Rituxan+BEAM: Rituxan + BEAM and Auto Stem Cell Transplant for High Risk Lymphoma or Hodgkin's Disease

Sponsor
Baylor College of Medicine (Other)
Overall Status
Completed
CT.gov ID
NCT01702961
Collaborator
The Methodist Hospital Research Institute (Other), Center for Cell and Gene Therapy, Baylor College of Medicine (Other)
75
Enrollment
2
Locations
1
Arm
175
Duration (Months)
37.5
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

High-dose chemotherapy followed by autologous (the patient's own) peripheral blood (circulating blood) stem cell (cells that divide to form white cells, red cells and cells that help clot) transplantation is a conventional treatment for patients with lymphoma (cancer of lymph glands) and Hodgkin's disease (cancer of lymph glands) after first relapse (recurrence of disease). For patients who did not have a complete response after traditional chemotherapy, the chance is high that the tumor will return even after high-dose chemotherapy. To improve the response and decrease the chance of relapse, doctors have used rituximab, an antibody that kills lymphoma cells, both before and after transplantation. These doctors have reported that more patients had control of the tumor for an extended period of time using rituximab with high-dose chemotherapy with autologous stem cell transplantation. How widely this is applicable is not known.

The purpose of this clinical research trial is to confirm that there is a good control of tumor in patients with lymphoma or Hodgkin's disease treated with rituximab and conventional stem cell transplantation.

Condition or DiseaseIntervention/TreatmentPhase
N/A

Detailed Description

Subjects will receive the chemotherapy through a plastic tube (catheter) placed into a vein under the collarbone. The antibody rituximab is given on the day of admission. The subject will also start a six-day course of chemotherapy at that time. The chemotherapy will consist of the following drugs: BCNU, etoposide also called VP-16, Ara-C also called cytosine arabinoside, and melphalan. BCNU is given on the first day, Ara-C and VP-16 on the second, third, fourth and fifth days, and melphalan on the sixth day. The infusion of blood stem cells is given through the catheter the day after the last dose of chemotherapy. This is called Day 0. A week later the subject will receive shots under the skin of Neupogen to help the stem cells grow quickly. Three additional doses of rituximab are given weekly starting 2 weeks later. If the subject recovers and is discharged from the hospital before getting all the doses of rituximab, they can receive the remainder in clinic.

Patients will remain in the hospital for approximately 3-4 weeks, and in the Houston area for about 30 days from the infusion of the donor cells. The patient will have blood, urine, bone marrow, and x-ray examinations performed as necessary to monitor the results of treatment. They will have blood tests daily while hospitalized.

As an outpatient, the patient will be monitored to make sure their immune system (system in the body that helps protect the body and fights bacterial, viral and fungal infections) is recovering, and the patient may require additional infusions of immunoglobulins (infection-fighting blood proteins) until the blood protein levels are safe. The patient will also be taking antibiotic pills for about 6 months to prevent infections. They will have x-rays and other diagnostic tests (PET scans) every 6-12 months during the next 5 years to make sure the tumor stays under control.

Study Design

Study Type:
Interventional
Actual Enrollment :
75 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Current Practice Study of Rituxan in Patient Receiving BEAM Chemotherapy and Autologous Blood Stem Cell Transplantation for High Risk Lymphoma or Hodgkin's Disease
Study Start Date :
Jun 1, 2002
Actual Primary Completion Date :
Aug 1, 2014
Actual Study Completion Date :
Jan 1, 2017

Arms and Interventions

ArmIntervention/Treatment
Other: BEAM+R: Autologous Stem Cell Transplant

Ara-C, VP-16, BCNU, Melphalan, Rituxan and Stem Cells

Drug: Melphalan
Given on Day -1 Melphalan is administered according to the current SOP.
Other Names:
  • Alkeran
  • Drug: Ara-C
    200 mg/m2 IB BID given on Days -5, -4, -3, -2
    Other Names:
  • Cytarabine
  • Cytosar-u
  • Drug: VP-16
    200 mg/m2 IV BID given on Days -5, -4, -3, -2
    Other Names:
  • Etoposide
  • Drug: BCNU
    BCNU 300 mg/m2 IV given on Day -6
    Other Names:
  • Carmustine
  • Drug: Rituxan
    375 mg/m2 IB given on Days -6, +14, +21, +28
    Other Names:
  • Rituxamib
  • Drug: Stem Cells
    Stem cells given on Day 0
    Other Names:
  • Autologous Blood Stem Cells
  • Outcome Measures

    Primary Outcome Measures

    1. Disease-free Survival [12 months post-transplant]

      Disease-free survival at 12 months post-transplant in patients with Hodgkin's disease or non-Hodgkin's lymphomas

    Secondary Outcome Measures

    1. Median Days to Neutrophil Engraftment [30 days post-transplant]

      Neutrophil engraftment was recorded as the first day that absolute neutrophil counts (ANC) exceeds 0.5 X 10^9/L for three consecutive readings.

    2. Number of Participants With Overall Best Response Achieved After Transplantation [3 months post-transplant]

      Response was summarized as complete remission (CR): disappearance of all evidence of disease; partial remission (PR): regression of measurable disease (>=50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses) and no new sites; stable disease (SD): failure to attain CR/PR/PD; relapsed disease or progressive disease (PD): any new lesion or increase by >= 50% of previously involved sites from nadir.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients with biopsy-proven, relapsed, or refractory CD20+ lymphoma, or HD.

    • At least 2e6 CD34+/kg autologous PBSC stored. If patients are non-mobilizers, then at least 2e8 TNC/kg autologous marrow should be stored.

    • Patient is not pregnant.

    • Zubrod performance status less than or equal to 2.

    • Life expectancy is not severely limited by concomitant illness.

    • Left ventricular ejection fraction greater than or equal to 50%.

    • No uncontrolled arrhythmias or symptomatic cardiac disease.

    • FEV1, FVC and DLCO greater than or equal to 50%.

    • No symptomatic pulmonary disease.

    • Serum creatinine less than or equal to 1.5 mg/dL.

    • Serum bilirubin less than or equal to 2X upper limit of normal, SGPT less than or equal to 3X upper limit of normal.

    • No evidence of chronic active hepatitis or cirrhosis.

    • No effusion or ascites greater than or equal to 1L prior to drainage.

    • HIV negative.

    • Patient or guardian able to sign informed consent.

    • Patients of any age may be enrolled on this protocol.

    Exclusion Criteria:
    • Anyone not meeting the above criteria.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Texas Children's HospitalHoustonTexasUnited States77030
    2The Methodist HospitalHoustonTexasUnited States77030

    Sponsors and Collaborators

    • Baylor College of Medicine
    • The Methodist Hospital Research Institute
    • Center for Cell and Gene Therapy, Baylor College of Medicine

    Investigators

    • Principal Investigator: George Carrum, MD, Associate Professor; Director-Adult Outpatient Clinic

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    George Carrum, Associate Professor; Director-Adult Outpatient Clinic, Baylor College of Medicine
    ClinicalTrials.gov Identifier:
    NCT01702961
    Other Study ID Numbers:
    • H-11892
    • Rituxan+BEAM
    First Posted:
    Oct 10, 2012
    Last Update Posted:
    Dec 19, 2018
    Last Verified:
    Nov 1, 2018
    Keywords provided by George Carrum, Associate Professor; Director-Adult Outpatient Clinic, Baylor College of Medicine
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleRituxan+BEAM: Autologous Stem Cell Transplant
    Arm/Group DescriptionAra-C, VP-16, BCNU, Melphalan, Rituxan and Stem Cells BEAM Conditioning. Melphalan: Given on Day -1 Melphalan is administered according to the current SOP. Ara-C: 200 mg/m2 IB BID given on Days -5, -4, -3, -2 VP-16: 200 mg/m2 IV BID given on Days -5, -4, -3, -2 BCNU: BCNU 300 mg/m2 IV given on Day -6 Rituxan: 375 mg/m2 IB given on Days -6, +14, +21, +28 Stem Cells: Stem cells given on Day 0
    Period Title: Overall Study
    STARTED75
    COMPLETED28
    NOT COMPLETED47

    Baseline Characteristics

    Arm/Group TitleRituxan+BEAM: Autologous Stem Cell Transplant
    Arm/Group DescriptionAra-C, VP-16, BCNU, Melphalan, Rituxan and Stem Cells BEAM Conditioning. Melphalan: Given on Day -1 Melphalan is administered according to the current SOP. Ara-C: 200 mg/m2 IB BID given on Days -5, -4, -3, -2 VP-16: 200 mg/m2 IV BID given on Days -5, -4, -3, -2 BCNU: BCNU 300 mg/m2 IV given on Day -6 Rituxan: 375 mg/m2 IB given on Days -6, +14, +21, +28 Stem Cells: Stem cells given on Day 0
    Overall Participants75
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    53
    Sex: Female, Male (Count of Participants)
    Female
    32
    42.7%
    Male
    43
    57.3%
    Disease at diagnosis (participants) [Number]
    Hodgkin's Disease
    25
    33.3%
    Non-Hodgkin's Lymphoma
    50
    66.7%

    Outcome Measures

    1. Primary Outcome
    TitleDisease-free Survival
    DescriptionDisease-free survival at 12 months post-transplant in patients with Hodgkin's disease or non-Hodgkin's lymphomas
    Time Frame12 months post-transplant

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleBEAM + R: Autologous Stem Cell Transplant
    Arm/Group DescriptionAra-C, VP-16, BCNU, Melphalan, Rituxan and Stem Cells BEAM Conditioning. Melphalan: Given on Day -1 Melphalan is administered according to the current SOP. Ara-C: 200 mg/m2 IB BID given on Days -5, -4, -3, -2 VP-16: 200 mg/m2 IV BID given on Days -5, -4, -3, -2 BCNU: BCNU 300 mg/m2 IV given on Day -6 Rituxan: 375 mg/m2 IB given on Days -6, +14, +21, +28 Stem Cells: Stem cells given on Day 0
    Measure Participants75
    All patients
    76
    Hodgkin's Disease
    88
    Non-Hodgkin's Lymphomas
    70
    2. Secondary Outcome
    TitleMedian Days to Neutrophil Engraftment
    DescriptionNeutrophil engraftment was recorded as the first day that absolute neutrophil counts (ANC) exceeds 0.5 X 10^9/L for three consecutive readings.
    Time Frame30 days post-transplant

    Outcome Measure Data

    Analysis Population Description
    All of the participants enrolled in the study engrafted.
    Arm/Group TitleBEAM + R: Autologous Stem Cell Transplant
    Arm/Group DescriptionAra-C, VP-16, BCNU, Melphalan, Rituxan and Stem Cells BEAM Conditioning. Melphalan: Given on Day -1 Melphalan is administered according to the current SOP. Ara-C: 200 mg/m2 IB BID given on Days -5, -4, -3, -2 VP-16: 200 mg/m2 IV BID given on Days -5, -4, -3, -2 BCNU: BCNU 300 mg/m2 IV given on Day -6 Rituxan: 375 mg/m2 IB given on Days -6, +14, +21, +28 Stem Cells: Stem cells given on Day 0
    Measure Participants75
    Median (Full Range) [days]
    11
    3. Secondary Outcome
    TitleNumber of Participants With Overall Best Response Achieved After Transplantation
    DescriptionResponse was summarized as complete remission (CR): disappearance of all evidence of disease; partial remission (PR): regression of measurable disease (>=50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses) and no new sites; stable disease (SD): failure to attain CR/PR/PD; relapsed disease or progressive disease (PD): any new lesion or increase by >= 50% of previously involved sites from nadir.
    Time Frame3 months post-transplant

    Outcome Measure Data

    Analysis Population Description
    Analysis comprised of all participants who received standard BEAM chemotherapy and adjuvant rituximab while undergoing autologous blood stem cell transplantation for high-risk lymphoma or Hodgkin's disease.
    Arm/Group TitleBEAM + R: Autologous Stem Cell Transplant
    Arm/Group DescriptionAra-C, VP-16, BCNU, Melphalan, Rituxan and Stem Cells BEAM Conditioning. Melphalan: Given on Day -1 Melphalan is administered according to the current SOP. Ara-C: 200 mg/m2 IB BID given on Days -5, -4, -3, -2 VP-16: 200 mg/m2 IV BID given on Days -5, -4, -3, -2 BCNU: BCNU 300 mg/m2 IV given on Day -6 Rituxan: 375 mg/m2 IB given on Days -6, +14, +21, +28 Stem Cells: Stem cells given on Day 0
    Measure Participants75
    Complete Remission (CR)
    63
    84%
    Partial Remission (PR)
    8
    10.7%
    Stable Disease (SD)
    0
    0%
    Relapsed Disease or Progressive Disease (PD)
    4
    5.3%

    Adverse Events

    Time FrameAdverse events related to the study drug, rituximab, are reported during the period of 30 days after transplant.
    Adverse Event Reporting Description Only related adverse events were collected for this study.
    Arm/Group TitleRituxan+BEAM: Autologous Stem Cell Transplant
    Arm/Group DescriptionAra-C, VP-16, BCNU, Melphalan, Rituxan and Stem Cells BEAM Conditioning. BEAM Conditioning. Melphalan: Given on Day -1 Melphalan is administered according to the current SOP. Ara-C: 200 mg/m2 IB BID given on Days -5, -4, -3, -2 VP-16: 200 mg/m2 IV BID given on Days -5, -4, -3, -2 BCNU: BCNU 300 mg/m2 IV given on Day -6 Rituxan: 375 mg/m2 IB given on Days -6, +14, +21, +28 Stem Cells: Stem cells given on Day 0
    All Cause Mortality
    Rituxan+BEAM: Autologous Stem Cell Transplant
    Affected / at Risk (%)# Events
    Total/ (NaN)
    Serious Adverse Events
    Rituxan+BEAM: Autologous Stem Cell Transplant
    Affected / at Risk (%)# Events
    Total1/75 (1.3%)
    Infections and infestations
    Infection (documented clinically or microbiologically) with grade 3 or 4 neutropenia1/75 (1.3%) 1
    Other (Not Including Serious) Adverse Events
    Rituxan+BEAM: Autologous Stem Cell Transplant
    Affected / at Risk (%)# Events
    Total2/75 (2.7%)
    Cardiac disorders
    Cardiovascular/ General - Other1/75 (1.3%) 1
    Gastrointestinal disorders
    Stomatitis/pharyngitis (oral/pharyngeal mucositis)1/75 (1.3%) 1
    General disorders
    Pain - Other1/75 (1.3%) 1
    Infections and infestations
    Infection without neutropenia1/75 (1.3%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleGeorge Carrum, MD
    OrganizationBaylor College of Medicine
    Phone
    EmailGCarrum@houstonmethodist.org
    Responsible Party:
    George Carrum, Associate Professor; Director-Adult Outpatient Clinic, Baylor College of Medicine
    ClinicalTrials.gov Identifier:
    NCT01702961
    Other Study ID Numbers:
    • H-11892
    • Rituxan+BEAM
    First Posted:
    Oct 10, 2012
    Last Update Posted:
    Dec 19, 2018
    Last Verified:
    Nov 1, 2018