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MORAb-004 in Treating Young Patients With Recurrent or Refractory Solid Tumors or Lymphoma

This study has been completed.
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Children's Oncology Group
Information provided by (Responsible Party):
Morphotek
ClinicalTrials.gov Identifier:
NCT01748721
First received: December 11, 2012
Last updated: January 7, 2016
Last verified: December 2015
  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

Condition Intervention Phase
Adult Nasal Type Extranodal NK/T-cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Childhood Burkitt Lymphoma Childhood Diffuse Large Cell Lymphoma Childhood Immunoblastic Large Cell Lymphoma Childhood Nasal Type Extranodal NK/T-cell Lymphoma Cutaneous B-cell Non-Hodgkin Lymphoma Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Hepatosplenic T-cell Lymphoma Intraocular Lymphoma Nodal Marginal Zone B-cell Lymphoma Noncutaneous Extranodal Lymphoma Peripheral T-cell Lymphoma Post-transplant Lymphoproliferative Disorder Recurrent Adult Burkitt Lymphoma Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Adult Diffuse Mixed Cell Lymphoma Recurrent Adult Diffuse Small Cleaved Cell Lymphoma Recurrent Adult Grade III Lymphomatoid Granulomatosis Recurrent Adult Hodgkin Lymphoma Recurrent Adult Immunoblastic Large Cell Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Adult T-cell Leukemia/Lymphoma Recurrent Childhood Anaplastic Large Cell Lymphoma Recurrent Childhood Grade III Lymphomatoid Granulomatosis Recurrent Childhood Large Cell Lymphoma Recurrent Childhood Lymphoblastic Lymphoma Recurrent Childhood Small Noncleaved Cell Lymphoma Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Mycosis Fungoides/Sezary Syndrome Recurrent Small Lymphocytic Lymphoma Recurrent/Refractory Childhood Hodgkin Lymphoma Refractory Hairy Cell Leukemia Small Intestine Lymphoma Splenic Marginal Zone Lymphoma T-cell Large Granular Lymphocyte Leukemia Testicular Lymphoma Unspecified Adult Solid Tumor, Protocol Specific Unspecified Childhood Solid Tumor, Protocol Specific Waldenström Macroglobulinemia Biological: anti-endosialin/TEM1 monoclonal antibody MORAb-004 Other: pharmacological study Other: laboratory biomarker analysis Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Study of the TEM-1 Antibody, MORAb-004 (IND# 103821), in Children With Recurrent or Refractory Solid Tumors

Resource links provided by NLM:


Further study details as provided by Morphotek:

Primary Outcome Measures:
  • MTD, defined as the maximum dose at which fewer than one-third of patients experience dose-limiting toxicities (DLT) graded according to the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 4 weeks ]
  • Incidence of toxicities, graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 3 years ]
    A descriptive summary of all toxicities will be reported.


Enrollment: 27
Study Start Date: November 2013
Study Completion Date: May 2015
Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (MORAb-004)
Patients receive anti-endosialin/TEM1 monoclonal antibody MORAb-004 IV on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
Biological: anti-endosialin/TEM1 monoclonal antibody MORAb-004
Given IV
Other Name: MORAb-004
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Optional correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose of MORAb-004 (anti-endosialin/TEM1 monoclonal antibody MORAb-004) administered as an intravenous infusion every week to children with refractory solid tumors.

II. To define and describe the toxicities of MORAb-004 administered on this schedule.

III. To characterize the pharmacokinetics of MORAb-004 in children with refractory cancer.

IV. To monitor for the development of human anti-human antibody (HAHA) in children receiving MORAb-004.

SECONDARY OBJECTIVES:

I. To preliminarily define the antitumor activity of MORAb-004 within the confines of a phase 1 study.

II. To examine tumor endothelial marker-1 (TEM-1) and PDGFRB levels in tissue and plasma samples as potential biomarkers of MORAb-004 activity.

III. To correlate baseline expression of TEM-1 and PDGFRB (in issue and plasma)with clinical parameters including disease response in an exploratory manner.

OUTLINE: This is a dose escalation study.

Patients receive anti-endosialin/TEM1 monoclonal antibody MORAb-004 intravenously (IV) on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

  Eligibility

Ages Eligible for Study:   13 Months to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • Tissue blocks or slides must be sent per Section 8.5. 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
  • 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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01748721

  Show 20 Study Locations
Sponsors and Collaborators
Morphotek
National Cancer Institute (NCI)
Children's Oncology Group
Investigators
Principal Investigator: Robin Norris Children's Oncology Group
  More Information

Responsible Party: Morphotek
ClinicalTrials.gov Identifier: NCT01748721     History of Changes
Other Study ID Numbers: ADVL1213
NCI-2012-01702 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
U01CA097452 ( U.S. NIH Grant/Contract )
Study First Received: December 11, 2012
Last Updated: January 7, 2016

Additional relevant MeSH terms:
Lymphoma
Leukemia
Neoplasms
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Hodgkin Disease
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Leukemia, Lymphocytic, Chronic, B-Cell
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma, Large B-Cell, Diffuse
Burkitt Lymphoma
Lymphoma, T-Cell
Lymphoma, Large-Cell, Immunoblastic
Plasmablastic Lymphoma
Mycoses
Mycosis Fungoides
Sezary Syndrome
Lymphoma, T-Cell, Cutaneous
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Waldenstrom Macroglobulinemia
Lymphoma, Large-Cell, Anaplastic
Lymphoma, T-Cell, Peripheral
Leukemia, Hairy Cell
Lymphomatoid Granulomatosis
Lymphoma, Extranodal NK-T-Cell
Lymphoproliferative Disorders
Immunoblastic Lymphadenopathy

ClinicalTrials.gov processed this record on September 19, 2017