Combination Chemotherapy With or Without Rituximab in Treating Participants With Stage III-IV Classic Hodgkin Lymphoma
Primary Purpose
Classic Hodgkin Lymphoma, Lugano Classification Stage III Hodgkin Lymphoma AJCC v8, Lugano Classification Stage IV Hodgkin Lymphoma AJCC v8
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bleomycin
Dacarbazine
Doxorubicin Hydrochloride
Rituximab
Vinblastine
Sponsored by
About this trial
This is an interventional treatment trial for Classic Hodgkin Lymphoma
Eligibility Criteria
Inclusion Criteria:
- Previously untreated patient with classical Hodgkin's lymphoma patients with stage III and IV
- International Prognostic Score of > 2 (patient must have > 2 of the following risk features: Male, >= 45 years of age, stage IV, albumin < 4, white blood cell count [WBC] >= 15, lymphocytes < 8% or < 600, hemoglobin [Hgb] < 10.5)
- Must sign a consent form
- Absolute neutrophil count (ANC) >= 1,500/microL
- Platelet > 100,000/microL
- Left ventricular ejection fraction (LVEF) >= 50% by multigated acquisition (MUGA) scan or echocardiogram
- Serum creatinine < 2 mg/dl
- Serum bilirubin < 2 mg/dl
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2 x upper limit of normal (ULN)
- Bi-dimensionally measurable disease
Exclusion Criteria:
- Lymphocyte predominant Hodgkin's lymphoma
- Known human immunodeficiency virus (HIV) infection
- Pregnant women and women of child bearing age who are not practicing adequate contraception
- Prior chemotherapy or radiation therapy
- Severe pulmonary disease as judged by the principal investigator (PI) including chronic obstructive pulmonary disease (COPD) and asthma
- Active infection requiring treatment with intravenous therapy
- Presence of central nervous system (CNS) lymphoma
- Concomitant malignancies or previous malignancies within the last 5 years (exception made for adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of cervix)
- Active hepatitis B or C infection
Sites / Locations
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- Rush University Medical Center
- Memorial Sloan Kettering Cancer Center
- M D Anderson Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Arm A (rituximab, combination chemotherapy)
Arm B (combination chemotherapy)
Arm Description
Participants receive rituximab intravenously IV over 7 hours on days 1, 8, 15, and 22 of course 1 and on days 1 and 8 of course 2. Participants also receive doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine IV over 1 hour on days 1 and 15. Treatment with ABVD repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Participants receive doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine as in Arm A.
Outcomes
Primary Outcome Measures
Event-free Survival (EFS) Rate
EFS will be estimated using the Kaplan-Meier method. The log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model will be utilized to include multiple covariates in the time-to-event analysis. Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate.
Secondary Outcome Measures
Full Information
NCT ID
NCT00654732
First Posted
April 3, 2008
Last Updated
February 17, 2020
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00654732
Brief Title
Combination Chemotherapy With or Without Rituximab in Treating Participants With Stage III-IV Classic Hodgkin Lymphoma
Official Title
A Randomized Phase II Study of Rituximab With ABVD Versus Standard ABVD for Patients With Advanced-Stage Classical Hodgkin Lymphoma With Poor Risk Features (IPS Score > 2)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
March 19, 2008 (Actual)
Primary Completion Date
September 5, 2018 (Actual)
Study Completion Date
September 5, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This phase II trial studies how well combination chemotherapy with or without rituximab works in treating participants with stage III-IV classic Hodgkin lymphoma. Monoclonal antibodies, such as rituximab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving rituximab with combination chemotherapy may work better in treating participants with classic Hodgkin lymphoma.
Detailed Description
PRIMARY OBJECTIVES:
I. To evaluate the event free survival (EFS) following therapy with rituximab plus adriamycin (doxorubicin hydrochloride), bleomycin, vinblastine, and dacarbazine (ABVD) or standard ABVD in patients with newly diagnosed classical Hodgkin lymphoma who have poor prognosis defined as International prognostic score (IPS) of > 2.
SECONDARY OBJECTIVES:
I. To compare the effect of the two treatment arms on positron emission tomography (PET) scan results after 2 cycles of therapy.
II. To compare the effect of the two treatment arms on the level of circulating malignant Hodgkin stem cells.
OUTLINE: Participants are randomized to 1 of 2 arms.
ARM A: Participants receive rituximab intravenously (IV) over 7 hours on days 1, 8, 15, and 22 of course 1 and on days 1 and 8 of course 2. Participants also receive doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine IV over 1 hour on days 1 and 15. Treatment with ABVD repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
ARM B: Participants receive doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine as in Arm A.
After completion of study treatment, participants are followed up every 3 months for the first year, every 4 months for the second year, every 6 months for years 3-5, and then annually thereafter.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Classic Hodgkin Lymphoma, Lugano Classification Stage III Hodgkin Lymphoma AJCC v8, Lugano Classification Stage IV Hodgkin Lymphoma AJCC v8
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
58 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A (rituximab, combination chemotherapy)
Arm Type
Experimental
Arm Description
Participants receive rituximab intravenously IV over 7 hours on days 1, 8, 15, and 22 of course 1 and on days 1 and 8 of course 2. Participants also receive doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine IV over 1 hour on days 1 and 15. Treatment with ABVD repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Arm Title
Arm B (combination chemotherapy)
Arm Type
Active Comparator
Arm Description
Participants receive doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine as in Arm A.
Intervention Type
Drug
Intervention Name(s)
Bleomycin
Other Intervention Name(s)
BLEO, BLM
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Dacarbazine
Other Intervention Name(s)
4-(Dimethyltriazeno)imidazole-5-carboxamide, 5-(Dimethyltriazeno)imidazole-4-carboxamide, Asercit, Biocarbazine, Dacarbazina, Dacarbazina Almirall, Dacarbazine - DTIC, Dacatic, Dakarbazin, Deticene, Detimedac, DIC, Dimethyl (triazeno) imidazolecarboxamide, Dimethyl Triazeno Imidazol Carboxamide, Dimethyl Triazeno Imidazole Carboxamide, dimethyl-triazeno-imidazole carboxamide, Dimethyl-triazeno-imidazole-carboximide, DTIC, DTIC-Dome, Fauldetic, Imidazole Carboxamide, Imidazole Carboxamide Dimethyltriazeno, WR-139007
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Doxorubicin Hydrochloride
Other Intervention Name(s)
5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, hydroxydaunorubicin, Rubex
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Rituximab
Other Intervention Name(s)
ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, RTXM83
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Vinblastine
Other Intervention Name(s)
Vincaleucoblastine, VLB
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Event-free Survival (EFS) Rate
Description
EFS will be estimated using the Kaplan-Meier method. The log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model will be utilized to include multiple covariates in the time-to-event analysis. Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate.
Time Frame
From the start of study treatment up to 3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Previously untreated patient with classical Hodgkin's lymphoma patients with stage III and IV
International Prognostic Score of > 2 (patient must have > 2 of the following risk features: Male, >= 45 years of age, stage IV, albumin < 4, white blood cell count [WBC] >= 15, lymphocytes < 8% or < 600, hemoglobin [Hgb] < 10.5)
Must sign a consent form
Absolute neutrophil count (ANC) >= 1,500/microL
Platelet > 100,000/microL
Left ventricular ejection fraction (LVEF) >= 50% by multigated acquisition (MUGA) scan or echocardiogram
Serum creatinine < 2 mg/dl
Serum bilirubin < 2 mg/dl
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2 x upper limit of normal (ULN)
Bi-dimensionally measurable disease
Exclusion Criteria:
Lymphocyte predominant Hodgkin's lymphoma
Known human immunodeficiency virus (HIV) infection
Pregnant women and women of child bearing age who are not practicing adequate contraception
Prior chemotherapy or radiation therapy
Severe pulmonary disease as judged by the principal investigator (PI) including chronic obstructive pulmonary disease (COPD) and asthma
Active infection requiring treatment with intravenous therapy
Presence of central nervous system (CNS) lymphoma
Concomitant malignancies or previous malignancies within the last 5 years (exception made for adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of cervix)
Active hepatitis B or C infection
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hun Lee
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Miami Miller School of Medicine-Sylvester Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center Website
Learn more about this trial
Combination Chemotherapy With or Without Rituximab in Treating Participants With Stage III-IV Classic Hodgkin Lymphoma
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