Phase I Study of MEDI-507 to Treat Lymphoproliferative Disease

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00071825
First received: October 31, 2003
Last updated: August 12, 2014
Last verified: July 2014
  Purpose

This study will determine how much MEDI-507 can be safely given to people with lymphoproliferative diseases - certain cancers that affect infection-fighting white blood cells called T cells. In most cancers that affect T cells, the cells have a protein on their surface called CD2. MEDI-507 is a genetically engineered antibody that targets CD2. In laboratory studies, MEDI-507 has shown some effect in animals with T-cell cancer.

Patients 18 years of age and older with adult T-cell leukemia/lymphoma, cutaneous T-cell lymphoma, peripheral T-cell lymphoma, or large granular lymphocyte leukemia who have CD2 protein on their T cells may be eligible for this study. Patients (except for those with adult T-cell leukemia/lymphoma) must have had prior treatment with chemotherapy, radiation therapy, or antibodies. Candidates are screened with a medical history and physical examination, blood and urine tests, electrocardiogram, x-rays and other imaging studies, photographs of skin lesions, if any, a skin biopsy (removal of a small piece of tissue) of suspicious lesions, and lymph node biopsy, if the node is accessible by a fine needle.

Patients are enrolled into one of seven groups, with three patients per group. Subsequent groups of patients receive a higher dose of MEDI-507 than the previous one as long as the drug continues to be safe and well tolerated. The first group of patients receives 0.2 milligrams mg/kg of the drug for 2 consecutive days every other week for 16 weeks. The next three patients entering the study receive the same dose for 3 consecutive days every other week. Subsequent groups receive higher doses of the antibody. Patients are hospitalized on the days they receive the antibody.

In addition to MEDI-507 treatment, patients may receive additional therapies as follows:

  • Diphenhydramine (Benadryl ) and acetominophen (Tylenol ) to reduce allergic reactions to MEDI-507.
  • Blood transfusions to maintain sufficient levels of blood cells and platelets.
  • Filgrastim, a drug that stimulates production of white blood cells, to improve white cell counts.
  • Allopurinol, a drug that helps help prevent tumor lysis syndrome. Cancer treatment may sometimes result in this condition, which upsets the way the body gets rid of certain chemicals in the blood. Allopurinol is taken by mouth for 5 days starting 1 day before each MEDI-507 infusion.
  • Anti-infective agents, such as fluconazole, valacyclovir, trimethoprim-sulfamethoxazole, and others as needed to prevent bacterial, viral, or fungal infections.

After patients complete the 16-week course of treatment, they return to the clinic for follow-up examinations 30 days after the last drug dose and then every 3 months for 1 year.


Condition Intervention Phase
Lymphoproliferative Disorders
Drug: MEDI-507
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase I Trial of Medi-507 in CD2-Positive Lymphoproliferative Disease

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Enrollment: 29
Study Start Date: October 2003
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: MEDI-507
    N/A
Detailed Description:

Background:

  • Monclonal antibodies have significant therapeutic benefit in patients with cancer.
  • MEDI-507 is an IgG1 humanized monoclonal antibody directed at CD2 which is highly expressed on malignant T and NK cells.
  • NOD/SCID mice bearing CD2 positive MET-1 adult T-cell leukemia/lymphoma survive tumor challenge and have a survival equivalent to that of non-tumor bearing animals when treated with weekly doses of MEDI-507.

Objectives:

  • Determine the maximum tolerated dose (MTD), safety and tolerability of MEDI-507 in patients with CD2-positive lymphoproliferative disorders.
  • Evaluate the serum pharmacokinetics of MEDI-507 and determine the dose of MEDI-507 required to saturate CD2-binding sites in lymph nodes and peripheral blood.
  • Assess the clinical tumor response in a preliminary fashion in a variety of CD2-positive lymphoproliferative disorders.

Eligibility:

-Patients with CD2 positive lymphoproliferative disease including untreated patients with adult T-cell leukemia/lymphoma; patients with large granular lymphocyte leukemia, peripheral T-cell lymphoma and cutaneous T-cell lymphoma who have progressive disease after standard therapy.

Design:

  • Cohorts of patients will be treated with escalating doses of MEDI-507 ranging from 0.4 to 15 mg/kg.
  • Tumor response will be evaluated on a monthly basis during treatment.
  • Tumor aspirates will be obtained before and after treatment to determine the effect of MEDI-507 on CD2 expression.
  • The time course of T and NK cell depletion and recovery will be monitored.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Patients must meet all of the following criteria at the time of enrollment.

  1. Men or women at least 18 years of age. Women of childbearing potential must have a negative serum pregnancy test within 5 days of the initial MEDI-507 administration and a negative urine pregnancy test on Day 0 prior to receiving the first dose of MEDI-507. Women of childbearing potential must agree to practice an effective method of contraception. Sexually active males must agree to use a condom.
  2. Histologically confirmed diagnosis of a lymphoproliferative disorder as determined by the Laboratory of Pathology at the Clinical Center at the National Institutes of Health (NIH). Only patients with the following lymphoproliferative disorders will be eligible.

    1. ATL: Patients with all except the smoldering form of adult T-cell leukemia/lymphoma (ATL) will be eligible, regardless of whether they have had previous therapy since there is no effective standard of care therapy for this disease.
    2. CTCL: Patients with all stages of cutaneous T-cell lymphoma (CTCL) are eligible with the exception of Stage Ia. Patients with Stages Ib through III are eligible if their disease has failed at least one standard form of prior therapy.
    3. PTCL: Patients with Stages I-IV peripheral T-cell lymphoma (PTCL) are eligible if their disease has progressed after standard chemotherapy.
    4. LGL: Patients with large granular lymphocyte leukemia must have myelosuppression (granulocyte count less than or equal to1,500/microL, platelet count less than or equal 75,000/microL, or hemoglobin less than or equal 10 g/dL), or require hematopoietic support (transfusion or colony stimulating factors including filgrastim, IL-11, or erythropoietin) to maintain counts at these or higher levels or systemic symptoms (fever, night sweats or weight loss). Patients must have disease that is unresponsive to one prior therapy. Patients with monoclonal and polyclonal forms of the disease will be eligible.
  3. Cells must express CD2. CD2 expression will be verified by immunohistochemistry in the Laboratory of Pathology at the NIH. At least 30% of tumor cells must be CD2 positive for the patient to be eligible for the study by immunohistochemistry. CD2 staining will be performed on existing tissue blocks and on fresh tumor tissue if a biopsy is performed. It is expected that the majority of patients will have CD2 expression evaluated by flow cytometry and the majority of cells will express the marker.
  4. Measurable or evaluable disease.
  5. Karnofsky Performance Status greater than or equal to 70%.
  6. Life expectancy of greater than 2 months.
  7. Granulocyte count greater than or equal to 1,000/mm3 and a platelet count greater than or equal to 50,000/mm3. Patients with LGL leukemia are excluded from these criteria. For patients with LGL leukemia, ANC and platelet count will not be considered in determining study eligibility.
  8. Serum creatinine less than or equal to 1.5 mg/dL or 24 hour measured creatinine clearance greater than 60 ml/min.
  9. Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) value less than or equal to 2.0-fold greater than the upper limit of normal (if due to lymphoma in the liver, patients will be allowed to have transaminase values less than or equal to 5.0-fold greater than the upper limit of normal) and bilirubin less than or equal to 2.0 mg/dL unless due to Gilbert's syndrome (unconjugated hyperbilirubinemia) in which case the bilirubin should be less than or equal to 3.5 mg/dL.
  10. Prior treatment with cytotoxic chemotherapy, surgery, and prolonged cytolytic steroid therapy is allowed provided last treatment was given at least 3 weeks prior to first dose of study drug administration and all toxicities have resolved.
  11. Prior treatment with other investigational anticancer drugs and monoclonal antibodies is allowed provided the last treatment was given at least 30 days prior to the first dose of study drug administration.
  12. Patients must understand and sign an NCI pre-screening consent form and a protocol specific informed consent form prior to receipt of any study medication or beginning study procedures.

EXCLUSION CRITERIA:

Patients must have none of the following at the time of enrollment.

  1. Known history of central nervous system (CNS) disease.
  2. Pregnant or nursing. The effects of MEDI-507 on the developing fetus and the nursing infant are unknown.
  3. Positive for human immunodeficiency virus (HIV) because of the risk of increased HIV-associated complications due to increased immunosuppression.
  4. Positive for hepatitis B surface antigen or with antibodies to hepatitis C virus because the therapy may be associated with increased viral replication.
  5. CMV disease or clinically significant CMV antigenemia (determined by prevailing guidelines).
  6. Prior treatment with MEDI-507.
  7. Prior history of significant adverse events related to previously administered monoclonal antibody.
  8. History within 6 months prior to first dose of study drug administration or evidence of intercurrent illnesses including myocardial infarction, uncontrolled hypertension, stroke, or transient ischemic attacks.
  9. Respiratory insufficiency requiring oxygen therapy or O2 saturation less than 90% by pulse oximetry.
  10. Active infection requiring systemic anti-infective therapy or other physical or psychological illnesses that would increase risk to the patient in the opinion of the Principal Investigator.
  11. Any general medical, psychological, or behavioral conditions that in the opinion of the investigator may pose additional risk in administering study drug to the patient or will not permit the patient to complete the study or sign informed consent.
  12. Hypogammaglobulemia (LGL patients only).
  13. Diagnosis of NK-cell LGL.
  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: NCT00071825

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Thomas A Waldmann, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00071825     History of Changes
Obsolete Identifiers: NCT00075361
Other Study ID Numbers: 040031, 04-C-0031
Study First Received: October 31, 2003
Last Updated: August 12, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Mycosis Fungoides
Adult T-Cell Lymphoma
Peripheral Lymphoma
Monoclonal Antibody
Large Granular Lymphocyte
Lymphoproliferative Disease

Additional relevant MeSH terms:
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on September 30, 2014