VX15/2503 in Treating Younger Patients With Recurrent, Relapsed, or Refractory Solid Tumors

Status: Recruiting
DFCI Protocol ID: 18-704

This phase I/II trial studies the side effects and best dose of anti-SEMA4D monoclonal antibody VX15/2503 (VX15/2503) 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. Monoclonal antibodies, such as VX15/2503, may interfere with the ability of tumor cells to grow and spread.

Conducting Institutions:

Children's Hospital Boston, Dana-Farber Cancer Institute

Overall PI:

Steven Dubois MD, Dana Farber Cancer Institute

Site-responsible Investigators:


Dana-Farber Cancer Institute: Childrens Hospital Pediatric Clinical Translation Investigation Program CTIP, ctip@partners.org

Eligibility Criteria

Inclusion Criteria:

  -  Parts 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

  -  Parts 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

    -  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)

  -  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) >= 70ml/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

  -  Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
     U/L; for the purpose of this study, the ULN for SGPT is 45 U/L

  -  Serum albumin >= 2 g/dL

  -  Pulse oximetry > 94% on room air if there is clinical indication for determination
     (e.g. dyspnea at rest)

  -  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 an effective
     contraceptive method for the duration of study therapy

  -  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

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