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Anti-Tac(90 Y-HAT) to Treat Hodgkin's Disease, Non-Hodgkin's Lymphoma and Lymphoid Leukemia

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ClinicalTrials.gov Identifier: NCT00001575
Recruitment Status : Completed
First Posted : November 4, 1999
Results First Posted : December 7, 2015
Last Update Posted : December 7, 2015
Sponsor:
Information provided by (Responsible Party):
Thomas Waldmann, M.D., National Institutes of Health Clinical Center (CC)

Tracking Information
First Submitted Date  ICMJE November 3, 1999
First Posted Date  ICMJE November 4, 1999
Results First Submitted Date  ICMJE May 14, 2015
Results First Posted Date  ICMJE December 7, 2015
Last Update Posted Date December 7, 2015
Study Start Date  ICMJE April 1997
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 30, 2015)
  • Maximum Tolerated Dose (MTD) of 90Y-HAT [ Time Frame: Patients could receive 90Y-HAT 15mCi per cycle and complete up to a maximum of 7 doses or 2 doses by the average of every 6 weeks. ]
    Phase I portion maximum tolerated dose (MTD) is defined as the dose level below the dose at which 2 out of 2-6 patients develop DLT (if any patient develops grade IV toxicity of any type (excluding grade IV neutropenia) or grade III non-hematologic toxicity that patient may not continue on the study at the same dose level and therefore has had a dose limiting toxicity). There can be no more than 1 out of 6 patients with DLT at the MTD. The MTD will be assessed using only the results from the first cycle of therapy.
  • Clinical Response [ Time Frame: Patient would be measured with computed tomography (CT) scan, Fludeoxyglucose (18F) positron-emission tomography (FDG PET) scan in 28 days before treatment. Patient would be evaluated with In-HAT imaging at Day 1,4,5,6 and Day 7 in week 1 of each cycle. ]
    Clinical Response of patient is measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Tumor responses were evaluated by In-HAT imaging (i.e., simultaneous with administration of therapeutic 90Y-daclizumab), Fludeoxyglucose (18F) positron-emission tomography (FDG PET) scans and computed tomography (CT) scans. Complete response is a disappearance of all measurable and evaluable disease lasting more than I month. Partial response is a reduction by ≥ 50% of leukemic cell count or ≥ 50% reduction in the size of all measurable lesions, and no increase in size of any measurable or evaluable lesion or appearance of new lesions for 1 month. Stable disease is less than partial response with no more than a 25% increase in leukemic cell count, no new lesions, or less than a 25% increase in any measurable lesion. Progressive disease is at least a 25% increase in leukemic cell count, appearance of new lesions, or an increase of 25% or greater in any measurable lesion after 2 weeks.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 30, 2015)
Number of Participants With Adverse Events [ Time Frame: 16 yrs 18 days ]
Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Anti-Tac(90 Y-HAT) to Treat Hodgkin's Disease, Non-Hodgkin's Lymphoma and Lymphoid Leukemia
Official Title  ICMJE Not Provided
Brief Summary

This study will examine the use of a radioactive monoclonal antibody called yttrium 90-labeled humanized anti-Tac (90 Y-HAT) for treating certain cancers. Monoclonal antibodies are genetically engineered proteins made in large quantities and directed against a specific target in the body. The anti-Tac antibody in this study is targeted to tumor cells and is tagged (labeled) with a radioactive substance called Yttrium-90 (Y-90). The study will determine the maximum tolerated dose of 90Y-HAT and examine its safety and effectiveness.

Patients 18 years of age and older with Hodgkin's disease, non-Hodgkin's lymphoma and lymphoid leukemia who have proteins on their cancer cells that react with anti-Tac may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, electrocardiogram (EKG), chest x-ray, computed tomography (CT) scan or ultrasound of the abdomen, positron emission tomography (PET) scan of the neck and body, and skin test for immune reactivity to antigens (similar to skin tuberculin test).

Before beginning treatment, participants may undergo additional procedures, including the following:

  • Patients with suspicious skin lesions have a skin biopsy. An area of skin is numbed and a circular piece of skin about 1/4-inch diameter is removed with a cookie cutter-like instrument.
  • Patients with hearing loss have a hearing test.
  • Patients with neurological symptoms have a lumbar puncture (spinal tap). A local anesthetic is given and a needle is inserted in the space between the bones in the lower back where the cerebrospinal fluid circulates below the spinal cord. A small amount of fluid is collected through the needle.
  • Patients who have not had a bone marrow biopsy within 6 months of screening also undergo this procedure. The skin and bone at the back of the hip are numbed with a local anesthetic and a small piece of bone is withdrawn through a needle.

Patients receive 90 Y-HAT in escalating doses to determine the highest dose that can be safely given. The first group of three patients receives a low dose and, if there are no significant side effects at that dose, the next three patients receive a higher dose. This continues with subsequent groups until the maximum study dose is reached. 90 Y-HAT is given through a vein (intravenous (IV)) over a 2-hour period. In addition, a drug called Pentetate Calcium Trisodium Inj (Ca-DTPA) is given via IV over 5 hours for 3 days to help reduce the side effects of the 90Y-HAT. In some patients, the 90 Y-HAT may also be attached to a radioactive metal called Indium-111 to monitor what happens to the injected material. During infusion of the drug, patients undergo PET scanning to trace the path of the injected material in the body. For this procedure, the patient lies in the scanner, remaining in one position during the entire infusion.

Blood and urine specimens are collected periodically over a 6-week period following the infusion to determine the level of the radioactive antibody. Bone marrow, lymph node, or skin biopsies may be done to determine how much of the antibody entered these sites. Patients whose disease remains stable or improves with therapy may receive up to six more infusions of 90 Y-HAT, with at least a 6-week interval between treatments.

Detailed Description

Background:

Cluster of differentiation 25 (CD25) is expressed on the malignant cells of patients with certain lymphoid malignancies as well as the non-malignant T cells that surround the malignant tumor cells of patients with Hodgkin's disease.

Zenapax is a humanized monoclonal antibody that binds to CD25.

Zenapax has been chemically modified by the addition of a chelating molecule to permit binding of radioactive yttrium.

The yttrium labeled Zenapax binds to CD25 to deliver radiation treatment to the tumor.

Objective:

To assess the toxicity and therapeutic efficacy of (90)Yttrium-labeled humanized anti-Tac((90)Y-HAT) in patients with Tac-expressing hematologic malignancies.

To determine the sites of localization of radiolabeled Zenapax.

Eligibility:

Patients with Hodgkin's disease and other CD25 positive lymphoid malignancies.

The patient must have a granulocyte of at least 1,200/mm^3 and a platelet count of greater than 100,000/mm^3.

Design:

Patients will be treated with 10 mCi (if a bone marrow transplant was part of the patient's previous therapy) or 15 mCi of yttrium labeled Zenapax.

Indium labeled Zenapax is given to demonstrate the antibody distribution and confirm localization at sites of tumor.

Treatment is given every six weeks if tolerated and patients will be hospitalized for about one week for each treatment.

Tumor response will be evaluated after every treatment. Stable or responding patients will continue treatment with evaluations after every cycle of treatment. Patients will be treated for up to seven cycles.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hodgkin's Disease
  • Lymphoma, Non-Hodgkin
Intervention  ICMJE
  • Biological: Y-90 Humanized Anti-Tac
    10 mCi (if a bone marrow transplant was part of the patient's previous therapy) or 15 mCi of yttrium labeled anti-TAC; followed by calcium trisodium Inj (Ca DTPA).
  • Drug: Calcium-DTPA
    Ca-DTPA will be administered intravenously on Days 1-3 to clear the radioactive agent from the body
Study Arms  ICMJE Experimental: Anti-Tac yttrium 90-labeled humanized anti-Tac (90 Y-HAT)

10 mCi (if a bone marrow transplant was part of the patient's previous therapy) or 15 mCi of yttrium labeled anti-TAC; followed by calcium trisodium Inj (Ca DTPA).

Ca-DTPA will be administered intravenously on Days 1-3 to clear the radioactive agent from the body

Interventions:
  • Biological: Y-90 Humanized Anti-Tac
  • Drug: Calcium-DTPA
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 20, 2014)
87
Original Enrollment  ICMJE
 (submitted: June 23, 2005)
90
Actual Study Completion Date  ICMJE November 2013
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • INCLUSION CRITERIA:

All patients must have a histologically confirmed diagnosis of Hodgkin's disease. Patients who have had an allogeneic or autologous transplant are eligible if they are more than 100 days post-transplant.

At least 10% of each patient's malignant cells from peripheral blood, lymph node, skin, or other extranodal sites must react with anti-Tac, as determined by immunofluorescent or immunoperoxidase staining. Because of the high incidence of Tac positivity in infiltrating T cells in Hodgkin's disease, patients with cluster of differentiation 25 (CD25) positive infiltrating T cells will be eligible even if the Hodgkin's cells are negative.

Diagnoses and Stage Disease: 1) Non-Hodgkin's Lymphoma (NHL): Patients with all histopathologic subtypes of Tac-expressing NHL are eligible. Patients with indolent NHL Stages II through IV are eligible if they have failed at least one standard therapy and have disease requiring treatment. Patients with aggressive NHL are eligible if they have relapse after standard chemotherapy and either are not eligible for or have refused salvage chemotherapy or bone marrow transplantation.

2) Hodgkin's disease: Patients who are considered to have a low potential for cure with conventional chemotherapy or radiation therapy are eligible. Specifically, patients with stages II-IV Hodgkin's disease are eligible if they have relapsed or failed to attain a complete remission after first-line chemotherapy and either are not eligible for or have refused salvage chemotherapy or bone marrow transplantation.

3) Cutaneous T-cell Lymphoma (CTCL): Patients with all stages of Tac-expressing CTCL are eligible with the exception of Stage Ia. Patients with Stages Ib through III are eligible if they have failed at least one standard therapy. Patients with stage IV are eligible regardless of whether they have had previous therapy.

4) Peripheral T-cell Lymphoma (PTCL): Patients with stages I - IV PTCL are eligible if they have relapsed after first-line chemotherapy and either are not eligible for or have refused salvage chemotherapy or bone marrow transplantation.

Other: Patients with lymphoid leukemias or lymphomas not easily classified in the above categories will be eligible providing they have failed standard therapy and are not eligible for or have refused bone marrow transplantation.

Patients must have a Karnofsky performance status of at least 50.

Patients must have a creatinine of less than 2.0 mg/dl. If they patient has an abnormally elevated creatinine a creatinine clearance must be greater than 50 ml/min.

Patients must have serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) less than 5 times the upper limit of normal, bilirubin less than 3.0 unless this is felt to be due to the malignancy.

Patients must not have clinical cardiac failure. Patients with symptomatic pulmonary dysfunction are eligible only if it is due to the underlying malignancy.

The patient must have a granulocyte count of at least 1,200/mm^3 and a platelet count of greater than 100,000/mm^3.

Patients must be able to understand and sign informed consent.

Breast-feeding females are not eligible for the study.

Omission of cytotoxic chemotherapy or other systemic therapy of the malignancy for 3 weeks prior to entry into trial. However, patients receiving corticosteroids will not be excluded. Patients receiving corticosteroids must be on a stable dose for at least three weeks before receiving yttrium 90-labeled humanized anti-Tac (90Y-HAT) on this study.

Patients must have a life expectancy of greater than 1 month.

Patients must be at least 18 years old.

EXCLUSION CRITERIA:

Female patients of child bearing potential will be tested for pregnancy; pregnant patients will be excluded from the study.

Patients who are human immunodeficiency virus (HIV) antibody positive.

Patients with symptomatic disease that is due to malignant involvement of the central nervous system.

Patients with active second primary cancer.

Patients receiving chronic anticoagulant therapy will be excluded from the study.

Patients requiring urgent chemotherapy or radiation therapy for management of their malignancy will be excluded.

Patients with evidence of myelodysplastic syndrome or chromosomal abnormalities in their screening bone marrow evaluation

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00001575
Other Study ID Numbers  ICMJE 970110
97-C-0110
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Thomas Waldmann, M.D., National Institutes of Health Clinical Center (CC)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Thomas A Waldmann, M.D. National Cancer Institute (NCI)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP