Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma

• Sponsor: Seagen Inc. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03646123
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 255
• Locations: 76
• Arms: 3
• Anticipated Duration (Months): 88.3
• Patients Per Site: 3.4
• Patients Per Site Per Month: 0

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
Hodgkin Lymphoma	Drug: brentuximab vedotin; Drug: doxorubicin; Drug: vinblastine; Drug: dacarbazine; Drug: G-CSF; Drug: nivolumab	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

• Study Type: Interventional
• Actual Enrollment: 255 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Multiple Part Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma Subjects
• Actual Study Start Date: Jan 28, 2019
• Anticipated Primary Completion Date: Sep 30, 2022
• Anticipated Study Completion Date: Jun 7, 2026

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: Adcetris SGN-35 ; 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: filgrastim pegfilgrastim
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: Adcetris SGN-35 ; 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: Opdivo
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: Adcetris SGN-35 ; 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: Opdivo

Outcome Measures

Primary Outcome Measures

1. Febrile Neutropenia (FN) Rate (Part A) [Up to 6 months]

   Proportion of patients with treatment-emergent incidence of FN.

2. 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

1. Primary Refractory Disease Rate (Part A) [Up to 9 months]

   Proportion of participants with less than CR or relapse within 3 months of EOT.

2. CR Rate (Part A) [Up to 6 months]

   Proportion of patients with CR at EOT.

3. 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.

4. Subsequent Anticancer Therapy Utilization Rate (Part A) [Up to 2.5 years]

   Proportion of patients with subsequent anticancer therapies.

5. Mean Dose Intensity (Part A) [Up to 6 months]

6. 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.

7. Incidence of adverse events (Parts B and C) [Up to 7 months]

8. Incidence of laboratory abnormalities (Parts B and C) [Up to 7 months]

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

• Histologically confirmed cHL according to the current World Health Organization (WHO) Classification

• Bidimensional measurable disease as documented by PET/CT or CT imaging

• 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

• 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

• 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)

• Current therapy with other systemic anti-neoplastic or investigational agents

• Planned consolidative radiotherapy (Parts B and C only)

• 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)

• Grade 3 or higher pulmonary disease unrelated to underlying malignancy

• Documented history of idiopathic interstitial pneumonia or diffusing capacity of the lung for carbon monoxide <50% predicted

• History of a cerebral vascular event within 6 months of first dose of study drug

• 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

• 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.

• Responsible Party: Seagen Inc.
• ClinicalTrials.gov Identifier: NCT03646123
• Other Study ID Numbers: SGN35-027
• First Posted: Aug 24, 2018
• Last Update Posted: Jun 30, 2022
• Last Verified: Jun 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Seagen Inc.: Brentuximab vedotin; Doxorubicin; Vinblastine; Dacarbazine; Nivolumab; Seattle Genetics
• Additional relevant MeSH terms: Lymphoma; Hodgkin Disease; Doxorubicin; Nivolumab; Dacarbazine; Brentuximab Vedotin; Vinblastine

Study Results

No Results Posted as of Jun 30, 2022