NCT00017381

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

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P50-P75 for early_phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2001

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

June 6, 2001

Completed
1.6 years until next milestone

First Posted

Study publicly available on registry

January 27, 2003

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2007

Completed
Last Updated

January 9, 2013

Status Verified

January 1, 2013

Enrollment Period

6.7 years

First QC Date

June 6, 2001

Last Update Submit

January 8, 2013

Conditions

Contiguous Stage II Adult Diffuse Large Cell LymphomaContiguous Stage II Adult Diffuse Small Cleaved Cell LymphomaContiguous Stage II Grade 1 Follicular LymphomaContiguous Stage II Grade 2 Follicular LymphomaContiguous Stage II Grade 3 Follicular LymphomaContiguous Stage II Mantle Cell LymphomaContiguous Stage II Marginal Zone LymphomaContiguous Stage II Small Lymphocytic LymphomaExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueNoncontiguous Stage II Adult Diffuse Large Cell LymphomaNoncontiguous Stage II Adult Diffuse Small Cleaved Cell LymphomaNoncontiguous Stage II Grade 1 Follicular LymphomaNoncontiguous Stage II Grade 2 Follicular LymphomaNoncontiguous Stage II Grade 3 Follicular LymphomaNoncontiguous Stage II Mantle Cell LymphomaNoncontiguous Stage II Marginal Zone LymphomaNoncontiguous Stage II Small Lymphocytic LymphomaRecurrent Adult Diffuse Large Cell LymphomaRecurrent Adult Diffuse Small Cleaved Cell LymphomaRecurrent Grade 1 Follicular LymphomaRecurrent Grade 2 Follicular LymphomaRecurrent Grade 3 Follicular LymphomaRecurrent Mantle Cell LymphomaRecurrent Marginal Zone LymphomaRecurrent Small Lymphocytic LymphomaStage I Adult Diffuse Large Cell LymphomaStage I Adult Diffuse Small Cleaved Cell LymphomaStage I Grade 1 Follicular LymphomaStage I Grade 2 Follicular LymphomaStage I Grade 3 Follicular LymphomaStage I Mantle Cell LymphomaStage I Marginal Zone LymphomaStage I Small Lymphocytic LymphomaStage III Adult Diffuse Large Cell LymphomaStage III Adult Diffuse Small Cleaved Cell LymphomaStage III Grade 1 Follicular LymphomaStage III Grade 2 Follicular LymphomaStage III Grade 3 Follicular LymphomaStage III Mantle Cell LymphomaStage III Marginal Zone LymphomaStage III Small Lymphocytic LymphomaStage IV Adult Diffuse Large Cell LymphomaStage IV Adult Diffuse Small Cleaved Cell LymphomaStage IV Grade 1 Follicular LymphomaStage IV Grade 2 Follicular LymphomaStage IV Grade 3 Follicular LymphomaStage IV Mantle Cell LymphomaStage IV Marginal Zone LymphomaStage IV Small Lymphocytic LymphomaWaldenström Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

  • MTD, defined in terms of clinical toxicities graded using the CTC version 2.0

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

    Up to day 15

Study Arms (1)

Treatment

EXPERIMENTAL

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.

Biological: rituximabDrug: cyclophosphamideBiological: filgrastimRadiation: yttrium Y 90 ibritumomab tiuxetanProcedure: peripheral blood stem cell transplantation

Interventions

rituximabBIOLOGICAL

Given IV

Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan
Treatment
cyclophosphamideDRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana
Treatment
filgrastimBIOLOGICAL

Given SC

Also known as: G-CSF, Neupogen
Treatment
yttrium Y 90 ibritumomab tiuxetanRADIATION

Given IV

Also known as: 90Y ibritumomab tiuxetan, IDEC Y2B8, Y90 Zevalin, Y90-labeled ibritumomab tiuxetan
Treatment
peripheral blood stem cell transplantationPROCEDURE

Undergo PBSCT

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Treatment

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21287-8936, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinLymphoma, FollicularLymphoma, Mantle-CellLymphoma, B-Cell, Marginal ZoneLeukemia, Lymphocytic, Chronic, B-CellWaldenstrom Macroglobulinemia

Interventions

RituximabCyclophosphamideFilgrastimGranulocyte Colony-Stimulating Factoribritumomab tiuxetanPeripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Lymphoma, B-CellLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLeukemia, B-CellLeukemia, LymphoidLeukemiaHematologic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsColony-Stimulating FactorsGlycoproteinsGlycoconjugatesCarbohydratesHematopoietic Cell Growth FactorsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesBiological FactorsHematopoietic Stem Cell TransplantationStem Cell TransplantationCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsTransplantationSurgical Procedures, Operative

Study Officials

  • Lode Swinnen

    Johns Hopkins University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 6, 2001

First Posted

January 27, 2003

Study Start

April 1, 2001

Primary Completion

December 1, 2007

Last Updated

January 9, 2013

Record last verified: 2013-01

Locations

US(1)