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

July 9, 2018 updated by: National Cancer Institute (NCI)

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. 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.

Study Type

Interventional

Enrollment (Actual)

81

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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
    • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Treatment (radiolabeled monoclonal antibody therapy)
Patients 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.
Biological: rituximab
Given IV
Other Names:
  • Rituxan
  • Mabthera
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • MOAB IDEC-C2B8
Biological: filgrastim
Given subcutaneously
Other Names:
  • G-CSF
  • Neupogen
Biological: yttrium Y 90 ibritumomab tiuxetan
Given IV
Other Names:
  • 90Y ibritumomab tiuxetan
  • IDEC Y2B8
  • Y90 Zevalin
  • Y90-labeled ibritumomab tiuxetan
Biological: indium In 111 ibritumomab tiuxetan
Given IV
Other Names:
  • IDEC-In2B8
Biological: oprelvekin
Given subcutaneously
Other Names:
  • IL-11
  • Neumega
  • adipogenesis inhibitory factor
  • interleukin 11

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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

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.
At 8 weeks
Toxicity of Single-dose Y2B8 Radioimmunotherapy With and Without the Use of Growth Factors (Phase I)
Time Frame: Assessed up to week 24
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.
Assessed up to week 24
Proportion of Patients Who Receive 2 Sequential Doses of Y2B8 Immunotherapy and Are Progression-free (Phase II)
Time Frame: At 3 years
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.
At 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Association Between the Amounts of Tumor Radiation Indicated by the In2B8 Scan and Tumor Response (Phase I)
Time Frame: At week 12
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.
At week 12
Association Between In2B8 Scan and Positron Emission Tomography Scan Results (Phase I)
Time Frame: At week 12
Explored using a contingency table and sensitivity and specificity will be calculated using 90% exact confidence intervals.
At week 12
Appearance of Tumor and Normal Organ Images on the Second In2B8 Scan (Phase I)
Time Frame: At week 12
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.
At week 12
Survival (Phase II)
Time Frame: From registration to death due to any cause, assessed up to 5 years
Estimated using the method of Kaplan-Meier.
From registration to death due to any cause, assessed up to 5 years
Time to Disease Progression (Phase II)
Time Frame: From registration to the earliest date documentation of>disease progression, assessed up to 5 years
Estimated using the method of Kaplan-Meier.
From registration to the earliest date documentation of>disease progression, assessed up to 5 years
Tumor Response Rate (Phase II)
Time Frame: Assessed up to 5 years
Calculated by the number of tumor responses divided by the total number of evaluable patients. An exact binomial confidence interval will be calculated.
Assessed up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2001

Primary Completion (ACTUAL)

April 1, 2010

Study Completion (ACTUAL)

April 1, 2010

Study Registration Dates

First Submitted

March 3, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (ESTIMATE)

January 27, 2003

Study Record Updates

Last Update Posted (ACTUAL)

August 9, 2018

Last Update Submitted That Met QC Criteria

July 9, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2009-00008 (REGISTRY: CTRP (Clinical Trial Reporting Program))
  • 312 (CTEP)
  • CDR0000068503
  • MC998C (OTHER: Mayo Clinic)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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