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Trial record 1 of 1 for:    NCT02166463
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Brentuximab Vedotin and Combination Chemotherapy in Treating Children and Young Adults With Stage IIB or Stage IIIB-IVB Hodgkin Lymphoma

This study is currently recruiting participants.
See Contacts and Locations
Verified August 2017 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02166463
First received: June 16, 2014
Last updated: August 14, 2017
Last verified: August 2017
  Purpose
This randomized phase III trial studies brentuximab vedotin and combination chemotherapy to see how well they work compared to combination chemotherapy alone in treating children and young adults with stage IIB or stage IIIB-IVB Hodgkin lymphoma. Combinations of biological substances in brentuximab vedotin may be able to carry cancer-killing substances directly to Hodgkin lymphoma cells. Drugs used in chemotherapy, such as doxorubicin hydrochloride, bleomycin sulfate, vincristine sulfate, etoposide, prednisone, and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known if combination chemotherapy is more effective with or without brentuximab vedotin in treating Hodgkin lymphoma.

Condition Intervention Phase
Childhood Hodgkin Lymphoma Classical Hodgkin Lymphoma Stage IIB Hodgkin Lymphoma Stage IIIB Hodgkin Lymphoma Stage IV Hodgkin Lymphoma Stage IVA Hodgkin Lymphoma Stage IVB Hodgkin Lymphoma Biological: Bleomycin Sulfate Drug: Brentuximab Vedotin Drug: Cyclophosphamide Drug: Doxorubicin Hydrochloride Drug: Etoposide Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Prednisone Other: Quality-of-Life Assessment Other: Questionnaire Administration Drug: Vincristine Sulfate Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Phase 3 Study of Brentuximab Vedotin (SGN-35) for Newly Diagnosed High-Risk Classical Hodgkin Lymphoma (cHL) in Children and Young Adults

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Event free survival (EFS), where events include disease progression or relapse, second malignancy, or death [ Time Frame: Up to 48 months ]
    Primary analysis will be based 1-sided log rank test comparison of EFS curves between the 2 randomized arms per intention-to-treat principle.


Secondary Outcome Measures:
  • Proportion of patients experiencing grade 3+ peripheral neuropathy assessed by modified Balis scale [ Time Frame: After 42 days of chemotherapy ]
    Will be estimated for Bv-AVEPC arm and for ABVE-PC arm along with the corresponding. The proportion will be compared between the 2 arms by two-sample Z test of proportions at 1-sided alpha level of 0.05.

  • Proportion of patients experiencing grade 3+ peripheral neuropathy assessed by modified Balis scale [ Time Frame: After 105 days of chemotherapy ]
    Will be estimated for Bv-AVEPC arm and for ABVE-PC arm along with the corresponding 95% confidence intervals. The proportion will be compared between the 2 arms by two-sample Z test of proportions at 1-sided alpha level of 0.05.

  • Proportion of patients needing protocol-directed radiation therapy (RT) defined as patients with slow responding lesions (SRL) or progressive disease (PD) [ Time Frame: After 42 days of chemotherapy ]
    The proportion of patients needing protocol radiation therapy (RT) (including PD) will be compared between the two arms to see if Bv-AVEPC arm has a lower rate for RT compared to ABVE-PC arm. Two-sample Z test of proportions at 1-sided alpha level of 0.05 will be used for these comparisons.

  • Proportion of patients with early response defined as no slow responding lesions (SRL) and no progressive disease (PD) at all sites determined by positron emission tomography (PET) per Deauville criteria through central review [ Time Frame: After 42 days of chemotherapy ]
    The proportion of patients with no SRL and no PD will be compared between the two randomized arms to see if brentuximab vedotin in the chemotherapy backbone of doxorubicin hydrochloride, vincristine sulfate, etoposide, prednisone and cyclophosphamide (Bv-AVEPC) arm has a higher rate of early response compared to doxorubicin hydrochloride, bleomycin sulfate, vincristine sulfate, etoposide, prednisone, and cyclophosphamide (ABVE-PC) arm. Two-sample Z test of proportions at 1-sided alpha level of 0.05 will be used for these comparisons.


Other Outcome Measures:
  • Childhood International Prognostic Score (CHIPS) score [ Time Frame: Baseline ]
    CHIPS will be computed for all patients and summarized by descriptive statistics. Will examine the association between CHIPS and early response by cross-tabulations and Chi-square tests within each arm separately, as well as logistic regression model where early response is the outcome variable and CHIPS the predictor variable combining the 2 arms with adjustment for randomized chemotherapy. EFS by CHIPS within each arm and combining both arms will be estimated by Kaplan-Meier curves, and compared by log rank test. Subset analyses and Cox proportional hazards models will also be used.

  • Dose of radiation received by normal tissues for doxorubicin hydrochloride, bleomycin sulfate, vincristine sulfate, etoposide, prednisone, and cyclophosphamide (ABVE-PC) arm [ Time Frame: Up to 48 months ]
    Descriptive statistics will be used to summarize RT doses received by normal tissues on this study. Two-sample t-test will be used to compare the doses received on this study to those on prior studies.

  • Efficacy of Iinvolved site radiotherapy (ISRT) by analyzing the event-free survival of patients treated with response-adapted ISRT and by evaluating patterns of relapse following ISRT [ Time Frame: Up to 3 years ]
    EFS for patients on each arm as well as those receiving ISRT or those with slow early response (SER) on each arm will be estimated. One-sample log rank test will be used to compare the observed EFS to the assumed baseline of 82% at 3 years to see if the observed EFS is significantly lower than the projection in these subsets.

  • Frequency of patients with persistent Deauville score of 3 [ Time Frame: Up to end of course 5 ]
    Will be calculated with corresponding standard deviation. EFS and risk of relapse of patients with or without radiation will be compared at same Deauville score level (2 or 3) and perform Cox multivariate models to include other possible covariates besides of the Deauville score.

  • Pharmacokinetic (PK) analyses [ Time Frame: Pre-dose and end of infusion on day 1, days 2, 3, 8, and 15 of course 4 and pre-dose on day 1 and day 22 of course 5 ]
    PK concentration time profile will be evaluated.


Estimated Enrollment: 600
Actual Study Start Date: March 16, 2015
Estimated Study Completion Date: November 30, 2019
Estimated Primary Completion Date: November 30, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (ABVE-PC)
Patients receive doxorubicin hydrochloride IV over 1-15 minutes on days 1-2, bleomycin sulfate IV over 10 minutes or SC on days 1 and 8, vincristine sulfate IV over 1 minute on days 1 and 8, etoposide IV over 60-120 minutes on days 1-3, prednisone PO BID on days 1-7, and cyclophosphamide IV over 30-60 minutes on days 1 and 2. Treatment repeats every 21 days for 5 courses in the absence of disease progression or unacceptable toxicity.
Biological: Bleomycin Sulfate
Given IV or SC
Drug: Cyclophosphamide
Given IV
Drug: Doxorubicin Hydrochloride
Given IV
Drug: Etoposide
Given IV
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Drug: Prednisone
Given PO
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Drug: Vincristine Sulfate
Given IV
Experimental: ARM II (Bv-AVEPC)
Patients receive brentuximab vedotin IV over 30 minutes on day 1. Patients also receive doxorubicin hydrochloride, etoposide, prednisone, and cyclophosphamide as in Arm I and vincristine sulfate IV over 1 minute on day 8. Treatment repeats every 21 days for 5 courses in the absence of disease progression or unacceptable toxicity.
Drug: Brentuximab Vedotin
Given IV
Drug: Cyclophosphamide
Given IV
Drug: Doxorubicin Hydrochloride
Given IV
Drug: Etoposide
Given IV
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Drug: Prednisone
Given PO
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Drug: Vincristine Sulfate
Given IV

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   2 Years to 22 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with newly diagnosed, pathologically confirmed cHL meeting one of the following Ann Arbor stages are eligible:

    • Stage IIB with bulk
    • Stage IIIB
    • Stage IVA
    • Stage IVB

      • If study eligibility by staging is uncertain, consultation with Imaging and Radiation Oncology Core (IROC) Rhode Island (RI) may be obtained prior to study enrollment
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

    • 2 to < 6 years: male 0.8 mg/dL, female 0.8 mg/dL
    • 6 to < 10 years: male 1 mg/dL, female 1 mg/dL
    • 10 to < 13 years: male 1.2 mg/dL, female 1.2 mg/dL
    • 13 to < 16 years: male 1.5 mg/dL, female 1.4 mg/dL
    • >= 16 years: male 1.7 mg/dL, female 1.4 mg/dL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate transaminase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine transaminase [ALT]) < 2.5 x upper limit of normal (ULN) for age
  • Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by radionuclide angiogram
  • Forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) > 60% by pulmonary function test (PFT), unless due to large mediastinal mass from Hodgkin lymphoma (HL)
  • For children who are unable to cooperate for PFTs, the criteria are: no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry reading of > 92% on room air
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

  • Patients with nodular lymphocyte-predominant HL
  • Patients with an immunodeficiency that existed prior to diagnosis, such as primary immunodeficiency syndromes, organ transplant recipients and children on current systemic immunosuppressive agents are not eligible
  • Patients who are pregnant; (a negative pregnancy test is required for female patients of childbearing potential)
  • Lactating females who plan to breastfeed
  • Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for 30 days after the last dose of chemotherapy
  • Patients known to be positive for human immunodeficiency virus (HIV) are not eligible
  • Patients who have received any previous chemotherapy or radiation therapy are not eligible
  • Patients who received systemic corticosteroids within 28 days of enrollment on this protocol, except as specified, are not eligible
  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: NCT02166463

  Show 185 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Sharon Castellino Children's Oncology Group
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02166463     History of Changes
Other Study ID Numbers: NCI-2014-01223
NCI-2014-01223 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
AHOD1331 ( Other Identifier: Childrens Oncology Group )
AHOD1331 ( Other Identifier: CTEP )
Study First Received: June 16, 2014
Last Updated: August 14, 2017

Additional relevant MeSH terms:
Lymphoma
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Liposomal doxorubicin
Etoposide phosphate
Doxorubicin
Prednisone
Etoposide
Vincristine
Bleomycin
Antibodies, Monoclonal
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 18, 2017