Clinical Trials

ADVL1213: A Phase I Study of the TEM-1 Antibody, MORAb-004, in Children with Recurrent or Refractory Solid Tumors

What is the purpose of this study?

PURPOSE: 

This phase I trial studies the side effects and best dose of MORAb-004 in treating young patients with recurrent or refractory solid tumors or lymphoma. Monoclonal antibodies, such as MORAb-004, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them.

Study Type:  Interventional
Masking: Open Label
Primary Purpose: Treatment

Who can participate?

AGES ELIGIBLE FOR STUDY:  13 Months to 21 Years

Criteria

Inclusion Criteria:

  • Patients with relapsed or refractory solid tumors or lymphoma, excluding central nervous system (CNS) tumors, are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse; (patients with primary CNS tumors, known CNS metastases, or a prior history of CNS metastases are not eligible)
  • Patients must have either measurable or evaluable 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; Note: 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 chemotherapy
  • At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
  • At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) 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
  • At least 7 days after the last dose of a biologic agent; 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
  • At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
  • At least 3 half-lives of the antibody after the last dose of a monoclonal antibody
  • At least 14 days after local palliative radiotherapy (XRT) (small port); at least 150 days must have elapsed if prior total-body irradiation (TBI), craniospinal XRT or if >= 50% radiation of pelvis; at least 42 days must have elapsed if other substantial bone marrow (BM) radiation
  • No evidence of active graft vs. host disease and at least 56 days must have elapsed after transplant or stem cell infusion
  • For patients with solid tumors without known bone marrow involvement:
  • 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) For patients with known bone marrow metastatic disease:
  • ANC >= 750/mm^3
  • Platelet count >= 75,000/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 not be evaluable for hematologic toxicity; these patients must not be known to be refractory to red cell or platelet transfusion; at least 5 of every cohort of 6 patients with a solid tumor or lymphoma must be evaluable for hematologic toxicity; 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:
  • =< 0.6 mg/dL for patients age 1 to < 2 years
  • =< 0.8 mg/dL for patients age 2 to < 6 years
  • =< 1 mg/dL for patients age 6 to 10 2 years
  • =< 1.2 mg/dL for patients age 10 to < 13 years
  • =< 1.4 mg/dL for female patients age >= 13 years
  • =< 1.5 mg/dL for male patients age 13 to < 16 years
  • =< 1.7 mg/dL for male patients age >= 16 years
  • Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L
  • Serum albumin >= 2 g/dL
  • Activated partial thromboplastin time (aPTT) and prothrombin time (PT) =< 1.5 x ULN
  • 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

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
  • Patients receiving chronic systemic corticosteroids are not eligible
  • Patients who are currently receiving another investigation drug are not eligible
  • Patients who are currently receiving other anti-cancer agents are not eligible
  • 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 known human immunodeficiency virus (HIV), viral hepatitis, or an uncontrolled infection are not eligible
  • Patients with primary CNS tumors are excluded
  • Patients with prior history of or known metastatic CNS disease involvement are excluded; (Note: CNS imaging for patients without a known history of
  • CNS disease is only required if clinically indicated)
  • Patients who have had or are planning to have the following invasive procedures are not eligible:
  • Major surgical procedure, laparoscopic procedure, open biopsy or significant traumatic injury within 28 days prior to enrollment
  • Central line placement or subcutaneous port placement is not considered major surgery but must be placed at least 3 days prior to enrollment for external lines (e.g. Hickman or Broviac) and at least 7 days prior to enrollment for subcutaneous port
  • Core biopsy within 7 days prior to enrollment
  • Fine needle aspirate within 7 days prior to enrollment
  • Patients who have received 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
  • Patients with a history of grade >= 2 allergic reaction to a prior monoclonal antibody therapy are not eligible; patients who have experienced an anaphylactic reaction to a prior monoclonal antibody are not eligible
  • Patients with history of clinically significant bleeding risk (including evidence of active bleeding: intratumoral hemorrhage by current imaging, or bleeding diathesis; bleeding/coagulation disorder; active fracture; non-healing wound; and active gastric ulcer) are not eligible

Ages

  • From 1 To 21  years old

Conditions

  • Cancer - Leukemia and Lymphoma
  • Cancer - Liver Tumors
  • Cancer - Musculoskeletal Tumors
  • Cancer - Neuroblastoma
  • Cancer - Neurofibromatosis Tumors
  • Cancer - Retinoblastoma

Who should I contact for more information?

For more information contact:

Cincinnati Children’s Hospital Medical Center
Division of Hematology/Oncology
3333 Burnet Ave., Cincinnati, OH 45229-3039

Phone: 513-636-2799

cancer@cchmc.org


Where can I find additional information?