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Combination Chemotherapy With or Without Rituximab in Treating Participants With Stage III-IV Classic Hodgkin Lymphoma

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ClinicalTrials.gov Identifier: NCT00654732
Recruitment Status : Completed
First Posted : April 9, 2008
Last Update Posted : November 19, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
Classic Hodgkin Lymphoma Lugano Classification Stage III Hodgkin Lymphoma AJCC v8 Lugano Classification Stage IV Hodgkin Lymphoma AJCC v8 Drug: Bleomycin Drug: Dacarbazine Drug: Doxorubicin Hydrochloride Biological: Rituximab Drug: Vinblastine Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 58 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : March 19, 2008
Actual Primary Completion Date : September 5, 2018
Actual Study Completion Date : September 5, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Rituximab

Arm Intervention/treatment
Experimental: Arm A (rituximab, combination chemotherapy)
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.
Drug: Bleomycin
Given IV
Other Names:
  • BLEO
  • BLM

Drug: Dacarbazine
Given IV
Other Names:
  • 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

Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • 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

Biological: Rituximab
Given IV
Other Names:
  • 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

Drug: Vinblastine
Given IV
Other Names:
  • Vincaleucoblastine
  • VLB

Active Comparator: Arm B (combination chemotherapy)
Participants receive doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine as in Arm A.
Drug: Bleomycin
Given IV
Other Names:
  • BLEO
  • BLM

Drug: Dacarbazine
Given IV
Other Names:
  • 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

Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • 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

Drug: Vinblastine
Given IV
Other Names:
  • Vincaleucoblastine
  • VLB




Primary Outcome Measures :
  1. Event-free survival (EFS) rate [ Time Frame: From the start of study treatment up to 3 years ]
    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 :
  1. Overall survival (OS) [ Time Frame: From the start of study treatment up to 39 months after completion of study treatment ]
    OS 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.

  2. Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: Up to 39 months after completion of study treatment ]
    Toxicity data will be summarized by frequency tables. The association between the types and severity of toxicity and the treatment groups will be evaluated. No formal statistical testing will be performed on these summary data.

  3. CD19 and CD20 biomarker analysis [ Time Frame: Up to 39 months after completion of study treatment ]
    Expression of CD19 and CD20 will be measured over time. The distribution of biomarkers will be examined first by the exploratory data analysis using scatter plot matrix, box plots, BLiP plot (Lee, 1997) and trellis plot, etc. Correlation among continuous biomarkers will be examined by Pearson or Spearman rank correlation coefficients. The association on discrete biomarkers will be tested by chi-square or Fisher's exact test. McNemar's test will be applied to test the change of a single discrete biomarker over time. Repeated measures analysis including mixed effects model will be performed to analyze biomarkers change over time.



Information from the National Library of Medicine

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Ages Eligible for Study:   17 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00654732


Locations
United States, Florida
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States, 33136
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Hun Lee M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00654732     History of Changes
Other Study ID Numbers: 2007-0144
NCI-2018-01855 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2007-0144 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: April 9, 2008    Key Record Dates
Last Update Posted: November 19, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Lymphoma
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies
Immunoglobulins
Rituximab
Antibodies, Monoclonal
Liposomal doxorubicin
Doxorubicin
Bleomycin
Vinblastine
Dacarbazine
Imidazole
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Antirheumatic Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents