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

Dose-Intensive Chemotherapy Combined With Monoclonal Antibody Therapy and Targeted Radioimmunotherapy for Untreated Patients With High-Risk B-Cell Non-Hodgkin's Lymphoma

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).

Study Overview

• Status: Completed
• Conditions: Lymphoma, B-Cell
• Intervention / Treatment: Drug: cyclophosphamide; Drug: etoposide; Drug: rituximab; Drug: cytarabine; Drug: doxorubicin; Drug: tositumomab

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

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

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:

• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

Drug: cyclophosphamide; 1.5g/m2 IV over 1 hour on days 1-4 of induction for a total dose of 6.0g/m2; Other Names: Cytoxan®; Drug: etoposide; 300mg/m2 IV over 1 hour every 12 on days 1-3 of induction for a total dose of 1.8 g/m2.; Other Names: VP-16; Drug: rituximab; 375mg/m2 each week x 4 weeks of induction, beginning on day 1; Other Names: Rituxan; Drug: cytarabine; 3g/m2 IV over 1 hour every 12 during consolidation for a total of 8 doses; Other Names: Ara-C; Drug: doxorubicin; 45mg/m2/day IV over 30 minutes on days 1, 2, 3 during consolidation; Other Names: Adriamycin; Drug: tositumomab; 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.; Other Names: Bexxar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free Survival	Disease-free survival is measured from the date of CR or CRu to date of relapse or death	10 years
Overall Survival	Overall Survival is measured from the first day of chemotherapy until death from any cause.	10 years
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.	up to 1 year
Secondary Malignancies	The number of patients who develop secondary malignancies including solid tumors, acute leukemia and myelodysplasia or other bone marrow failure syndromes.	10 years

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: David Rizzieri, MD, Duke Unversity Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2005
• Primary Completion (Actual): April 8, 2012
• Study Completion (Actual): November 3, 2016

Study Registration Dates

• First Submitted: December 18, 2007
• First Submitted That Met QC Criteria: December 18, 2007
• First Posted (Estimate): December 20, 2007

Study Record Updates

• Last Update Posted (Actual): May 30, 2017
• Last Update Submitted That Met QC Criteria: April 19, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: NHL; Bexxar; high dose chemotherapy; high risk non-hodgkins lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Cyclophosphamide; Etoposide; Rituximab; Doxorubicin; Cytarabine
• Other Study ID Numbers: Pro00007096; GSK-103421 (Other Grant/Funding Number: GSK); 5762 (DUMC old IRB #)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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