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Study of the TEM-1 Antibody, MORAb-004 (IND# 103821), in Children With Recurrent or Refractory Solid Tumors


Phase 1
13 Months
21 Years
Not Enrolling
Both
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

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Trial Information

Study of the TEM-1 Antibody, MORAb-004 (IND# 103821), in Children With Recurrent or Refractory Solid Tumors


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 change in plasma tumor endothelial marker-1 (TEM-1) levels as well as
circulating proteins involved in the platelet-derived growth factor (PDGF) receptor
signaling pathway as potential biomarkers of MORAb-004 activity.

III. To correlate baseline expression of TEM-1 and proteins involved in the PDGF receptor
signaling pathway in tumor samples 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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

Up to 4 weeks

Safety Issue:

Yes

Principal Investigator

Robin Norris

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group

Authority:

United States: Institutional Review Board

Study ID:

ADVL1213

NCT ID:

NCT01748721

Start Date:

March 2013

Completion Date:

June 2015

Related Keywords:

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

Name

Location

Children's Oncology GroupArcadia, California  91006-3776