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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00577629
First received: December 18, 2007
Last updated: May 20, 2014
Last verified: March 2014
  Purpose

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).


Condition Intervention Phase
Lymphoma, B-Cell
Drug: cyclophosphamide
Drug: etoposide
Drug: rituximab
Drug: cytarabine
Drug: doxorubicin
Drug: tositumomab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • 1 Year Progression-free Survival Rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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 in Patients With a Complete Response (CR or CRu) [ Time Frame: 10 years ] [ Designated as safety issue: No ]
    Disease-free survival is measured from the date of CR or CRu to date of relapse or death

  • Overall Survival [ Time Frame: 10 years ] [ Designated as safety issue: No ]
    Overall Survival is measured from the first day of chemotherapy until death from any cause.

  • Overall Response [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]

    Number 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 =

    1. >/= 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses.
    2. No increase should be observed in the size of other nodes, liver, or spleen.
    3. Splenic and hepatic nodules must regress by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter.
    4. Except splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present.
    5. Patients who achieve a CR by the above criteria, but who have persistent morphologic bone marrow involvement will be considered partial responders.
    6. No new sites of disease should be observed.

  • Secondary Malignancies [ Time Frame: 10 years ] [ Designated as safety issue: Yes ]
    The number of patients who develop a secondary malignancies including solid tumors, acute leukemia and myelodysplasia or other bone marrow failure syndromes.


Enrollment: 39
Study Start Date: June 2005
Estimated Study Completion Date: February 2021
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Induction + Consolidation + Bexxar
Induction:Cyclophosphamide, Etoposide, and Rituxan followed by Consolidation:Cytarabine and Doxorubicin followed by radioimmunotherapy:Bexxar
Drug: cyclophosphamide
1.5g/m2 IV over 1 hour on days 1-4 of induction for a total dose of 6.0g/m2
Other Name: 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 Name: VP-16
Drug: rituximab
375mg/m2 each week x 4 weeks of induction, beginning on day 1
Other Name: Rituxan
Drug: cytarabine
3g/m2 IV over 1 hour every 12 during consolidation for a total of 8 doses
Other Name: Ara-C
Drug: doxorubicin
45mg/m2/day IV over 30 minutes on days 1, 2, 3 during consolidation
Other Name: 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 Name: Bexxar

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00577629

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
GlaxoSmithKline
Investigators
Principal Investigator: David Rizzieri, MD Duke Unversity Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00577629     History of Changes
Other Study ID Numbers: Pro00007096, GSK-103421, 5762
Study First Received: December 18, 2007
Results First Received: March 4, 2013
Last Updated: May 20, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
high risk non-hodgkins lymphoma
NHL
Bexxar
high dose chemotherapy

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Antibodies, Monoclonal
Cyclophosphamide
Cytarabine
Doxorubicin
Etoposide
Liposomal doxorubicin
Alkylating Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists

ClinicalTrials.gov processed this record on November 20, 2014