Brentuximab Vedotin and Combination Chemotherapy in Treating Children and Young Adults With Stage IIB, Stage IIIB, IVA, or IVB Hodgkin Lymphoma
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| ClinicalTrials.gov Identifier: NCT02166463 |
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Recruitment Status :
Active, not recruiting
First Posted : June 18, 2014
Results First Posted : May 31, 2023
Last Update Posted : December 21, 2023
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Sponsor:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
National Cancer Institute (NCI)
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Brief Summary:
This 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 with bulk, stage IIIB, IVA, or IVB Hodgkin lymphoma. Combinations of biological substances in brentuximab vedotin may be able to carry cancer-killing substances directly to Hodgkin lymphoma cells. Chemotherapy drugs, 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 children with high-risk Hodgkin lymphoma.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Ann Arbor Stage IIB Hodgkin Lymphoma Ann Arbor Stage IIIB Hodgkin Lymphoma Ann Arbor Stage IVA Hodgkin Lymphoma Ann Arbor Stage IVB Hodgkin Lymphoma Childhood Hodgkin Lymphoma Classic Hodgkin Lymphoma | Biological: Bleomycin Sulfate Drug: Brentuximab Vedotin Drug: Cyclophosphamide Drug: Doxorubicin Hydrochloride Drug: Etoposide Other: Laboratory Biomarker Analysis Drug: Methylprednisolone Other: Pharmacological Study Drug: Prednisone Other: Quality-of-Life Assessment Other: Questionnaire Administration Drug: Vincristine Sulfate | Phase 3 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 600 participants |
| 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 |
| Actual Study Start Date : | March 19, 2015 |
| Actual Primary Completion Date : | December 31, 2021 |
| Estimated Study Completion Date : | September 22, 2024 |
Resource links provided by the National Library of Medicine
Drug Information
available for:
Brentuximab vedotin
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Arm I (ABVE-PC)
Patients receive doxorubicin hydrochloride IV over on days 1-2, bleomycin sulfate IV or SC on days 1 and 8, vincristine sulfate IV on days 1 and 8, etoposide IV on days 1-3, prednisone orally PO BID or methylprednisolone IV on days 1-7, and cyclophosphamide IV on days 1 and 2. Treatment repeats every 21 days for 5 cycles in the absence of disease progression or unacceptable toxicity.
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Biological: Bleomycin Sulfate
Given IV or SC
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Drug: Etoposide Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Methylprednisolone Given IV
Other Names:
Other: Pharmacological Study Correlative studies Drug: Prednisone Given PO
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: ARM II (Bv-AVEPC)
Patients receive brentuximab vedotin IV on day 1. Patients also receive doxorubicin hydrochloride, etoposide, prednisone or methylprednisolone, and cyclophosphamide as in Arm I and vincristine sulfate IV on day 8. Treatment repeats every 21 days for 5 cycles in the absence of disease progression or unacceptable toxicity.
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Drug: Brentuximab Vedotin
Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Drug: Etoposide Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Methylprednisolone Given IV
Other Names:
Other: Pharmacological Study Correlative studies Drug: Prednisone Given PO
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies Drug: Vincristine Sulfate Given IV
Other Names:
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Primary Outcome Measures :
- Event Free Survival (EFS), Where Events Include Disease Progression or Relapse, Second Malignancy, or Death [ Time Frame: Up to 48 months after the last enrollment ]Primary analysis will be based 1-sided log rank test comparison of EFS curves between the 2 randomized arms per intention-to-treat principle. Progression is defined as an ≥50% increase of in the product of the perpendicular diameters of any of the involved nodes or nodal masses or focal organ lesions in sites that were persistently PET positive; or recurrent PET positive lesions (Deauville 4, 5) in sites that had previously been PET negative regardless of change of size, as was the development of new PET avid measurable lesion(s) >1.5cm in any axis, or new sites of assessable disease. Relapse is defined in patients who achieved a prior CR but subsequently has an increase of ≥50% of the PPD in prior nodal or extranodal sites in a recurrently PET positive lesion(s), or the development of new measurable lesion(s) >1.5cm in any axis, or new sites of assessable disease. Second malignancy is defined based on report of a cancer that is not considered to be classic Hodgkin Lymphoma.
Secondary Outcome Measures :
- Percentages of Patients With Early Response Defined as no Slow Responding Lesions (SRL) and no Progressive Disease (PD) at Any Disease Sites Determined by Positron Emission Tomography (PET) Per Deauville Criteria Through Central Review [ Time Frame: After 42 days of chemotherapy ]The percentages of patients (with available PET scan) 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.
- Percentages of Patients Experiencing Grade 3+ Peripheral Neuropathy Assessed by Modified Balis Scale [ Time Frame: From the enrollment of the patient to the time of analysis or the last follow-up; an average of 3.6 years. ]The percentages of patients experiencing grade 3+ peripheral neuropathy assessed by the treating clinician using the modified Balis scale. The "Modified Balis scale of Pediatric Neuropathy" allows clinicians to assign a score for sensory or motor neuropathy symptoms separately. Scores range from 1 to 4 with 1 being the least symptomatic state and 4 indicating a severe debility. The percentages of patients (with a score >/=3) will be compared between the 2 arms by two-sample Z test at 1-sided alpha level of 0.05.
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.
- Dose of Radiation Received by Normal Tissues Following Chemotherapy on Either Study 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 Involved 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.
- Risk of Relapse Among RRL Subjects That Have at Least One Lesion That is Deauville 3 at PET 2 [ Time Frame: Up to 48 months after the last enrollment ]The risk of relapse for cases that are RRL, but have Deauville 3 lesions, will be compared to those that are classified as complete metabolic response at PET2 with solely Deauville 1 or 2 lesions with K-sample test.
- Pharmacokinetic (PK) Analyses [ Time Frame: Pre-dose and end of infusion on day 1, days 2, 3, 8, and 15 of cycle 4 and pre-dose on day 1 and day 22 of cycle 5 (each cycle = 21 days) ]PK concentration time profile will be evaluated.
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| Ages Eligible for Study: | 2 Years to 22 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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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
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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
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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 (performed within 14 days prior to enrollment):
- 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 (performed within 14 days prior to enrollment)
- 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 (performed within 14 days prior to enrollment)
- 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; (since fetal toxicities and teratogenic effects have been noted for several of the study drugs, 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
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): NCT02166463
Locations
Show 199 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Sharon M Castellino | Children's Oncology Group |
Study Documents (Full-Text)
Documents provided by National Cancer Institute (NCI):
Documents provided by National Cancer Institute (NCI):
Study Protocol and Statistical Analysis Plan [PDF] June 22, 2020
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT02166463 |
| Other Study ID Numbers: |
NCI-2014-01223 NCI-2014-01223 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) s15-00950 AHOD1331 ( Other Identifier: Children's Oncology Group ) AHOD1331 ( Other Identifier: CTEP ) U10CA180886 ( U.S. NIH Grant/Contract ) |
| First Posted: | June 18, 2014 Key Record Dates |
| Results First Posted: | May 31, 2023 |
| Last Update Posted: | December 21, 2023 |
| Last Verified: | November 2023 |
Additional relevant MeSH terms:
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Lymphoma Hodgkin Disease Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Prednisone Methylprednisolone Methylprednisolone Acetate Methylprednisolone Hemisuccinate Prednisolone Prednisolone acetate Cortisone |
Cyclophosphamide Doxorubicin Liposomal doxorubicin Etoposide Vincristine Etoposide phosphate Brentuximab Vedotin Bleomycin Podophyllotoxin Antineoplastic Agents, Immunological Antibodies Immunoglobulins Antibodies, Monoclonal Prednisolone hemisuccinate Prednisolone phosphate |