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Chemotherapy With Monoclonal Antibody and Radioimmunotherapy for High-Risk B-Cell Non-Hodgkins Lymphoma

Primary Purpose

Lymphoma, B-Cell

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
cyclophosphamide
etoposide
rituximab
cytarabine
doxorubicin
tositumomab
Sponsored by
Duke University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma, B-Cell focused on measuring high risk non-hodgkins lymphoma, NHL, Bexxar, high dose chemotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Untreated, biopsy proven B-cell non-Hodgkin's lymphoma
  • Age >/= 18 years
  • No other prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for one year. The patient cannot have been exposed to chemotherapy to treat any of these diseases for at least 3 years prior to study entry.
  • Meet staging studies and laboratory tests prior to induction, consolidation and radioimmunotherapy.

Exclusion Criteria:

  • Significant medical and/or psychiatric illness which may compromise planned treatment;
  • Pregnant or lactating;
  • HIV-infection.
  • Patients with follicular lymphoma grade 1, 2 or 3A are not eligible for this trial.

Sites / Locations

  • Duke University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Induction + Consolidation + Bexxar

Arm Description

Induction:Cyclophosphamide, Etoposide, and Rituxan (rituximab) followed by Consolidation: Cytarabine and Doxorubicin followed by radioimmunotherapy: Bexxar (tositumomab)

Outcomes

Primary Outcome Measures

1 Year Progression-free Survival Rate
Progression-free survival is measured from the first day of induction chemotherapy to the date of progression, relapse or death. Definitions of response criteria are as described by Cheson. Progressive Disease: >50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal node for PDs or nonresponders, appearance of any new lesion during or at the end of therapy.

Secondary Outcome Measures

Disease-free Survival
Disease-free survival is measured from the date of CR or CRu to date of relapse or death
Overall Survival
Overall Survival is measured from the first day of chemotherapy until death from any cause.
Overall Response
Percent of subjects who achieved a complete response (CR) or partial response (PR) any time during the treatment period. CR = complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. PR = >/= 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. No increase should be observed in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter. Except splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. Patients who achieve a CR by the above criteria, but who have persistent morphologic bone marrow involvement will be considered partial responders. No new sites of disease should be observed.
Secondary Malignancies
The number of patients who develop secondary malignancies including solid tumors, acute leukemia and myelodysplasia or other bone marrow failure syndromes.

Full Information

First Posted
December 18, 2007
Last Updated
April 19, 2017
Sponsor
Duke University
Collaborators
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT00577629
Brief Title
Chemotherapy With Monoclonal Antibody and Radioimmunotherapy for High-Risk B-Cell Non-Hodgkins Lymphoma
Official Title
Dose-Intensive Chemotherapy Combined With Monoclonal Antibody Therapy and Targeted Radioimmunotherapy for Untreated Patients With High-Risk B-Cell Non-Hodgkin's Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
June 18, 2005 (Actual)
Primary Completion Date
April 8, 2012 (Actual)
Study Completion Date
November 3, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
GlaxoSmithKline

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to determine whether using high-dose chemotherapy, monoclonal antibodies, and targeted radioimmunotherapy will slow the progression of disease in patients with high-risk Non-Hodgkin's Lymphoma (NHL).
Detailed Description
This is a phase II efficacy trial for patients with untreated, high-risk, B-cell Non-Hodgkin's Lymphoma. The study will evaluate the efficacy and safety of high-dose chemotherapy combined with monoclonal antibodies and targeted radioimmunotherapy in previously untreated patients with high-risk NHL

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, B-Cell
Keywords
high risk non-hodgkins lymphoma, NHL, Bexxar, high dose chemotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
39 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Induction + Consolidation + Bexxar
Arm Type
Experimental
Arm Description
Induction:Cyclophosphamide, Etoposide, and Rituxan (rituximab) followed by Consolidation: Cytarabine and Doxorubicin followed by radioimmunotherapy: Bexxar (tositumomab)
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
Cytoxan®
Intervention Description
1.5g/m2 IV over 1 hour on days 1-4 of induction for a total dose of 6.0g/m2
Intervention Type
Drug
Intervention Name(s)
etoposide
Other Intervention Name(s)
VP-16
Intervention Description
300mg/m2 IV over 1 hour every 12 on days 1-3 of induction for a total dose of 1.8 g/m2.
Intervention Type
Drug
Intervention Name(s)
rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
375mg/m2 each week x 4 weeks of induction, beginning on day 1
Intervention Type
Drug
Intervention Name(s)
cytarabine
Other Intervention Name(s)
Ara-C
Intervention Description
3g/m2 IV over 1 hour every 12 during consolidation for a total of 8 doses
Intervention Type
Drug
Intervention Name(s)
doxorubicin
Other Intervention Name(s)
Adriamycin
Intervention Description
45mg/m2/day IV over 30 minutes on days 1, 2, 3 during consolidation
Intervention Type
Drug
Intervention Name(s)
tositumomab
Other Intervention Name(s)
Bexxar
Intervention Description
450mg unlabeled tositumomab over 1 hour, followed by 5 millicurie (mCi) Iodine I-131 labeled tositumomab over 20 minutes on day 0. Therapeutic dose of labeled tositumomab will be administered on day 15.
Primary Outcome Measure Information:
Title
1 Year Progression-free Survival Rate
Description
Progression-free survival is measured from the first day of induction chemotherapy to the date of progression, relapse or death. Definitions of response criteria are as described by Cheson. Progressive Disease: >50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal node for PDs or nonresponders, appearance of any new lesion during or at the end of therapy.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Disease-free Survival
Description
Disease-free survival is measured from the date of CR or CRu to date of relapse or death
Time Frame
10 years
Title
Overall Survival
Description
Overall Survival is measured from the first day of chemotherapy until death from any cause.
Time Frame
10 years
Title
Overall Response
Description
Percent of subjects who achieved a complete response (CR) or partial response (PR) any time during the treatment period. CR = complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. PR = >/= 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. No increase should be observed in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter. Except splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. Patients who achieve a CR by the above criteria, but who have persistent morphologic bone marrow involvement will be considered partial responders. No new sites of disease should be observed.
Time Frame
up to 1 year
Title
Secondary Malignancies
Description
The number of patients who develop secondary malignancies including solid tumors, acute leukemia and myelodysplasia or other bone marrow failure syndromes.
Time Frame
10 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Untreated, biopsy proven B-cell non-Hodgkin's lymphoma Age >/= 18 years No other prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for one year. The patient cannot have been exposed to chemotherapy to treat any of these diseases for at least 3 years prior to study entry. Meet staging studies and laboratory tests prior to induction, consolidation and radioimmunotherapy. Exclusion Criteria: Significant medical and/or psychiatric illness which may compromise planned treatment; Pregnant or lactating; HIV-infection. Patients with follicular lymphoma grade 1, 2 or 3A are not eligible for this trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Rizzieri, MD
Organizational Affiliation
Duke Unversity Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Chemotherapy With Monoclonal Antibody and Radioimmunotherapy for High-Risk B-Cell Non-Hodgkins Lymphoma

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