Doxorubicin, Vinblastine, Dacarbazine, Brentuximab Vedotin, and Nivolumab in Treating Patients With Stage I-II Hodgkin Lymphoma

NCT03233347 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: ACCRU-LY-1601NCI-2017-01308P30CA015083
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 9

Brief Summary

This phase II trial evaluates how well AVD (doxorubicin, vinblastine, dacarbazine) in combination with brentuximab vedotin and nivolumab work in treating patients with stage I-II Hodgkin lymphoma. Drugs used in the chemotherapy, such as doxorubicin, vinblastine, dacarbazine, and brentuximab vedotin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, and/or by stopping them from spreading. Targeted agent, such as nivolumab, may interfere with the ability of cancer cells to grow and spread by enhancing the immune system. Giving doxorubicin, vinblastine, dacarbazine, brentuximab vedotin, and nivolumab may improve survival of patients with stage I-II Hodgkin lymphoma.

Conditions

Ann Arbor Stage I Hodgkin Lymphoma; Ann Arbor Stage IA Hodgkin Lymphoma; Ann Arbor Stage IB Hodgkin Lymphoma; Ann Arbor Stage II Hodgkin Lymphoma; Ann Arbor Stage IIA Hodgkin Lymphoma; Ann Arbor Stage IIB Hodgkin Lymphoma; Classic Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  The distribution of progression-free survival time will be estimated using the method of Kaplan-Meier and the efficacy will be determined by the log rank statistic. Overall progression-free survival at 3 years will be reported.

  From registration, where progression is by computed tomography (CT)-based or positron emission tomography (PET)-CT based criteria, assessed at 3 years

Secondary Outcomes (11)

• Overall survival

  Time from registration to death due to any cause, assessed at 3 and 5 years

• The proportion of patients who are positron emission tomography (PET) negative

  After 3 courses (84 days)

• Proportion of patients who are positron emission tomography (PET) positive

  After 3 courses (84 days)

• Progression free survival

  From registration, where progression is by CT-based or PET-CT based criteria, assessed at 84 days

• Progression free survival

  From registration, where progression is by CT-based or PET-CT based criteria, assessed at 3 years

Study Arms (1)

Treatment (combination chemotherapy, nivolumab)

EXPERIMENTAL

Patients receive doxorubicin IV over 3-5 minutes, vinblastine IV over 3-5 minutes, and dacarbazine IV over \>= 30 minutes, and brentuximab vedotin IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients with PET-positive then receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30 minutes on day 1. Treatment repeats every 2 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. PET-positive patients then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 2 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. PET-negative patients receive nivolumab IV over 30 minutes on day 1 starting after AVD and BV treatment. Treatment repeats every 2 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Brentuximab Vedotin; Drug: Dacarbazine; Drug: Doxorubicin; Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Drug: Vinblastine

Interventions

Brentuximab Vedotin DRUG

Given IV

Also known as: ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35, Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35, cAC10-vcMMAE, SGN-35

Treatment (combination chemotherapy, nivolumab)

Dacarbazine DRUG

Given IV

Also known as: 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

Treatment (combination chemotherapy, nivolumab)

Doxorubicin DRUG

Given IV

Also known as: Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

Treatment (combination chemotherapy, nivolumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (combination chemotherapy, nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (combination chemotherapy, nivolumab)

Vinblastine DRUG

Given IV

Also known as: Vincaleucoblastine, VLB

Treatment (combination chemotherapy, nivolumab)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Measurable disease (\>= 1.5 cm) as assessed by 2 dimensional measurement by computed tomography (CT)
• Previously untreated stage I or II non-bulky (defined as a mass measuring \< 10 cm in the longest dimension by CT) classical Hodgkin lymphoma
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
• Life expectancy \>= 3 months
• Documented negative serologic testing for human immunodeficiency virus (HIV), hepatitis B (unless serologically positive due to prior vaccination), and hepatitis C =\< 1 year prior to registration
• White blood cell \>= 2,000 /mm\^3 without transfusion support \> 7 days prior to registration
• Hemoglobin \>= 8.5 g/dL without transfusion support \> 7 days prior to registration
• Absolute neutrophil count (ANC) \>= 1,000 cells/mm\^3 without transfusion support \> 7 days prior to registration
• Platelet count \>= 75,000/mm\^3 without transfusion support \> 7 days prior to registration
• Alanine and aspartate aminotransferase (ALT/AST) =\< 2.5 x upper limit of normal (ULN) obtained =\< 14 days prior to registration
• Total serum bilirubin =\< 1.5 x ULN (if documented Gilberts syndrome =\< 3 x ULN) obtained =\< 14 days prior to registration
• Serum creatinine =\< 1.5 x ULN or measured calculated creatinine clearance \>= 40 ml/min for subject with creatinine levels \> 1.5 x institutional ULN (per Cockcroft-Gault formula) obtained =\< 14 days prior to registration
• Negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 7 days prior to registration in women of child-bearing potential (WOCBP)
• Sexually active female of reproductive capability ie, WOCBP, has agreed to use a medically accepted form of contraception from time of registration to completion of study therapy through 24 weeks (6 months) after last dose of NVB or BV; Note: Females of non-child-bearing potential are those who are postmenopausal for \> 1 year or who have had a bilateral tubal ligation or hysterectomy
• Male subjects agree to use an adequate method of contraception starting with the first dose of study therapy through 31 weeks after the last dose of study therapy

You may not qualify if:

• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception
• Prior therapies including involved field radiation therapy
• Bulky disease (defined as a nodal mass measuring \>= 10 cm by CT)
• Known central nervous system (CNS) involvement
• Moderate or severe hepatic insufficiency Child-Pugh score \> 6
• Severe renal impairment (i.e. creatinine clearance \< 40 mL/min)
• Symptomatic cardiac disease including ventricular dysfunction, left ventricular ejection fraction \< 45%, symptomatic coronary artery disease or symptomatic arrhythmias
• Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy =\< 7 days prior to registration
• Known history of active TB (Bacillus tuberculosis)
• Requires therapy with agents that have a predisposition for hepatoxicity
• Hypersensitivity to NVB or any of its excipients or to any component of AVD + BV therapy
• Requires immunosuppressive doses of corticosteroid therapy (\> 10 mg/day prednisone equivalents) for \>= 2 weeks prior to registration

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (9)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203, United States

Location

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Washington Medical Center - Montlake

Seattle, Washington, 98195, United States

Location

MeSH Terms

Interventions

Brentuximab Vedotin; Dacarbazine; Doxorubicin; Nivolumab; Vinblastine

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Steven I Park

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2017
• First Posted: July 28, 2017
• Study Start: October 13, 2017
• Primary Completion: July 1, 2025
• Study Completion (Estimated): July 8, 2026
• Last Updated: October 3, 2025

Record last verified: 2025-09

Locations

US (9)