Monoclonal Antibody Therapy and Peripheral Stem Cell Transplant in Treating Patients With Non-Hodgkin's Lymphoma

January 8, 2013 updated by: National Cancer Institute (NCI)

Dose Finding Study of IDEC-Y2B8 With Autologous Stem Cell Support

This phase I trial is studying how well monoclonal antibody therapy with peripheral stem cell transplant works in treating patients with non-Hodgkin's lymphoma. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Peripheral stem cell transplant may allow the doctor to give higher doses of monoclonal antibodies and kill more cancer cells

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose of IDEC-Y2B8 when administered with rituximab in vivo purging and autologous stem cell rescue.

II. To obtain correlative laboratory data of in vivo purging with rituximab in patients with 0-35% marrow involvement.

OUTLINE: This is a multicenter, dose-escalation study of yttrium Y 90 ibritumomab tiuxetan (IDEC-Y2B8).

PART I: Patients receive rituximab IV on days 1, 8, 15, and 22 and cyclophosphamide IV over 1 hour on day 25. Filgrastim (G-CSF) is administered subcutaneously (SC) daily beginning on day 26 and continuing until autologous peripheral blood stem cells (PBSC) are harvested.

PART II: Beginning 4-6 weeks after completion of the fourth rituximab infusion, patients receive indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1 followed by dosimetry imaging on days 1, 2, 4, and 7. Patients then receive IDEC-Y2B8 IV over 10 minutes once between days 8-15.

The initial 3 patients receive the same dose of IDEC-Y2B8 and then subsequent cohorts of 3-5 patients receive escalating doses of IDEC-Y2B8 until the maximum tolerated dose is determined.

PART III: All patients undergo PBSC transplantation (PBSCT) beginning after residual bone marrow radioactivity resolves. G-CSF is administered SC beginning 1 day after PBSCT and continuing until blood counts recover.

Patients are followed every 3 months for 1 year and then every 6 months thereafter.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Early 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
    • Maryland
      • Baltimore, Maryland, United States, 21287-8936
        • Johns Hopkins University

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 to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • All patients must have a biopsy-proven indolent or diffuse large B-cell non-Hodgkin's lymphoma as defined as REAL classification marginal zone/MALT, mantle cell, plasmacytoid, lymphoplasmacytoid, small lymphocytic lymphoma or follicle center grades I, II, III or diffuse large B-cell (CLL patients will not be eligible); transformation from a low grade to intermediate or high grade lymphoma is also permissible; patients with diffuse large cell lymphoma must not be eligible for any known potentially curative therapy; at least one diagnostic pathologic specimen will be reviewed by the JHH Pathology Department
  • Patients must have received at least one but not more than five prior chemotherapy regimens for treatment of their lymphoma
  • Patients may not have received prior external beam radiation therapy to > 25% of active bone marrow (involved field or regional)
  • Patients must have 0-35% morphologically identifiable tumor in the trabecular space on bone marrow biopsy; in patients with lymphomas in whom tumor is morphologically difficult to distinguish from normal cells, flow cytometry must show 0-35% identifiable tumor within 4 weeks of registration
  • Patients must have =< 35% bone marrow involvement with tumor due to risk of engraftment failure
  • Patients may not have hypocellular bone marrow (=< 15% cellularity) or marked decrease in any one (or more) hematopoietic precursor
  • Patients may not have received prior murine compounds due to risk of HAMA formation
  • WBC must be >= 3,000
  • Total lymphocyte count must be < 5,000
  • Hgb must be >= 10.0
  • Platelets must be >= 75,000
  • Serum creatinine must not be greater than 2.0 mg/dl
  • Direct bilirubin must be =< 2mg/dl unless secondary to tumor
  • AST or ALT must be < 2 x the upper limit of normal
  • Normal (>= 45%) left ventricular cardiac ejection fraction, (determined by echocardiogram or MUGA scan)
  • DLCO must be > 50% predicted
  • Patients with active infections requiring oral or intravenous antibiotics are not eligible for entry onto the study until resolution of the infection
  • ECOG performance status =< 2
  • Not pregnant (confirmed by serum pregnancy test in females of reproductive potential) or breast feeding, because it is unknown what effect these drugs will have on children
  • Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception
  • Patients with a second malignancy other than basal cell carcinoma or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are not eligible unless the tumor was treated with curative intent at least two years previously
  • Women and minorities are encouraged to participate
  • Patients who have received prior anti-CD20 therapy must have achieved a partial or complete response
  • Patients who are HIV positive will be excluded due to increased risk for bone marrow suppression and other toxicities
  • Patients who have received prior radioimmunotherapy, for example Zevalin or Bexxar, are not eligible

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment

PART I: Patients receive rituximab IV on days 1, 8, 15, and 22 and cyclophosphamide IV over 1 hour on day 25. G-CSF is administered SC daily beginning on day 26 and continuing until autologous PBSC are harvested.

PART II: Beginning 4-6 weeks after completion of the fourth rituximab infusion, patients receive indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1 followed by dosimetry imaging on days 1, 2, 4, and 7. Patients then receive IDEC-Y2B8 IV over 10 minutes once between days 8-15.

PART III: All patients undergo PBSCT beginning after residual bone marrow radioactivity resolves. G-CSF is administered SC beginning 1 day after PBSCT and continuing until blood counts recover.
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • Endoxan
  • CPM
  • CTX
  • Endoxana
Biological: rituximab
Given IV
Other Names:
  • Rituxan
  • Mabthera
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • MOAB IDEC-C2B8
Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen
Radiation: yttrium Y 90 ibritumomab tiuxetan
Given IV
Other Names:
  • 90Y ibritumomab tiuxetan
  • IDEC Y2B8
  • Y90 Zevalin
  • Y90-labeled ibritumomab tiuxetan
Procedure: peripheral blood stem cell transplantation
Undergo PBSCT
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MTD, defined in terms of clinical toxicities graded using the CTC version 2.0
Time Frame: Up to day 15
The modified continual reassessment method (CRM) will be employed to estimate the MTD.
Up to day 15

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Lode Swinnen, Johns Hopkins University

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)

December 1, 2007

Study Registration Dates

First Submitted

June 6, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

January 9, 2013

Last Update Submitted That Met QC Criteria

January 8, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-03156
  • J0004

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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