Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma
Study Details
Study Description
Brief Summary
This trial will study two treatment combinations for classical Hodgkin lymphoma (cHL). This trial will find out if these two treatment combinations work to treat cHL. It will also find out what side effects occur. A side effect is anything the drug does besides treating cancer. This study will have three parts (Parts A, B, and C).
The drugs used in Part A are a combination of targeted anticancer drug (brentuximab vedotin) and three chemotherapy drugs (doxorubicin, vinblastine, and dacarbazine). These four drugs are called "A+AVD." Participants will be treated with granulocyte colony stimulating factor (G-CSF) following every dose of A+AVD for 6 cycles of treatment (12 doses).
Part A will look at whether the A+AVD drug combination reduces the number of participants who experience the side effect of febrile neutropenia. Febrile neutropenia is a very low white blood cell count and a fever, which can be life threatening.
Parts B and C will use drug combination of brentuximab vedotin, plus nivolumab, doxorubicin, and dacarbazine. These four drugs are called "AN+AD." Parts B and C will study how well the drugs work to treat cHL and what side effects they cause.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
This study will have three parts.
Part A of the study is designed to evaluate the incidence of febrile neutropenia, efficacy, and dose intensity in participants with advanced stage classical Hodgkin lymphoma (cHL) receiving granulocyte colony stimulating factor primary prophylaxis (G-PP) administration during treatment with frontline A+AVD. In Part A, participants will be treated with granulocyte colony stimulating factor (G-CSF) following every dose of A+AVD for 6 cycles of treatment. Participants will be treated using institutional standard of care practices for the majority of treatment decisions.
Part B is designed to evaluate the combination of brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine (AN+AD) as frontline treatment in participants with advanced cHL. In Part B, participants will be given AN+AD combination for 6 cycles of treatment. This part of the trial will look at whether this combination of drugs is effective and tolerable in participants with Stage II with bulky mediastinal disease and Stage III or IV cHL.
Part C is designed to evaluate AN+AD as frontline treatment in participants with early stage cHL. In Part C, participants will be given AN+AD combination for 4 cycles of treatment. This part of the trial will look at whether this combination of drugs is effective and tolerable in participants with Stage I or II cHL with non-bulky mediastinal disease.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Part A: A+AVD Brentuximab vedotin (A) plus doxorubicin (+A), vinblastine (V), and dacarbazine (D) administered by intravenous (IV) infusion in participants with advanced stage classical Hodgkin lymphoma (cHL) during each treatment cycle. |
Drug: brentuximab vedotin
1.2 mg/kg by IV infusion
Other Names:
Drug: doxorubicin
25 mg/m^2 by IV infusion
Drug: vinblastine
6 mg/m^2 by IV infusion
Drug: dacarbazine
375 mg/m^2 by IV infusion
Drug: G-CSF
Granulocyte colony stimulating factor (G-CSF) primary prophylaxis administered 24-36 hours after each dose of A+AVD
Other Names:
|
Experimental: Part B: AN+AD Brentuximab vedotin (A) plus nivolumab (N), doxorubicin (+A), and dacarbazine (D) administered separately by IV infusion in participants with Stage II bulky mediastinal disease and Stage III or IV cHL during each treatment cycle. |
Drug: brentuximab vedotin
1.2 mg/kg by IV infusion
Other Names:
Drug: doxorubicin
25 mg/m^2 by IV infusion
Drug: dacarbazine
375 mg/m^2 by IV infusion
Drug: nivolumab
240 mg by IV infusion
Other Names:
|
Experimental: Part C: AN+AD Brentuximab vedotin (A) plus nivolumab (N), doxorubicin (+A), and dacarbazine (D) administered separately by IV infusion in participants with Stage I or II cHL with non-bulky mediastinal disease during each treatment cycle. |
Drug: brentuximab vedotin
1.2 mg/kg by IV infusion
Other Names:
Drug: doxorubicin
25 mg/m^2 by IV infusion
Drug: dacarbazine
375 mg/m^2 by IV infusion
Drug: nivolumab
240 mg by IV infusion
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Febrile Neutropenia (FN) Rate (Part A) [Up to 6 months]
Proportion of patients with treatment-emergent incidence of FN.
- Complete response (CR) rate (Parts B and C) [Up to 6 months]
Proportion of participants with CR at end of treatment (EOT), according to the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC).
Secondary Outcome Measures
- Primary Refractory Disease Rate (Part A) [Up to 9 months]
Proportion of participants with less than CR or relapse within 3 months of EOT.
- CR Rate (Part A) [Up to 6 months]
Proportion of patients with CR at EOT.
- Physician-reported Progression Free Survival (PFS) (Part A) [Up to 2 years]
The physician-reporting PFS is defined as the time from start of study treatment to first documentation of progression per investigator or to death due to any cause, whichever comes first.
- Subsequent Anticancer Therapy Utilization Rate (Part A) [Up to 2.5 years]
Proportion of patients with subsequent anticancer therapies.
- Mean Dose Intensity (Part A) [Up to 6 months]
- Rate of Dose Reduction and Delays (Part A) [Up to 6 months]
Proportion of patients with dose reductions or delays related to any component of A+AVD.
- Incidence of adverse events (Parts B and C) [Up to 7 months]
- Incidence of laboratory abnormalities (Parts B and C) [Up to 7 months]
- Overall response rate (ORR) at EOT (Parts B and C) [Up to 6 months]
ORR is defined as the proportion of participants with CR or partial response (PR) at EOT.
- Duration of response (DOR) (Parts B and C) [Up to 5 years]
DOR is defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression per LYRIC or death, whichever comes first.
- Duration of complete response (DOCR) (Parts B and C) [Up to 5 years]
DOCR is defined as the time from the first documentation of complete tumor response (CR) to the first documentation of tumor progression per LYRIC or death, whichever comes first. DOCR will only be calculated for the subgroup of subjects achieving CR.
- Event-free survival (EFS) (Parts B and C) [Up to 5 years]
EFS is defined as the time from start of study treatment to the first documentation of objective tumor progression, death due to any cause, or receipt of subsequent anticancer therapy to treat residual or progressive disease, whichever comes first.
- PFS (Parts B and C) [Up to 5 years]
PFS is defined as the time from start of study treatment to first documentation of objective tumor progression or death.
- Overall survival (OS) (Parts B and C) [Up to 5 years]
Overall survival is defined as the time from start of study treatment to the date of death due to any cause.
Eligibility Criteria
Criteria
Inclusion Criteria
-
Treatment-naïve, classic Hodgkin lymphoma (cHL) participants
-
Participants enrolling in Part A of the study must have Ann Arbor Stage III or IV disease
-
Participants enrolling in Part B of the study must have Ann Arbor Stage I or II cH: with bulky mediastinal disease, or Stage III or IV
-
Participants enrolling in Part C of the study must have Ann Arbor Stage I or II cHL without bulky disease
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Histologically confirmed cHL according to the current World Health Organization (WHO) Classification
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Bidimensional measurable disease as documented by PET/CT or CT imaging
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Age 12 years or older in the United States. For regions outside of the US, participants must 18 years or older.
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Exclusion Criteria
-
Nodular lymphocyte predominant HL
-
History of another malignancy within 3 years of the first dose of study drug or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk or metastasis or death. Participants with nonmelanoma skin cancer, localized prostate cancer, or carcinoma in situ of any type are not excluded if they have undergone complete resection
-
Prior immunosuppressive chemotherapy, therapeutic radiation, or any immunotherapy within 4 weeks of the first study drug dose
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Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
-
Active cerebral/meningeal disease related to the underlying malignancy
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Any active Grade 3 or higher viral, bacterial, or fungal infection within two weeks of the first dose of study drug (Grade 3 defined by the National Cancer Institute's Common Terminology Criteria for Adverse Events, NCI CTCAE Version 4.03)
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Current therapy with other systemic anti-neoplastic or investigational agents
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Planned consolidative radiotherapy (Parts B and C only)
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Active interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity (Parts B and C only)
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Grade 3 or higher pulmonary disease unrelated to underlying malignancy
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Documented history of idiopathic interstitial pneumonia or diffusing capacity of the lung for carbon monoxide <50% predicted
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History of a cerebral vascular event within 6 months of first dose of study drug
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Child-Pugh B or C hepatic impairment
-
Grade 2 or higher peripheral sensory or motor neuropathy
-
Participants with acute or chronic graft-versus-host-disease (GvHD) or receiving immunosuppressive therapy as treatment or as prophylaxis against GvHD
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Previous treatment with brentuximab vedotin
-
Participants who are pregnant or breastfeeding
-
Other serious condition that would impair the participant's ability to receive or tolerate the planned treatment and follow-up
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Compassionate Care Research Group | Fountain Valley | California | United States | 92708 |
2 | Rocky Mountain Cancer Centers - Aurora | Aurora | Colorado | United States | 80012 |
3 | University of Colorado Health Memorial Hospital | Colorado Springs | Colorado | United States | 80909 |
4 | Cancer Centers of Colorado - Denver | Denver | Colorado | United States | 80218 |
5 | Poudre Valley Health System (PVHS) | Fort Collins | Colorado | United States | 80528 |
6 | SCL Health - St. Mary's Hospital & Medical Center | Grand Junction | Colorado | United States | 81501 |
7 | Miami Cancer Institute at Baptist Health, Inc. | Miami | Florida | United States | 33176 |
8 | Florida Cancer Specialists - North Region | Saint Petersburg | Florida | United States | 33705 |
9 | Cardinal Bernardin Cancer Center / Loyola University Medical Center | Maywood | Illinois | United States | 60153 |
10 | Illinois Cancer Specialists / Advocate Lutheran General Hospital | Niles | Illinois | United States | 60714 |
11 | Illinois Cancer Care | Peoria | Illinois | United States | 61615 |
12 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
13 | Beth Israel Deaconess Medical Center | Boston | Massachusetts | United States | 02215 |
14 | Karmanos Cancer Institute / Wayne State University | Detroit | Michigan | United States | 48201 |
15 | Henry Ford Health System | Detroit | Michigan | United States | 48202 |
16 | Minnesota Oncology Hematology P.A. | Edina | Minnesota | United States | 55435 |
17 | Washington University in St Louis | Saint Louis | Missouri | United States | 63110 |
18 | New Jersey Hematology Oncology Associates, LLC | Brick | New Jersey | United States | 08724 |
19 | Regional Cancer Care Associates - Freehold | Freehold | New Jersey | United States | 07728 |
20 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
21 | Regional Cancer Care Associates - Howell | Howell | New Jersey | United States | 07731 |
22 | Morristown Medical Center/ Carol G. Simon Cancer Center | Morristown | New Jersey | United States | 07960 |
23 | Regional Cancer Care Associates - Mount Holly | Mount Holly | New Jersey | United States | 08060 |
24 | Regional Cancer Care Associates - Central Jersey | Somerville | New Jersey | United States | 08876 |
25 | Regional Cancer Care Associates - Sparta | Sparta | New Jersey | United States | 07871 |
26 | New York Oncology Hematology, P.C. | Albany | New York | United States | 12208 |
27 | CareMount Medical Group | Mount Kisco | New York | United States | 10549-3412 |
28 | Mount Sinai Medical Center | New York | New York | United States | 10029 |
29 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
30 | Clinical Research Alliance - Abraham Mittelman, MD, LLC | Purchase | New York | United States | 10577 |
31 | Clinical Research Alliance - Morton Coleman, MD | Westbury | New York | United States | 11590 |
32 | Wake Forest Baptist Medical Center / Wake Forest University | Winston-Salem | North Carolina | United States | 27157 |
33 | Oncology Hematology Care | Cincinnati | Ohio | United States | 45242 |
34 | Case Western Reserve University / University Hospitals Cleveland Medical Center | Cleveland | Ohio | United States | 44106 |
35 | Cleveland Clinic, The | Cleveland | Ohio | United States | 44195 |
36 | Toledo Clinic Cancer Center | Toledo | Ohio | United States | 43623 |
37 | Willamette Valley Cancer Institute and Research Center | Eugene | Oregon | United States | 97401 |
38 | Providence Portland Medical Center | Portland | Oregon | United States | 97213 |
39 | Medical University of South Carolina/Hollings Cancer Center | Charleston | South Carolina | United States | 29425 |
40 | University of Tennessee | Knoxville | Tennessee | United States | 37920 |
41 | Tennessee Oncology - Nashville | Nashville | Tennessee | United States | 37203 |
42 | Texas Oncology - Austin Midtown | Austin | Texas | United States | 78705 |
43 | Texas Oncology - Medical City Dallas | Dallas | Texas | United States | 75230 |
44 | Texas Oncology - Flower Mound | Flower Mound | Texas | United States | 75028 |
45 | Brooke Army Medical Center | Fort Sam Houston | Texas | United States | 78234 |
46 | Texas Oncology - Fort Worth 12th Avenue | Fort Worth | Texas | United States | 76104 |
47 | MD Anderson Cancer Center / University of Texas | Houston | Texas | United States | 77030-4095 |
48 | Texas Oncology - San Antonio Medical Center | San Antonio | Texas | United States | 78240 |
49 | Texas Oncology - Tyler | Tyler | Texas | United States | 75702 |
50 | Huntsman Cancer Institute/University of Utah | Salt Lake City | Utah | United States | 84112 |
51 | Virginia Cancer Specialists, PC | Fairfax | Virginia | United States | 22031 |
52 | Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care | Salem | Virginia | United States | 24153 |
53 | Kadlec Clinic Hematology and Oncology | Kennewick | Washington | United States | 99336 |
54 | Vista Oncology Inc PS | Olympia | Washington | United States | 98506 |
55 | Seattle Cancer Care Alliance / University of Washington | Seattle | Washington | United States | 98109-1023 |
56 | Royal Adelaide Hospital | Adelaide | Other | Australia | 5000 |
57 | Ballarat Regional Integrated Cancer Care | Ballarat | Other | Australia | 3350 |
58 | Monash Medical Centre | Clayton | Other | Australia | 3168 |
59 | Epworth Healthcare | Victoria | Other | Australia | 3002 |
60 | Fakultni nemocnice Hradec Kralove-oddeleni klinicke hematologie | Hradec Kralove | Other | Czechia | 500 05 |
61 | Fakultni Nemocnice Kralovske Vinohrady | Praha 10 | Other | Czechia | 100 34 |
62 | Azienda Ospedaliera Spedali Civili di Brescia | Brescia | Other | Italy | 25123 |
63 | IRCSS Policlinico San Matteo | Pavia | Other | Italy | 27100 |
64 | Azienda Ospedaliera Universitaria Senese | Siena | Other | Italy | 53100 |
65 | Azienda Ospedaliera Citta della Salute e della Scienza di Torino | Torino | Other | Italy | 10126 |
66 | Pratia MCM Krakow | Krakow | Other | Poland | 30-510 |
67 | Hospital del Mar | Barcelona | Other | Spain | 08003 |
68 | Hospital Universitario Vall d'Hebron | Barcelona | Other | Spain | 08035 |
69 | Institut Catala d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet) | Barcelona | Other | Spain | 08908 |
70 | Hospital Universitario de Girona Doctor Josep Trueta | Girona | Other | Spain | 17007 |
71 | Hospital Universitario Fundacion Jimenez Diaz | Madrid | Other | Spain | 28040 |
72 | Hospital Universitario 12 de Octubre | Madrid | Other | Spain | 28041 |
73 | Hospital Puerta de Hierro Majadahonda | Majadahonda | Other | Spain | 28222 |
74 | Hospital Universitario Central de Asturias | Oviedo | Other | Spain | 33011 |
75 | Hospital Clinico Universitario de Salamanca | Salamanca | Other | Spain | 37007 |
76 | Hospital Universitari i Politecnic La Fe de Valencia | Valencia | Other | Spain | 46026 |
Sponsors and Collaborators
- Seagen Inc.
- Bristol-Myers Squibb
Investigators
- Study Director: Linda Ho, MD, Seagen Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SGN35-027