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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.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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

Other trials in United States

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 groups in NCT00033423
Study groupRoleWhat they receive
Cohort 1ExperimentalFirst radiation dose regimen of yttrium Y 90 ibritumomab tiuxetan
Receives: Biological: rituximab; Radiation: yttrium Y 90 ibritumomab tiuxetan
Cohort IIExperimentalSecond radiation dose regimen of yttrium Y 90 ibritumomab tiuxetan
Receives: Biological: rituximab; Radiation: yttrium Y 90 ibritumomab tiuxetan
Cohort IIIExperimentalThird radiation dose regimen of yttrium Y 90 ibritumomab tiuxetan
Receives: Biological: rituximab; Radiation: yttrium Y 90 ibritumomab tiuxetan
Cohort IVExperimentalFourth radiation dose regimen of yttrium Y 90 ibritumomab tiuxetan
Receives: Biological: rituximab; Radiation: yttrium Y 90 ibritumomab tiuxetan
Cohort VExperimentalMTD 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.

  1. 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)
  1. Determine the toxicity of different doses of yttrium Y 90 ibritumomab tiuxetan in patients treated with this regimen

    Measured: baseline through 4 years

  2. Determine the frequency of reversal of bone marrow involvement with NHL in patients treated with this regimen.

    Measured: baseline through 4 years

  3. 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.

  1. First posted27 Jan 2003 (estimated)
  2. Study startAug 2001
  3. Primary completionMay 2009
  4. Study completionMay 2009

Resources

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)
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.

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.

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