 (0%) 1/14 (7.1%)
    Renal and urinary disorders
    Hematuria 2/6 (33.3%) 1/6 (16.7%) 2/14 (14.3%)
    Hemoglobinuria 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Proteinuria 1/6 (16.7%) 2/6 (33.3%) 5/14 (35.7%)
    Urinary retention 0/6 (0%) 0/6 (0%) 3/14 (21.4%)
    Urinary urgency 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Reproductive system and breast disorders
    Breast pain 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Erectile dysfunction 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Genital edema 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Gynecomastia 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Pelvic pain 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Reproductive system and breast disorders - Other, GENITAL HYPERSENSITIVITY 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Testicular pain 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis 0/6 (0%) 1/6 (16.7%) 2/14 (14.3%)
    Atelectasis 2/6 (33.3%) 0/6 (0%) 0/14 (0%)
    Cough 4/6 (66.7%) 1/6 (16.7%) 9/14 (64.3%)
    Dyspnea 3/6 (50%) 1/6 (16.7%) 4/14 (28.6%)
    Epistaxis 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Hoarseness 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Hypoxia 0/6 (0%) 0/6 (0%) 2/14 (14.3%)
    Nasal congestion 0/6 (0%) 1/6 (16.7%) 1/14 (7.1%)
    Pleural effusion 3/6 (50%) 0/6 (0%) 6/14 (42.9%)
    Pleural hemorrhage 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Productive cough 1/6 (16.7%) 0/6 (0%) 2/14 (14.3%)
    Respiratory, thoracic and mediastinal disorders - Other, HEMOPTYSIS 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Respiratory, thoracic and mediastinal disorders - Other, Hemoptysis 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Respiratory, thoracic and mediastinal disorders - Other, MILD RHINORREA G1 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Respiratory, thoracic and mediastinal disorders - Other, RHINORRHEA 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Sore throat 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Wheezing 1/6 (16.7%) 1/6 (16.7%) 0/14 (0%)
    Skin and subcutaneous tissue disorders
    Alopecia 2/6 (33.3%) 0/6 (0%) 5/14 (35.7%)
    Body odor 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Bullous dermatitis 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Dry skin 0/6 (0%) 0/6 (0%) 2/14 (14.3%)
    Hyperhidrosis 0/6 (0%) 1/6 (16.7%) 1/14 (7.1%)
    Nail discoloration 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Pruritus 1/6 (16.7%) 0/6 (0%) 1/14 (7.1%)
    Rash acneiform 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Rash maculo-papular 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Skin and subcutaneous tissue disorders - Other, FACIAL SORES 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Skin and subcutaneous tissue disorders - Other, FISTULA - SUPERIOR LATERAL STUMP WOUND 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Skin and subcutaneous tissue disorders - Other, MOTTLING OF FINGERS 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Skin and subcutaneous tissue disorders - Other, SEBORRHEIC DERMATITIS 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Skin and subcutaneous tissue disorders - Other, Skin breakdown 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Skin hyperpigmentation 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Vascular disorders
    Flushing 1/6 (16.7%) 2/6 (33.3%) 0/14 (0%)
    Hot flashes 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Hypertension 4/6 (66.7%) 2/6 (33.3%) 1/14 (7.1%)
    Hypotension 1/6 (16.7%) 2/6 (33.3%) 3/14 (21.4%)
    Thromboembolic event 0/6 (0%) 0/6 (0%) 2/14 (14.3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Must obtain prior sponsor approval

    Results Point of Contact

    Name/Title Results Reporting Coordinator
    Organization Children's Oncology Group
    Phone 626-447-0064
    Email resultsreportingcoordinator@childrensoncologygroup.org
    Responsible Party:
    Children's Oncology Group
    ClinicalTrials.gov Identifier:
    NCT03320330
    Other Study ID Numbers:
    • ADVL1614
    • NCI-2017-01103
    • ADVL1614
    • ADVL1614
    • UM1CA097452
    First Posted:
    Oct 25, 2017
    Last Update Posted:
    Apr 26, 2022
    Last Verified:
    Apr 1, 2022