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Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissuePhase 1/2NCT00012298

Radiolabeled Monoclonal Antibody Plus Rituximab With and Without Filgrastim and Interleukin-11 in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

A Phase 1/2 study testing rituximab, yttrium Y 90 ibritumomab tiuxetan and indium In 111 ibritumomab tiuxetan in people with Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue and Nodal Marginal Zone B-cell Lymphoma, run by National Cancer Institute (NCI) at 1 site 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

Phase I/II trial to study the effectiveness of combining radiolabeled monoclonal antibody therapy and rituximab with and without filgrastim and interleukin-11 in treating patients who have relapsed or refractory non-Hodgkin's lymphoma. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
rituximab, yttrium Y 90 ibritumomab tiuxetan and indium In 111 ibritumomab tiuxetan
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
81 participants
Where
1 siteUnited States
Study dates
Apr 2001to Apr 2010
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Histologically proven relapsed or refractory low-grade or follicular CD+ non-Hodgkin lymphoma, including 1 of the following:
  • Small lymphocytic lymphoma
  • Lymphoplasmacytoid lymphoma
  • Follicular center lymphoma (grades I, II, and III)
  • Extranodal marginal zone B-cell lymphoma
  • Nodal marginal zone B-cell lymphoma
Show all 33Show fewer
  • Splenic marginal zone B-cell lymphoma (monocytoid B-cell lymphoma)
  • Less than 25% bone marrow involvement of cellular marrow with lymphoma by bilateral bone marrow aspirate and biopsy
  • ECOG performance status 0-2
  • Bidimensionally measurable disease with at least 1 lesion >= 2 cm in the greatest diameter
  • No prior myeloablative therapy with autologous or allogeneic bone marrow transplantation or peripheral blood stem cell support
  • No concurrent corticosteroid therapy, except prednisone (or equivalent) for adrenal failure or < 20mg of prednisone daily
  • No prior external beam radiotherapy to >25% of active bone marrow
  • More than 4 weeks since prior surgery other than diagnostic surgery
  • No other concurrent myelosuppressive antineoplastic agents
  • No prior radioimmunotherapy, including yttrium Y 90 ibritumomab tiuxetan or iodine I 131 monoclonal antibody tositumomab or Lym-1
  • No CNS lymphoma
  • No myelodysplastic syndromes or marrow chromosomal changes suggesting myelodysplasia
  • No HIV or AIDS-related lymphoma
  • No pleural effusion or ascites with lymphoma cells
  • No active infection
  • No other serious non-malignant disease that would preclude study participation
  • No other active primary malignancy
  • No known human anti-mouse or human anti-chimeric antibody
  • No prior skin rash (e.g., Stevens-Johnsons syndrome or toxic epidermal necrolysis) from rituximab therapy
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelet count >= 150,000/mm^3
  • Total lymphocyte count < 5,000/mm^3 for patients with small lymphocytic lymphoma
  • Bilirubin =< 2 mg/dL
  • Creatinine =< 2 mg/dL

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: Phase I/II Study of Two Sequential Doses of IDEC-Y2B8 in Patients With Relapsed Low-Grade and Follicular Non-Hodgkin's Lymphoma

Phase I/II trial to study the effectiveness of combining radiolabeled monoclonal antibody therapy and rituximab with and without filgrastim and interleukin-11 in treating patients who have relapsed or refractory non-Hodgkin's lymphoma. Radiolabeled monoclonal antibodies can locate cancer cells and deliver cancer-killing substances to them without harming normal cells. Biological therapies such as filgrastim and interleukin-11 use different ways to stimulate the immune system and stop cancer cells from growing.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the maximum tolerated dose (MTD) of yttrium Y 90 ibritumomab tiuxetan (IDEC-90Y2B8) administered with rituximab with and without filgrastim (G-CSF) and interleukin-11 (IL-11) in patients with relapsed low-grade or follicular CD20+ non-Hodgkin's lymphoma. (Phase I) II. Determine the toxicity of this regimen in these patients. III. Determine the response rate in patients treated with this regimen. IV. Compare tumor and normal organ dosimetry with positron emission tomography and computerized tomography scans, subsequent tumor response, and normal organ toxicity by utilizing indium In 111 ibritumomab tiuxetan radioimmunoconjugate scans before each IDEC-90Y2B8 dose in these patients. (Phase I) V. Determine the immune response to this regimen, in terms of human anti-mouse and human anti-chimeric antibody formation, in these patients. (Phase I) VI. Determine whether G-CSF and IL-11 can ameliorate the effect of the MTD of IDEC-90Y2B8 on bone marrow function in these patients. (Phase I) VII. Determine progression-free survival at 3 years. (Phase II)

OUTLINE:

PHASE I: Patients receive rituximab IV on days 1 and 8, indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1 (for radioimaging), and IDEC-90Y2B8 IV over 10 minutes on day 8. Treatment repeats 24-36 weeks later for a total of 2 courses in the absence of disease progression or unacceptable toxicity. Once the maximum tolerated dose (MTD) of IDEC-90Y2B8 is determined, patients also receive filgrastim (G-CSF) subcutaneously (SC) daily beginning when absolute neutrophil count is less than 1,500/mm3 and continuing until blood counts recover. Patients also receive interleukin-11 (IL-11) SC beginning when platelet count is less than 75,000/mm^3 and continuing until blood counts recover. Patients undergo PBSC transplantation only if marrow recovery is inadequate.

Cohorts of 3-6 patients receive escalating doses of IDEC-90Y2B8 until the MTD is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to determine the MTD of this radioimmunotherapy with the addition of the prophylactic cytokines, G-CSF and IL-11.

PHASE II: Patients receive rituximab, indium In 111 ibritumomab tiuxetan, and IDEC-90Y2B8 IV as determined at the MTD in phase I. Treatment repeats 24-36 weeks later for a total of 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually for 2 years.

Being tested
rituximab, yttrium Y 90 ibritumomab tiuxetan, indium In 111 ibritumomab tiuxetan, oprelvekin, filgrastim
Medical subject headings
Lymphoma, B-Cell, Marginal Zone, Lymphoma, Follicular, Leukemia, Lymphocytic, Chronic, B-Cell, Waldenstrom Macroglobulinemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • rituximabBiological

    Also called IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8

    Given IV

  • yttrium Y 90 ibritumomab tiuxetanBiological

    Also called 90Y ibritumomab tiuxetan, IDEC Y2B8, Y90 Zevalin, Y90-labeled ibritumomab tiuxetan

    Given IV

  • indium In 111 ibritumomab tiuxetanBiological

    Also called IDEC-In2B8

    Given IV

  • oprelvekinBiological

    Also called adipogenesis inhibitory factor, IL-11, interleukin 11, Neumega

    Given subcutaneously

  • filgrastimBiological

    Also called G-CSF, Neupogen

    Given subcutaneously

Study groups in NCT00012298
Study groupRoleWhat they receive
Treatment (radiolabeled monoclonal antibody therapy)ExperimentalPatients receive rituximab IV on days 1 and 8, indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1, and yttrium Y 90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive filgrastim (G-CSF) subcutaneously (SC) and interleukin-11 SC until blood counts recover.
Receives: Biological: rituximab; Biological: yttrium Y 90 ibritumomab tiuxetan; Biological: indium In 111 ibritumomab tiuxetan; Biological: oprelvekin; Biological: filgrastim

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD) of Yttrium Y-90 Ibritumomab Tiuxetan (Y2B8) With and Without Filgrastim (G-CSF) and Interleukin-11 (IL-11) (Phase I)

    This study is a series of 3 single-arm phase-I trials designed to determine the maximum tolerated dose (MTD) of a 2-cycle combination regimen containing Rituxan + Y2B8 radioimmunotherapy with and without the use of G-CSF and IL-11. Trial 1 will determine the Y2B8 MTD in the combined regimen without growth factors. Trial 2 will evaluate the combined regimen with growth factors. Trial 3 starts IL-11 earlier (when platelet count drops below 150000) and reduces the dosing interval to twice weekly.

    > Dose-limiting toxicity (DLT) is defined as an adverse event in the second cycle attributed to treatment and meeting the following criteria: Grade 4 ANC or platelet decrease for 14 days, or grade 3 for 28 days, or any other grade 3 Non-Heme event.

    > If at any time 2 or more patients (of a maximum of 6) at any dose level experience DLT, then the MTD will be defined as the previous dose level during that trial. The number of patients with a DLT are reported here.

    Measured: At 8 weeks

  2. Toxicity of Single-dose Y2B8 Radioimmunotherapy With and Without the Use of Growth Factors (Phase I)

    Evaluated using the Common Toxicity Criteria (CTC) version 2.0. This data is presented as the number of patients reporting grade 3 or higher, grade 4 or higher, or grade 5 adverse events regardless of event attribution.

    Measured: Assessed up to week 24

  3. Proportion of Patients Who Receive 2 Sequential Doses of Y2B8 Immunotherapy and Are Progression-free (Phase II)

    Estimated by the number of successes divided by the total number of evaluable patients. Exact binomial confidence intervals for the true success proportion will be calculated.

    Measured: At 3 years

Secondary outcomes (6)

  1. Association Between the Amounts of Tumor Radiation Indicated by the In2B8 Scan and Tumor Response (Phase I)

    Assessed using a correlated logistic regression model and generalized estimating equations (GEE). Covariates such as dose level and use of prophylactic cytokines may also be included in this model. A Wilcoxon test will be used to assess the equality of the distributions of the continuous levels of predicted tumor radiation from the In2B8 scans by response.

    Measured: At week 12

  2. Association Between In2B8 Scan and Positron Emission Tomography Scan Results (Phase I)

    Explored using a contingency table and sensitivity and specificity will be calculated using 90% exact confidence intervals.

    Measured: At week 12

  3. Appearance of Tumor and Normal Organ Images on the Second In2B8 Scan (Phase I)

    Calculated from the serial gamma camera images. Compared using a signed-rank-test. Scatter plots will be used to further explore relationships between these residence times and Bland- Altman methods can be used to assess the agreement between the first and second In2B8 scan residence times.

    Measured: At week 12

  4. Survival (Phase II)

    Estimated using the method of Kaplan-Meier.

    Measured: From registration to death due to any cause, assessed up to 5 years

  5. Time to Disease Progression (Phase II)

    Estimated using the method of Kaplan-Meier.

    Measured: From registration to the earliest date documentation of>disease progression, assessed up to 5 years

  6. Tumor Response Rate (Phase II)

    Calculated by the number of tumor responses divided by the total number of evaluable patients. An exact binomial confidence interval will be calculated.

    Measured: Assessed up to 5 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 startApr 2001
  3. Primary completionApr 2010
  4. Study completionApr 2010

Why it stopped: Trial completed prematurely.

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
81 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00012298
Sponsor's protocol ID
NCI-2009-00008
Other IDs
NCI-2009-00008, CDR0000068503, MC998C, 312
Status last verified
Jul 2018
First submitted
3 Mar 2001
Last updated
9 Aug 2018

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing rituximab, yttrium Y 90 ibritumomab tiuxetan and indium In 111 ibritumomab tiuxetan in people with Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue and Nodal Marginal Zone B-cell Lymphoma, run by National Cancer Institute (NCI) at 1 site 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 33 inclusion and 0 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: stopped early, as of the sponsor's last update on 9 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Maximum Tolerated Dose (MTD) of Yttrium Y-90 Ibritumomab Tiuxetan (Y2B8) With and Without Filgrastim (G-CSF) and Interleukin-11 (IL-11) (Phase I) (time frame: At 8 weeks). The study lists 3 primary outcomes in all. 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 NCT00012298.

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 9 Aug 2018.

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