Combination Chemotherapy and Rituximab With Pegfilgrastim Followed by Rituximab, in Large B-Cell Non-Hodgkin's Lymphoma

Sponsor
SCRI Development Innovations, LLC (Other)
Overall Status
Completed
CT.gov ID
NCT00193479
Collaborator
Genentech, Inc. (Industry), Amgen (Industry)
51
2
1
82.1
25.5
0.3

Study Details

Study Description

Brief Summary

The purposes of this trial are to decrease toxicity and improve treatment effectiveness elderly patients. With a short course of chemotherapy with cyclophosphamide, mitoxantrone, vincristine, and prednisone with concurrent administration of rituximab it is likely to be as effective as longer programs, and will certainly be better tolerated by this patient group. The addition of maintenance therapy may result in substantial prolongation of remission duration.

Detailed Description

Upon determination of eligibility, patients will receive:
  • Cyclophosphamide + Mitoxantrone + Vincristine + Prednisone + Rituximab

Patients that are not considered candidates for anthracycline therapy will not receive mitoxantrone. Patients with objective response (partial or complete response) or stable disease will receive Rituximab maintenance therapy.

Study Design

Study Type:
Interventional
Actual Enrollment :
51 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Trial of Brief Duration Combination Chemotherapy and Rituximab With Prophylactic Pegfilgrastim, Followed by Maintenance Rituximab, in Elderly/Poor Performance Status Patients With Large B-Cell Non-Hodgkin's Lymphoma
Study Start Date :
Apr 1, 2003
Actual Primary Completion Date :
Jul 1, 2008
Actual Study Completion Date :
Feb 1, 2010

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cyclophosphamide/Vincristine/Rituximab +/- Mitoxantrone

All patients receive three courses of combination chemotherapy/rituximab followed by pegfilgrastim, administered at 21-day intervals. Treatment administered is as follows: cyclophosphamide 500mg/m2 IV day 1; mitoxantrone 10mg/m2 IV day 1; vincristine 1.0mg/m2 (maximum 2mg) IV day 1; prednisone 80mg PO days 1 - 5; rituximab 375mg/m2 IV day 1.

Drug: Cyclophosphamide
Cyclophosphamide
Other Names:
  • Cytoxan
  • Drug: Mitoxantrone
    Mitoxantrone
    Other Names:
  • Novantrone
  • Drug: Vincristine
    Vincristine
    Other Names:
  • Oncovin
  • Drug: Prednisone
    Prednisone

    Drug: Rituximab
    Rituximab
    Other Names:
  • Rituxan
  • Outcome Measures

    Primary Outcome Measures

    1. Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment [18 Months]

      Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    To be included in this study, you must meet the following criteria:
    • Histologically documented large B-cell, CD20-positive non-Hodgkin's lymphoma

    • No previous treatment

    • Clinical stage II, III, or IV by the Ann Arbor Staging Criteria

    • Age > 70 years

    • ECOG performance status 0, 1, or 2

    • Adequate bone marrow, liver and kidney function

    • Must give written informed consent prior to entering this trial

    Exclusion Criteria:
    You cannot participate in this study if any of the following apply to you:
    • Age < 18 years

    • Central nervous system involvement with lymphoma

    • Coexistent active malignancies treated within five years

    • Active infection precluding the use of combination chemotherapy

    • HIV infection

    • Pregnant or lactating

    Please note: There are additional inclusion/exclusion criteria. The study center will determine if you meet all of the criteria. If you do not qualify for the trial, study personnel will explain the reasons. If you do qualify, study personnel will explain the trial in detail and answer any questions you may have.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Florida Cancer Specialists Fort Myers Florida United States 33901
    2 Tennessee Oncology Nashville Tennessee United States 37203

    Sponsors and Collaborators

    • SCRI Development Innovations, LLC
    • Genentech, Inc.
    • Amgen

    Investigators

    • Principal Investigator: John D. Hainsworth, MD, SCRI Development Innovations, LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    SCRI Development Innovations, LLC
    ClinicalTrials.gov Identifier:
    NCT00193479
    Other Study ID Numbers:
    • SCRI LYM 28
    First Posted:
    Sep 19, 2005
    Last Update Posted:
    Mar 3, 2022
    Last Verified:
    Feb 1, 2022

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Forty-eight of 51 patients (94%) completed the initial three courses of rituximab/chemotherapy. Forty-four of the 48 patients (92%) received the Rituximab maintenance therapy.
    Arm/Group Title CNOP (CVP)/Rituximab/Pegfilgrastim Followed by Rituximab
    Arm/Group Description Cyclophosphamide 500mg/m2 IV day 1; Mitoxantrone 10mg/m2 IV day 1; Vincristine 1.0mg/m2 IV day 1; Prednisone 80mg PO days 1-5; Rituximab 375mg/m2 IV day 1; Pegfilgrastim 6mg SQ, day 2 OR Cyclophosphamide 500mg/m2 IV day 1; Vincristine 1.0mg/m2 IV day 1; Prednisone 80mg PO days 1-5; Rituximab 375mg/m2 IV day 1; Pegfilgrastim 6mg SQ, day 2
    Period Title: Induction Chemotherapy
    STARTED 51
    COMPLETED 48
    NOT COMPLETED 3
    Period Title: Induction Chemotherapy
    STARTED 48
    COMPLETED 44
    NOT COMPLETED 4

    Baseline Characteristics

    Arm/Group Title CNOP (CVP)/Rituximab/Pegfilgrastim Followed by Rituximab
    Arm/Group Description Cyclophosphamide 500mg/m2 IV day 1; Mitoxantrone 10mg/m2 IV day 1; Vincristine 1.0mg/m2 IV day 1; Prednisone 80mg PO days 1-5; Rituximab 375mg/m2 IV day 1; Pegfilgrastim 6mg SQ, day 2 OR Cyclophosphamide 500mg/m2 IV day 1; Vincristine 1.0mg/m2 IV day 1; Prednisone 80mg PO days 1-5; Rituximab 375mg/m2 IV day 1; Pegfilgrastim 6mg SQ, day 2
    Overall Participants 51
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    78
    Sex: Female, Male (Count of Participants)
    Female
    36
    70.6%
    Male
    15
    29.4%
    Region of Enrollment (participants) [Number]
    United States
    51
    100%

    Outcome Measures

    1. Primary Outcome
    Title Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment
    Description Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
    Time Frame 18 Months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title CNOP (CVP)/Rituximab/Pegfilgrastim Followed by Rituximab
    Arm/Group Description Cyclophosphamide 500mg/m2 IV day 1; Mitoxantrone 10mg/m2 IV day 1; Vincristine 1.0mg/m2 IV day 1; Prednisone 80mg PO days 1-5; Rituximab 375mg/m2 IV day 1; Pegfilgrastim 6mg SQ, day 2 OR Cyclophosphamide 500mg/m2 IV day 1; Vincristine 1.0mg/m2 IV day 1; Prednisone 80mg PO days 1-5; Rituximab 375mg/m2 IV day 1; Pegfilgrastim 6mg SQ, day 2
    Measure Participants 48
    Number [percentage of patients]
    81

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title CNOP (CVP)/Rituximab/Pegfilgrastim Followed by Rituximab
    Arm/Group Description Cyclophosphamide 500mg/m2 IV day 1; Mitoxantrone 10mg/m2 IV day 1; Vincristine 1.0mg/m2 IV day 1; Prednisone 80mg PO days 1-5; Rituximab 375mg/m2 IV day 1; Pegfilgrastim 6mg SQ, day 2 OR Cyclophosphamide 500mg/m2 IV day 1; Vincristine 1.0mg/m2 IV day 1; Prednisone 80mg PO days 1-5; Rituximab 375mg/m2 IV day 1; Pegfilgrastim 6mg SQ, day 2
    All Cause Mortality
    CNOP (CVP)/Rituximab/Pegfilgrastim Followed by Rituximab
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    CNOP (CVP)/Rituximab/Pegfilgrastim Followed by Rituximab
    Affected / at Risk (%) # Events
    Total 24/51 (47.1%)
    Cardiac disorders
    Atrial fibrillation 3/51 (5.9%) 3
    CHF 1/51 (2%) 1
    Ventricular tachycardia 1/51 (2%) 1
    Gastrointestinal disorders
    Perforated colon 1/51 (2%) 1
    Fecal incontinence 1/51 (2%) 1
    Gastrointestinal bleed 1/51 (2%) 1
    Diverticulitis 1/51 (2%) 1
    Diverticulosis 2/51 (3.9%) 2
    Intestinal obstruction 1/51 (2%) 1
    Esophagitis 1/51 (2%) 1
    Diarrhea 1/51 (2%) 3
    General disorders
    Fever 1/51 (2%) 1
    Infections and infestations
    Pneumonia 2/51 (3.9%) 2
    Infection of bilateral heel ulcer wounds 1/51 (2%) 1
    Urinary tract infection 2/51 (3.9%) 2
    Cellulitis 2/51 (3.9%) 2
    Metabolism and nutrition disorders
    Tumor lysis syndrome 1/51 (2%) 1
    Hyperglycemia 1/51 (2%) 1
    Musculoskeletal and connective tissue disorders
    Infection, L ankle 1/51 (2%) 1
    Fractured hip 2/51 (3.9%) 2
    Fractured ankle 1/51 (2%) 1
    Acute chronic fractures on lumbar spine 1/51 (2%) 1
    Intractable neck pain 1/51 (2%) 1
    Right lower thigh pain 1/51 (2%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    New primary lung cancer 1/51 (2%) 1
    Nervous system disorders
    CVA 4/51 (7.8%) 4
    Concussion, related to fall 1/51 (2%) 1
    Intramedullary spinal cord mass 1/51 (2%) 1
    Renal and urinary disorders
    Gross hematuria 1/51 (2%) 1
    Skin and subcutaneous tissue disorders
    Acute renal failure 1/51 (2%) 1
    Other (Not Including Serious) Adverse Events
    CNOP (CVP)/Rituximab/Pegfilgrastim Followed by Rituximab
    Affected / at Risk (%) # Events
    Total 51/51 (100%)
    Blood and lymphatic system disorders
    Anemia 35/51 (68.6%) 169
    Leukopenia 25/51 (49%) 82
    Neutropenia 21/51 (41.2%) 54
    Thrombocytopenia 14/51 (27.5%) 59
    Cardiac disorders
    Cardiac Toxicity 8/51 (15.7%) 17
    Hypertension 4/51 (7.8%) 4
    Hypotension 4/51 (7.8%) 6
    Gastrointestinal disorders
    Anorexia 29/51 (56.9%) 85
    Constipation 21/51 (41.2%) 47
    Diarrhea 12/51 (23.5%) 19
    Mucositis 5/51 (9.8%) 8
    Nausea 18/51 (35.3%) 31
    Stomatitis 6/51 (11.8%) 8
    Taste Alteration 3/51 (5.9%) 13
    Vomiting 9/51 (17.6%) 13
    General disorders
    Chills/Rigor 3/51 (5.9%) 4
    Edema 8/51 (15.7%) 18
    Fatigue 44/51 (86.3%) 305
    Fever 8/51 (15.7%) 12
    Insomnia 6/51 (11.8%) 8
    Weakness 13/51 (25.5%) 45
    Infections and infestations
    Infection 19/51 (37.3%) 36
    Metabolism and nutrition disorders
    Hyperglycemia 8/51 (15.7%) 21
    Musculoskeletal and connective tissue disorders
    Arthralgia 13/51 (25.5%) 42
    Myalgia 11/51 (21.6%) 26
    Nervous system disorders
    Dizziness 8/51 (15.7%) 11
    Headache 3/51 (5.9%) 4
    Neuropathy 4/51 (7.8%) 6
    Respiratory, thoracic and mediastinal disorders
    Cough 4/51 (7.8%) 4
    Dyspnea 3/51 (5.9%) 3
    Pulmonary 7/51 (13.7%) 29
    Skin and subcutaneous tissue disorders
    Alopecia 30/51 (58.8%) 152
    Rash/Skin Irritation 8/51 (15.7%) 20

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The sponsor can review/embargo results communications prior to public release for a period that is >60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.

    Results Point of Contact

    Name/Title John D. Hainsworth, MD
    Organization Sarah Cannon Research Institute
    Phone 615-329-7274
    Email jhainsworth@tnonc.com
    Responsible Party:
    SCRI Development Innovations, LLC
    ClinicalTrials.gov Identifier:
    NCT00193479
    Other Study ID Numbers:
    • SCRI LYM 28
    First Posted:
    Sep 19, 2005
    Last Update Posted:
    Mar 3, 2022
    Last Verified:
    Feb 1, 2022