Brentuximab Vedotin With or Without Nivolumab in Treating Patients With Relapsed or Refractory CD30+ Lymphoma
Primary Purpose
Recurrent Hodgkin Lymphoma, Recurrent Non-Hodgkin Lymphoma, Refractory Hodgkin Lymphoma
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Brentuximab Vedotin
Laboratory Biomarker Analysis
Nivolumab
Sponsored by
About this trial
This is an interventional treatment trial for Recurrent Hodgkin Lymphoma
Eligibility Criteria
Inclusion Criteria:
- Relapsed or refractory CD30+ lymphoma that has either achieved < PR to brentuximab vedotin (minimum of 2 cycles), progressed while receiving brentuximab vedotin, or progressed within 6 months of the last dose of brentuximab vedotin
- Documented expression of CD30 on tumor cells
- Absolute neutrophil count (ANC) > 1,000/uL
- Platelets > 50,000/uL
- Serum creatinine < 1.5 mg/dL OR creatinine clearance > 60 mL/min
- Bilirubin < 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN
- Measurable disease by computed tomography (CT) or similar (e.g. magnetic resonance imaging [MRI]) criteria (> 1.5 cm)
- Age >= 18 yrs at the time of the first dose of study drug
- Resolution of all non-hematologic brentuximab vedotin-related and nivolumab-related adverse events (AEs) to < Grade 2
- All patients must be informed of the investigational nature of this study and have given written consent in accordance with institutional and federal guidelines
- Patients must be anticipated to complete at least 2 cycles of chemotherapy on study
- Expected survival if untreated of > 90 days
Exclusion Criteria:
- Prior transplant within 100 days
- Radioimmunotherapy within 12 weeks
- Known human immunodeficiency virus (HIV) or hepatitis B positivity or prior progressive multifocal leukoencephalopathy (PML)
- Active infection or other medical condition which would preclude treatment in the opinion of the principal investigator; this would include a corrected diffusing capacity of the lungs for carbon monoxide (DLCO) of < 60% predicted or symptomatic interstitial lung disease
- Eastern Cooperative Oncology Group (ECOG) performance status > 2
- Known active central nervous system (CNS) involvement
- Peripheral neuropathy > grade 1 if due to brentuximab vedotin or any peripheral neuropathy > grade 2
- Intolerance to brentuximab vedotin
- Concurrent use of other anti-cancer agents or experimental treatments
- No current or prior autoimmune disease with the exception of vitiligo and autoimmune alopecia (Arm B only)
- Pregnancy or breastfeeding; (females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin [beta-hCG] pregnancy test result within 7 days prior to the first dose of brentuximab vedotin; females with false positive results and documented verification that the patient is not pregnant are eligible for participation; females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy; females of childbearing potential and males who have partners of childbearing potential must agree to use 2 effective contraceptive methods during the study and for 6 months following the last dose of brentuximab vedotin or 6 months following the last dose of nivolumab, whichever is later)
Sites / Locations
- Fred Hutch/University of Washington Cancer ConsortiumRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm A (brentuximab vedotin)
Arm B (brentuximab vedotin, nivolumab)
Arm Description
Patients receive brentuximab vedotin IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Outcomes
Primary Outcome Measures
Overall response rate as measured by the Cheson 2007 criteria
No formal statistical measures will be pre-specified. This protocol will be deemed a "success" if the absolute response rate in this group of patients is >= 20%.
Secondary Outcome Measures
Full Information
NCT ID
NCT01703949
First Posted
October 8, 2012
Last Updated
April 28, 2023
Sponsor
University of Washington
1. Study Identification
Unique Protocol Identification Number
NCT01703949
Brief Title
Brentuximab Vedotin With or Without Nivolumab in Treating Patients With Relapsed or Refractory CD30+ Lymphoma
Official Title
A Pilot Study of Weekly Brentuximab Vedotin or Brentuximab Vedotin Plus Nivolumab Every 3 Weeks in Patients With CD30+ Malignancies Refractory to Every ≥ 3 Week Brentuximab Vedotin
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 20, 2013 (Actual)
Primary Completion Date
September 1, 2024 (Anticipated)
Study Completion Date
September 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Washington
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This phase II pilot trial studies how well brentuximab vedotin with or without nivolumab works in treating patients with CD30+ lymphoma that has come back after a period of improvement or does not respond to treatment. Biological therapies, such as brentuximab vedotin, may stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as nivolumab may interfere with the ability of tumor cells to grow and spread. Giving brentuximab vedotin with or without nivolumab may work better in treating patients with CD30+ lymphoma.
Detailed Description
OUTLINE:
ARM A (CLOSED TO ACCRUAL): Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 3-5 weeks, every 3 months for 1 year, and then every 6 months for 4 years.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Hodgkin Lymphoma, Recurrent Non-Hodgkin Lymphoma, Refractory Hodgkin Lymphoma, Refractory Non-Hodgkin Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm A (brentuximab vedotin)
Arm Type
Experimental
Arm Description
Patients receive brentuximab vedotin IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Arm Title
Arm B (brentuximab vedotin, nivolumab)
Arm Type
Experimental
Arm Description
Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Brentuximab Vedotin
Other Intervention Name(s)
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
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Biological
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo, CMAB819, Nivolumab Biosimilar CMAB819
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Overall response rate as measured by the Cheson 2007 criteria
Description
No formal statistical measures will be pre-specified. This protocol will be deemed a "success" if the absolute response rate in this group of patients is >= 20%.
Time Frame
Up to 5 weeks after completion of study treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Relapsed or refractory CD30+ lymphoma that has either achieved < PR to brentuximab vedotin (minimum of 2 cycles), progressed while receiving brentuximab vedotin, or progressed within 6 months of the last dose of brentuximab vedotin
Documented expression of CD30 on tumor cells
Absolute neutrophil count (ANC) > 1,000/uL
Platelets > 50,000/uL
Serum creatinine < 1.5 mg/dL OR creatinine clearance > 60 mL/min
Bilirubin < 1.5 x upper limit of normal (ULN)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN
Measurable disease by computed tomography (CT) or similar (e.g. magnetic resonance imaging [MRI]) criteria (> 1.5 cm). (Patients with cutaneous lymphoma only require measurable disease by Olsen Criteria)
Age >= 18 yrs at the time of the first dose of study drug
Resolution of all non-hematologic brentuximab vedotin-related and nivolumab-related adverse events (AEs) to < Grade 2
All patients must be informed of the investigational nature of this study and have given written consent in accordance with institutional and federal guidelines
Patients must be anticipated to complete at least 2 cycles of chemotherapy on study
Expected survival if untreated of > 90 days
Exclusion Criteria:
Prior transplant within 100 days
Radioimmunotherapy within 12 weeks
Known human immunodeficiency virus (HIV) or hepatitis B positivity or prior progressive multifocal leukoencephalopathy (PML)
Active infection or other medical condition which would preclude treatment in the opinion of the principal investigator; this would include a corrected diffusing capacity of the lungs for carbon monoxide (DLCO) of < 60% predicted or symptomatic interstitial lung disease
Eastern Cooperative Oncology Group (ECOG) performance status > 2
Known active central nervous system (CNS) involvement
Peripheral neuropathy > grade 1 if due to brentuximab vedotin or any peripheral neuropathy > grade 2
Intolerance to brentuximab vedotin
Concurrent use of other anti-cancer agents or experimental treatments
No current or prior autoimmune disease with the exception of vitiligo and autoimmune alopecia (Arm B only)
Pregnancy or breastfeeding; (females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin [beta-hCG] pregnancy test result within 7 days prior to the first dose of brentuximab vedotin; females with false positive results and documented verification that the patient is not pregnant are eligible for participation; females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy; females of childbearing potential and males who have partners of childbearing potential must agree to use 2 effective contraceptive methods during the study and for 6 months following the last dose of brentuximab vedotin or 6 months following the last dose of nivolumab, whichever is later)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ajay K. Gopal
Phone
206-606-2037
Email
agopal@uw.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ajay K. Gopal
Organizational Affiliation
Fred Hutch/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutch/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ajay K. Gopal
Phone
206-606-2037
Email
agopal@uw.edu
First Name & Middle Initial & Last Name & Degree
Ajay K. Gopal
12. IPD Sharing Statement
Learn more about this trial
Brentuximab Vedotin With or Without Nivolumab in Treating Patients With Relapsed or Refractory CD30+ Lymphoma
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