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

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

National Cancer Institute (NCI)

ClinicalTrials.gov Identifier:

NCT00017381

First received: June 6, 2001

Last updated: January 8, 2013

Last verified: January 2013

History of Changes

Tracking Information

First Received Date ^ICMJE

June 6, 2001

Last Updated Date

January 8, 2013

Start Date ^ICMJE

April 2001

Primary Completion Date

December 2007 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

MTD, defined in terms of clinical toxicities graded using the CTC version 2.0 [ Time Frame: Up to day 15 ] [ Designated as safety issue: Yes ]

The modified continual reassessment method (CRM) will be employed to estimate the MTD.

Original Primary Outcome Measures ^ICMJE

Not Provided

Change History

Complete list of historical versions of study NCT00017381 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

Not Provided

Original Secondary Outcome Measures ^ICMJE

Not Provided

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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

Brief Summary

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

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 ^ICMJE

Interventional

Study Phase

Phase 0

Study Design ^ICMJE

Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Condition ^ICMJE

Contiguous Stage II Adult Diffuse Large Cell Lymphoma
Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma
Contiguous Stage II Grade 1 Follicular Lymphoma
Contiguous Stage II Grade 2 Follicular Lymphoma
Contiguous Stage II Grade 3 Follicular Lymphoma
Contiguous Stage II Mantle Cell Lymphoma
Contiguous Stage II Marginal Zone Lymphoma
Contiguous Stage II Small Lymphocytic Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma
Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma
Noncontiguous Stage II Grade 1 Follicular Lymphoma
Noncontiguous Stage II Grade 2 Follicular Lymphoma
Noncontiguous Stage II Grade 3 Follicular Lymphoma
Noncontiguous Stage II Mantle Cell Lymphoma
Noncontiguous Stage II Marginal Zone Lymphoma
Noncontiguous Stage II Small Lymphocytic Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Small Lymphocytic Lymphoma
Stage I Adult Diffuse Large Cell Lymphoma
Stage I Adult Diffuse Small Cleaved Cell Lymphoma
Stage I Grade 1 Follicular Lymphoma
Stage I Grade 2 Follicular Lymphoma
Stage I Grade 3 Follicular Lymphoma
Stage I Mantle Cell Lymphoma
Stage I Marginal Zone Lymphoma
Stage I Small Lymphocytic Lymphoma
Stage III Adult Diffuse Large Cell Lymphoma
Stage III Adult Diffuse Small Cleaved Cell Lymphoma
Stage III Grade 1 Follicular Lymphoma
Stage III Grade 2 Follicular Lymphoma
Stage III Grade 3 Follicular Lymphoma
Stage III Mantle Cell Lymphoma
Stage III Marginal Zone Lymphoma
Stage III Small Lymphocytic Lymphoma
Stage IV Adult Diffuse Large Cell Lymphoma
Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Marginal Zone Lymphoma
Stage IV Small Lymphocytic Lymphoma
Waldenström Macroglobulinemia

Intervention ^ICMJE

Biological: rituximab
Given IV
Other Names:
- IDEC-C2B8
- IDEC-C2B8 monoclonal antibody
- Mabthera
- MOAB IDEC-C2B8
- Rituxan
Drug: cyclophosphamide
Given IV
Other Names:
- CPM
- CTX
- Cytoxan
- Endoxan
- Endoxana
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

Study Arm (s)

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 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.

Interventions:

Biological: rituximab
Drug: cyclophosphamide
Biological: filgrastim
Radiation: yttrium Y 90 ibritumomab tiuxetan
Procedure: peripheral blood stem cell transplantation

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Completed

Estimated Enrollment ^ICMJE

Completion Date

Not Provided

Primary Completion Date

December 2007 (final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Gender

Both

Ages

18 Years to 70 Years

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Location Countries ^ICMJE

United States

Administrative Information

NCT Number ^ICMJE

NCT00017381

Other Study ID Numbers ^ICMJE

NCI-2012-03156, J0004

Has Data Monitoring Committee

Not Provided

Responsible Party

National Cancer Institute (NCI)

Study Sponsor ^ICMJE

National Cancer Institute (NCI)

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Principal Investigator:

Lode Swinnen

Johns Hopkins University

Information Provided By

National Cancer Institute (NCI)

Verification Date

January 2013

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

To Top