NeoplasmsPhase 1NCT00048880
Phase I Study of HeFi-1 to Treat Cancers With CD30 Protein
A Phase 1 study testing HeFi-1 Monoclonal Antibody in people with Neoplasms, run by National Cancer Institute (NCI) at 2 sites in United States.
Trial summary
Background: Some cancers, such as Hodgkin's disease, anaplastic large cell lymphoma and others, have a protein on the surface of the cancer cell called CD30. HeFi-1 is an antibody that binds to the CD30 protein and sends signals to the cancer cells that can cause them to die. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- HeFi-1 Monoclonal Antibody
- How many people
- 9 participants
- Where
- 2 sitesUnited States
- Study dates
- 5 Nov 2002to 2 Jul 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All Patients must have a histologically confirmed diagnosis of malignancy by department of pathology at the enrolling institution.
- Tumor cells must express CD30. CD30 expression will be verified by immunohistochemistry. At least 30% of tumor cells must be CD30 positive. CD30 staining will be performed on existing tissue blocks and on fresh tumor tissue if a biopsy is performed.
- Patients must have measurable or evaluable disease.
- The patient must have a granulocyte count of at least 1000/mm(3) and a platelet count of 50,000/mm(3) without transfusion.
- Patients must have a creatinine of less than 2.0 mg/dL.
- Omission of cyotoxic chemotherapy and systemic steroids for 3 weeks prior to entry into the trial is required. Topical and inhaled steroids will be permitted.
Show all 11Show fewer
- Patients must have a life expectancy of greater than 2 months.
- Eligible patients must be greater than or equal to 18 years old. There is no upper age limit.
- Patients must have SGOT and SGPT value less than or equal to 2.0-fold greater than the upper limit of normal and bilirubin less than or equal to 2.0 mg/dL.
- Patients must be able to understand and sign an Informed Consent form.
- Karnofsky Performance Status greater than or equal to 70%.
Who cannot join
- Patients with central nervous system disease as assessed by clinical examination. If the clinical findings suggest the presence of CNS disease a lumbar puncture should be done.
- Pregnant and nursing patients are not eligible for the study because the effects of HeFi-1 on the developing fetus and the nursing infant are unknown. All patients must agree to use effective contraceptive measures while receiving therapy and for two weeks afterwards.
- HIV positive patients are excluded from the study because the toxicity may be different in this population.
- Hepatitis B surface antigen positive and Hepatitis C antibody positive patients are excluded because the toxicity of therapy may be different in this population.
- Patients who previously received murine monoclonal antibody therapy are ineligible.
- Patients who are HAMA positive.
- Patients with significant renal, pulmonary, cardiovascular, endocrine, rheumatologic or allergic disease should be excluded.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
About this study
Official title: Phase I Study of HeFi-1 in Refractory CD30-Positive Malignancy
Background:
- Some cancers, such as Hodgkin's disease, anaplastic large cell lymphoma and others, have a protein on the surface of the cancer cell called CD30.
- HeFi-1 is an antibody that binds to the CD30 protein and sends signals to the cancer cells that can cause them to die.
Read more
Objectives:
- To determine the highest dose of HeFi-1 that can safely be given to patients with tumors that have the CD30 protein.
- To determine the response of the tumor to treatment with HeFi-1.
Eligibility:
- Patients 18 years of age and older with Hodgkin's disease, anaplastic large cell lymphoma, cutaneous T cell lymphoma and adult T cell leukemia or lymphoma who have signs of tumor growth or recurrence following standard treatment
- Patients' tumor cells must have the CD30 protein.
Design:
- Groups of three patients are treated with increasingly higher doses of HeFi-1 (ranging from 0.5 to 5 mg/kg) to determine the highest safe dose.
- HeFi-1 is infused through a vein on 4 days, followed by 2 days of rest over a 10-day period. Patients may receive up to 2 treatment courses if they show some response and do not have severe side effects.
- Blood samples are collected several times during the study to determine safety. A lymph node biopsy is done at the beginning of the study to test the effect of HeFi-1 on cancer cells in the test tube, and a bone marrow biopsy may be done at the end of treatment if the bone marrow was positive for tumor cells at the beginning of treatment.
Read the detailed description
BACKGROUND:
The scientific basis for this study is the observation that antibodies directed at the ligand-binding site of CD30 induce apoptosis in vitro and cure animals bearing CD30-positive tumors.
HeFi-1, a murine monoclonal antibody developed at the NCI, specifically binds human CD30, a member of the tumor necrosis receptor superfamily, at the ligand-binding site.
CD30 is expressed on activated T-cells, Reed-Sternberg cells, anaplastic large cell lymphoma, and some AIDS-related lymphoma cells.
Tumor cells from patients with anaplastic large cell lymphoma are sensitive to the effects of HeFi-1 but Hodgkin's disease cell lines show variable responsiveness due to the presence of mutations in I B kinase which result in constitutive activation of NF- B.
OBJECTIVE:
The primary objective of this study is to determine the toxicity and maximum tolerated dose of HeFi-1 in patients with CD30-positive malignancy.
This study will explore the pharmacokinetics, dose required to saturate CD30 binding sites in tumor aspirates, and the frequency and time course of onset of development of human anti-mouse antibody (HAMA).
These studies will allow us to monitor in a preliminary fashion the clinical tumor response, measured by reduction in tumor lesions and by following the tumor marker serum soluble interleukin 2 receptor.
ELIGIBILITY:
Patients with measurable or evaluable CD30-positive lymphoma who have become refractory to standard therapy, including Hodgkin's disease, systemic anaplastic large cell lymphoma, cutaneous T cell lymphoma and adult T cell leukemia/lymphoma are eligible for treatment.
DESIGN:
This is a phase I dose-escalation trial in which cohorts of three patients will be treated with HeFi-1 ranging from 0.5 to 5 mg/kg/dose (total dose of 2 to 20 mg/kg per treatment course).
Four doses will be given on an every three days schedule over a 10-day period for each cycle.
Two cycles of therapy will be administered provided the patient has had a partial or complete response and has not developed dose-limiting toxicity or HAMA.
- Conditions
- Neoplasms
- Being tested
- HeFi-1 Monoclonal Antibody
- Keywords
- Anaplastic Large Cell Lymphoma, Monoclonal Antibody, CD30, Antibody Saturation, Apoptosis, Flow Cytometry, Cancer
- Medical subject headings
- Neoplasms, Lymphoma, Large-Cell, Anaplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HeFi-1 Monoclonal AntibodyDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2002 (estimated)
- Study start5 Nov 2002
- Primary completion2 Jul 2008
- Study completion2 Jul 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00048880
- Sponsor's protocol ID
- 030038
- Other IDs
- 03-C-0038
- Status last verified
- 5 Mar 2010
- First submitted
- 8 Nov 2002
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Catane R, Longo DL. Monoclonal antibodies for cancer therapy. Isr J Med Sci. 1988 Sep-Oct;24(9-10):471-6.
PubMed 3060441Grillo-Lopez AJ, White CA, Varns C, Shen D, Wei A, McClure A, Dallaire BK. Overview of the clinical development of rituximab: first monoclonal antibody approved for the treatment of lymphoma. Semin Oncol. 1999 Oct;26(5 Suppl 14):66-73.
PubMed 10561020Shak S. Overview of the trastuzumab (Herceptin) anti-HER2 monoclonal antibody clinical program in HER2-overexpressing metastatic breast cancer. Herceptin Multinational Investigator Study Group. Semin Oncol. 1999 Aug;26(4 Suppl 12):71-7.
PubMed 10482196
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of HeFi-1 in Refractory CD30-Positive Malignancy
- ClinicalTrials.gov ID
- NCT00048880
- Acronym / sponsor ID
- 030038
- Conditions
- Neoplasms
- Keywords
- Anaplastic Large Cell Lymphoma, Monoclonal Antibody, CD30, Antibody Saturation, Apoptosis, Flow Cytometry, Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 5 Nov 2002
- Primary completion
- 2 Jul 2008 (actual)
- Study completion
- 2 Jul 2008 (actual)
- First posted
- 11 Nov 2002 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Some cancers, such as Hodgkin's disease, anaplastic large cell lymphoma and others, have a protein on the surface of the cancer cell called CD30.
- HeFi-1 is an antibody that binds to the CD30 protein and sends signals to the cancer cells that can cause them to die.
Objectives:
- To determine the highest dose of HeFi-1 that can safely be given to patients with tumors that have the CD30 protein.
- To determine the response of the tumor to treatment with HeFi-1.
Eligibility:
- Patients 18 years of age and older with Hodgkin's disease, anaplastic large cell lymphoma, cutaneous T cell lymphoma and adult T cell leukemia or lymphoma who have signs of tumor growth or recurrence following standard treatment
- Patients' tumor cells must have the CD30 protein.
Design:
- Groups of three patients are treated with increasingly higher doses of HeFi-1 (ranging from 0.5 to 5 mg/kg) to determine the highest safe dose.
- HeFi-1 is infused through a vein on 4 days, followed by 2 days of rest over a 10-day period. Patients may receive up to 2 treatment courses if they show some response and do not have severe side effects.
- Blood samples are collected several times during the study to determine safety. A lymph node biopsy is done at the beginning of the study to test the effect of HeFi-1 on cancer cells in the test tube, and a bone marrow biopsy may be done at the end of treatment if the bone marrow was positive for tumor cells at the beginning of treatment.
Detailed description
BACKGROUND:
The scientific basis for this study is the observation that antibodies directed at the ligand-binding site of CD30 induce apoptosis in vitro and cure animals bearing CD30-positive tumors.
HeFi-1, a murine monoclonal antibody developed at the NCI, specifically binds human CD30, a member of the tumor necrosis receptor superfamily, at the ligand-binding site.
CD30 is expressed on activated T-cells, Reed-Sternberg cells, anaplastic large cell lymphoma, and some AIDS-related lymphoma cells.
Tumor cells from patients with anaplastic large cell lymphoma are sensitive to the effects of HeFi-1 but Hodgkin's disease cell lines show variable responsiveness due to the presence of mutations in I B kinase which result in constitutive activation of NF- B.
OBJECTIVE:
The primary objective of this study is to determine the toxicity and maximum tolerated dose of HeFi-1 in patients with CD30-positive malignancy.
This study will explore the pharmacokinetics, dose required to saturate CD30 binding sites in tumor aspirates, and the frequency and time course of onset of development of human anti-mouse antibody (HAMA).
These studies will allow us to monitor in a preliminary fashion the clinical tumor response, measured by reduction in tumor lesions and by following the tumor marker serum soluble interleukin 2 receptor.
ELIGIBILITY:
Patients with measurable or evaluable CD30-positive lymphoma who have become refractory to standard therapy, including Hodgkin's disease, systemic anaplastic large cell lymphoma, cutaneous T cell lymphoma and adult T cell leukemia/lymphoma are eligible for treatment.
DESIGN:
This is a phase I dose-escalation trial in which cohorts of three patients will be treated with HeFi-1 ranging from 0.5 to 5 mg/kg/dose (total dose of 2 to 20 mg/kg per treatment course).
Four doses will be given on an every three days schedule over a 10-day period for each cycle.
Two cycles of therapy will be administered provided the patient has had a partial or complete response and has not developed dose-limiting toxicity or HAMA.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- All Patients must have a histologically confirmed diagnosis of malignancy by department of pathology at the enrolling institution.
- Tumor cells must express CD30. CD30 expression will be verified by immunohistochemistry. At least 30% of tumor cells must be CD30 positive. CD30 staining will be performed on existing tissue blocks and on fresh tumor tissue if a biopsy is performed.
- Patients must have measurable or evaluable disease.
- The patient must have a granulocyte count of at least 1000/mm(3) and a platelet count of 50,000/mm(3) without transfusion.
- Patients must have a creatinine of less than 2.0 mg/dL.
Key exclusion criteria (7 listed)
- Patients with central nervous system disease as assessed by clinical examination. If the clinical findings suggest the presence of CNS disease a lumbar puncture should be done.
- Pregnant and nursing patients are not eligible for the study because the effects of HeFi-1 on the developing fetus and the nursing infant are unknown. All patients must agree to use effective contraceptive measures while receiving therapy and for two weeks afterwards.
- HIV positive patients are excluded from the study because the toxicity may be different in this population.
- Hepatitis B surface antigen positive and Hepatitis C antibody positive patients are excluded because the toxicity of therapy may be different in this population.
- Patients who previously received murine monoclonal antibody therapy are ineligible.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HeFi-1 Monoclonal Antibody | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 3060441Catane R, Longo DL. Monoclonal antibodies for cancer therapy. Isr J Med Sci. 1988 Sep-Oct;24(9-10):471-6.
- Background: PubMed 10561020Grillo-Lopez AJ, White CA, Varns C, Shen D, Wei A, McClure A, Dallaire BK. Overview of the clinical development of rituximab: first monoclonal antibody approved for the treatment of lymphoma. Semin Oncol. 1999 Oct;26(5 Suppl 14):66-73.
- Background: PubMed 10482196Shak S. Overview of the trastuzumab (Herceptin) anti-HER2 monoclonal antibody clinical program in HER2-overexpressing metastatic breast cancer. Herceptin Multinational Investigator Study Group. Semin Oncol. 1999 Aug;26(4 Suppl 12):71-7.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HeFi-1 Monoclonal Antibody in people with Neoplasms, run by National Cancer Institute (NCI) at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00048880, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.