LymphomaPhase 1NCT00033423
Radiolabeled Monoclonal Antibody in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
A Phase 1 study testing rituximab and yttrium Y 90 ibritumomab tiuxetan in people with Lymphoma, run by University of Alabama at Birmingham at 3 sites in United States.
Trial summary
RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody in treating patients who have relapsed or refractory non-Hodgkin's lymphoma. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Lymphoma
- What is being tested?
- rituximab and yttrium Y 90 ibritumomab tiuxetan
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 3 sitesUnited States
- Study dates
- Aug 2001to May 2009
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed low-grade, follicular, or transformed CD20-positive B-cell non-Hodgkin's lymphoma (NHL)
- Relapsed after prior chemotherapy OR chemotherapy-resistant disease
- Failed at least 1 prior chemotherapy regimen
- CD20-positive B-cell population in lymph nodes or bone marrow for International Working Formulation A (small lymphocytic lymphoma) and transformed NHL
- Bone marrow involvement with lymphoma less than 25% bilaterally
- No impaired bone marrow reserve defined as at least 1 of the following criteria:
- Prior myeloablative therapies with bone marrow transplantation or peripheral blood stem cell rescue
- Platelet count less than 100,000/mm3
- Bone marrow cellularity no greater than 15%
- Marked reduction in bone marrow precursors of one or more cell lines (e.g., granulocytic, megakaryocytic, or erythroid)
- Failed prior stem cell collection
- No CNS lymphoma, chronic lymphocytic lymphoma, or HIV or AIDS-related lymphoma
- No diffuse small lymphocytic/marginal zone lymphoma with lymphocyte count greater than 5,000/mm^3
- No pleural effusion NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.
PATIENT CHARACTERISTICS:
Age:
- 19 and over
Performance status:
- WHO 0-2
Life expectancy:
- At least 6 months
Hematopoietic:
- See Disease Characteristics
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Hematocrit greater than 30%
- Hemoglobin greater than 9.0 g/dL
Hepatic:
- Bilirubin no greater than 1.5 mg/dL
Renal:
- Creatinine no greater than 1.5 mg/dL
Other:
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 6 months after study participation
- No anti-murine antibody reactivity if prior exposure to murine antibodies or proteins
- No other primary malignancy
- No other serious nonmalignant disease or infection that would preclude study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- See Disease Characteristics
- No prior radioimmunotherapy
- Prior rituximab allowed if more than 6 months to progression after an objective response
- At least 6 weeks since prior rituximab
- At least 3 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
- Recovered from prior immunotherapy
Chemotherapy:
- See Disease Characteristics
- No prior fludarabine
- At least 3 weeks since prior anticancer chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- No concurrent chemotherapy
Endocrine therapy:
- At least 3 weeks since prior anticancer endocrine therapy
- No concurrent high-dose systemic corticosteroids (e.g., 50 mg or more of prednisone as a single dose or 50 mg or less of prednisone for more than 6 doses)
Radiotherapy:
- No prior radiotherapy to more than 25% of active bone marrow (involved field or regional)
- At least 3 weeks since prior anticancer radiotherapy and recovered
Surgery:
- At least 4 weeks since prior surgery (except diagnostic surgery) and recovered
Other:
- No other concurrent anticancer therapy
- Concurrent oral anticoagulant therapy allowed if platelet count is at least 30,000/mm3
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Lurleen Wallace Comprehensive Cancer at University of Alabama-Birmingham
Birmingham, Alabama, 35294
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905
Stanford Comprehensive Cancer Center - Stanford
Stanford, California, 94305
About this study
Official title: Phase I, Multicenter, Open Label, Dose Escalation Of 90Y-Zevalin Radioimmunotherapy Using A Modified Treatment Regimen For Relapsed Or Refractory CD20+ B-Cell (Follicular/Transformed) Non-Hodgkin's Lymphoma
RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.
PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody in treating patients who have relapsed or refractory non-Hodgkin's lymphoma.
Read the detailed description
OBJECTIVES:
- Determine the maximum tolerated dose of yttrium Y 90 ibritumomab tiuxetan when administered in combination with rituximab in patients with relapsed or refractory low-grade, follicular, or transformed CD20-positive B-cell non-Hodgkin's lymphoma (NHL).
- Determine the toxicity of different doses of yttrium Y 90 ibritumomab tiuxetan in patients treated with this regimen.
- Determine the frequency of reversal of bone marrow involvement with NHL in patients treated with this regimen.
- Determine the antitumor response in patients treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of yttrium Y 90 ibritumomab tiuxetan.
Patients receive rituximab IV once weekly on weeks 1-4. After 4 doses of rituximab, patients without bone marrow involvement and cellularity greater than 50% expected receive rituximab IV once weekly on weeks 6 and 7 and yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes with the final dose of rituximab (day 43).
Cohorts of 5-6 patients receive escalating dose of yttrium Y 90 ibritumomab tiuxetan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 4 of 5 or 3 of 6 patients experience dose-limiting toxicity.
Patients are followed at 6 and 12 weeks, every 2-3 months for 2 years, and then every 6 months for 2 years.
PROJECTED ACCRUAL: Approximately 6-30 patients will be accrued for this study.
- Conditions
- Lymphoma
- Being tested
- rituximab, yttrium Y 90 ibritumomab tiuxetan
- Keywords
- recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma
- Medical subject headings
- Lymphoma, Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rituximabBiological
yttrium Y 90 ibritumomab tiuxetanRadiation
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | First radiation dose regimen of yttrium Y 90 ibritumomab tiuxetan Receives: Biological: rituximab; Radiation: yttrium Y 90 ibritumomab tiuxetan |
| Cohort II | Experimental | Second radiation dose regimen of yttrium Y 90 ibritumomab tiuxetan Receives: Biological: rituximab; Radiation: yttrium Y 90 ibritumomab tiuxetan |
| Cohort III | Experimental | Third radiation dose regimen of yttrium Y 90 ibritumomab tiuxetan Receives: Biological: rituximab; Radiation: yttrium Y 90 ibritumomab tiuxetan |
| Cohort IV | Experimental | Fourth radiation dose regimen of yttrium Y 90 ibritumomab tiuxetan Receives: Biological: rituximab; Radiation: yttrium Y 90 ibritumomab tiuxetan |
| Cohort V | Experimental | MTD radiation dose regimen of yttrium Y 90 ibritumomab tiuxetan Receives: Biological: rituximab; Radiation: yttrium Y 90 ibritumomab tiuxetan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the maximum tolerated dose of yttrium Y 90 ibritumomab tiuxetan when administered in combination with rituximab in patients with relapsed or refractory low-grade, follicular, or transformed CD20-positive B-cell non-Hodgkin's lymphoma (NHL).
Measured: baseline through 4 years
Secondary outcomes (3)
Determine the toxicity of different doses of yttrium Y 90 ibritumomab tiuxetan in patients treated with this regimen
Measured: baseline through 4 years
Determine the frequency of reversal of bone marrow involvement with NHL in patients treated with this regimen.
Measured: baseline through 4 years
Determine the antitumor response in patients treated with this regimen.
Measured: baseline through 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startAug 2001
- Primary completionMay 2009
- Study completionMay 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe 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
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Andres Forero-Torres, MD, CSU, Study chair, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00033423
- Sponsor's protocol ID
- CDR0000069282
- Other IDs
- UAB-0127, UAB-F010806018, NCI-G02-2053
- Status last verified
- Dec 2013
- First submitted
- 9 Apr 2002
- Last updated
- 13 Dec 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Forero-Torres A, Besh S, Knox S, et al.: Higher doses of Rituxan alter pharmacokinetics and biodistribution of Zevalin but may increase responses; a preliminary report of a phase I study of Zevalin using a modified treatment regimen for relapsed or refractory CD20+ B-Cell follicular/transformed non-Hodgkins lymphoma. [Abstract] Blood 102 (11 Pt 1): A-1483, 2003.
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I, Multicenter, Open Label, Dose Escalation Of 90Y-Zevalin Radioimmunotherapy Using A Modified Treatment Regimen For Relapsed Or Refractory CD20+ B-Cell (Follicular/Transformed) Non-Hodgkin's Lymphoma
- ClinicalTrials.gov ID
- NCT00033423
- Acronym / sponsor ID
- CDR0000069282
- Conditions
- Lymphoma
- Keywords
- recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Aug 2001
- Primary completion
- May 2009 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 27 Jan 2003 (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.
RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.
PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody in treating patients who have relapsed or refractory non-Hodgkin's lymphoma.
Detailed description
OBJECTIVES:
- Determine the maximum tolerated dose of yttrium Y 90 ibritumomab tiuxetan when administered in combination with rituximab in patients with relapsed or refractory low-grade, follicular, or transformed CD20-positive B-cell non-Hodgkin's lymphoma (NHL).
- Determine the toxicity of different doses of yttrium Y 90 ibritumomab tiuxetan in patients treated with this regimen.
- Determine the frequency of reversal of bone marrow involvement with NHL in patients treated with this regimen.
- Determine the antitumor response in patients treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of yttrium Y 90 ibritumomab tiuxetan.
Patients receive rituximab IV once weekly on weeks 1-4. After 4 doses of rituximab, patients without bone marrow involvement and cellularity greater than 50% expected receive rituximab IV once weekly on weeks 6 and 7 and yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes with the final dose of rituximab (day 43).
Cohorts of 5-6 patients receive escalating dose of yttrium Y 90 ibritumomab tiuxetan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 4 of 5 or 3 of 6 patients experience dose-limiting toxicity.
Patients are followed at 6 and 12 weeks, every 2-3 months for 2 years, and then every 6 months for 2 years.
PROJECTED ACCRUAL: Approximately 6-30 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Biological: rituximab, Radiation: yttrium Y 90 ibritumomab tiuxetanFirst radiation dose regimen of yttrium Y 90 ibritumomab tiuxetan |
| Cohort II | Experimental | Biological: rituximab, Radiation: yttrium Y 90 ibritumomab tiuxetanSecond radiation dose regimen of yttrium Y 90 ibritumomab tiuxetan |
| Cohort III | Experimental | Biological: rituximab, Radiation: yttrium Y 90 ibritumomab tiuxetanThird radiation dose regimen of yttrium Y 90 ibritumomab tiuxetan |
| Cohort IV | Experimental | Biological: rituximab, Radiation: yttrium Y 90 ibritumomab tiuxetanFourth radiation dose regimen of yttrium Y 90 ibritumomab tiuxetan |
| Cohort V | Experimental | Biological: rituximab, Radiation: yttrium Y 90 ibritumomab tiuxetanMTD radiation dose regimen of yttrium Y 90 ibritumomab tiuxetan |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| rituximab | Biological | Cohort 1, Cohort II, Cohort III, Cohort IV, Cohort V |
| yttrium Y 90 ibritumomab tiuxetan | Radiation | Cohort 1, Cohort II, Cohort III, Cohort IV, Cohort V |
Primary outcome
Determine the maximum tolerated dose of yttrium Y 90 ibritumomab tiuxetan when administered in combination with rituximab in patients with relapsed or refractory low-grade, follicular, or transformed CD20-positive B-cell non-Hodgkin's lymphoma (NHL).
Time frame: baseline through 4 years
3 secondary outcomes
Determine the toxicity of different doses of yttrium Y 90 ibritumomab tiuxetan in patients treated with this regimen
Time frame: baseline through 4 years
Determine the frequency of reversal of bone marrow involvement with NHL in patients treated with this regimen.
Time frame: baseline through 4 years
Determine the antitumor response in patients treated with this regimen.
Time frame: baseline through 4 years
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2013.
- Results publicationForero-Torres A, Besh S, Knox S, et al.: Higher doses of Rituxan alter pharmacokinetics and biodistribution of Zevalin but may increase responses; a preliminary report of a phase I study of Zevalin using a modified treatment regimen for relapsed or refractory CD20+ B-Cell follicular/transformed non-Hodgkins lymphoma. [Abstract] Blood 102 (11 Pt 1): A-1483, 2003.
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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.
Andres Forero-Torres, MD, CSU study chair
University of Alabama at Birmingham
3 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 rituximab and yttrium Y 90 ibritumomab tiuxetan in people with Lymphoma, run by University of Alabama at Birmingham at 3 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?
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: stopped early, as of the sponsor's last update on 13 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 was stopped early. Results are not available in the source record.
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.
What does the primary outcome measure?
Determine the maximum tolerated dose of yttrium Y 90 ibritumomab tiuxetan when administered in combination with rituximab in patients with relapsed or refractory low-grade, follicular, or transformed CD20-positive B-cell non-Hodgkin's lymphoma (NHL). (time frame: baseline through 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00033423, which also lists 1 linked publication.
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 13 Dec 2013.