Pembrolizumab and Brentuximab Vedotin vs GDP and Stem Cell Transplant for Relapsed/Refractory Hodgkin Lymphoma
Primary Purpose
Hodgkin Lymphoma
Status
Recruiting
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Gemcitabine
Dexamethasone
Cisplatin
Brentuximab vedotin
Pembrolizumab
Sponsored by
About this trial
This is an interventional treatment trial for Hodgkin Lymphoma
Eligibility Criteria
Inclusion Criteria:
- History of classic Hodgkin lymphoma by histopathology and now have relapsed or refractory disease after anthracycline-containing chemotherapy and eligible for high dose chemotherapy and autologous stem cell transplant
- 18 years of age or greater
- ECOG performance status 0-1
- Clinically and/or radiologically measurable disease as per the Lugano 2014 classification
- Life expectancy > 90 days
- Absolute neutrophils ≥1.0 x 10^9/L; Platelets ≥75 x 10^9/L; Hemoglobin ≥80 g/L: Bilirubin ≤1.50 x UNL; AST and ALT ≤2.50 x UNL; Serum creatinine <1.55 x UNL or Creatinine clearance ≥30 mL/min
- Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires and/or health utility in either English or French
- Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.
- Patient must be accessible for treatment and follow-up. Patients enrolled on this trial must be treated and followed at the participating centre.
- In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient enrollment
- Women/men of childbearing potential must have agreed to use a highly effective contraceptive method during the study plus approximately 6 months after treatment completion
- All patients must have a tumour block from their primary diagnostic biopsy available and the centre/pathologist must have agreed to release the block or recently cut slides for correlative analysis if the patient has consented.
Exclusion Criteria:
- Patients who have received prior salvage systemic therapy for their relapsed or refractory disease.
- History of peripheral neuropathy or dyspnea ≥ grade 2
- Patients with a history of other malignancies except: adequately treated non-melanoma skin cancer and superficial bladder cancer, curatively treated in-situ cancer of the cervix or breast, or localized excised prostate cancer, other solid tumours curatively treated with no evidence of disease for > 3 years
- History of active CNS disease
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (at doses more than 10 mg prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first and any dose of trial treatment
- Has active autoimmune disease that has required systemic treatment in the past 3 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs) or history of allogeneic transplantation. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Known history of human immunodeficiency virus (HIV), active Hepatitis C Virus infection, active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics. Patients that are Hepatitis B core antibody positive are eligible if they are HBV DNA negative and are concurrently treated with anti-viral therapy. Patients with a past history of hepatitis C who have eradicated the virus are eligible
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, angina, or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
- Documented history of cerebral vascular event (stroke or transient ischemic attack)
- History of progressive multifocal leukoencephalopathy (PML).
- Any serious active disease or co-morbid medical condition, including psychiatric illness, judged by the local investigator to preclude safe administration of the planned protocol treatment or required follow-up
- Any other serious intercurrent illness, life threatening condition, organ system dysfunction, or medical condition judged by the local investigator to compromise the subject's safety (for example): active, uncontrolled bacterial, fungal or viral infection; clinically significant cardiac dysfunction or cardiovascular disease
- Patients who have been vaccinated with live, attenuated vaccines within 4 weeks of enrollment
- Pregnant or lactating females, or women/men of childbearing potential not willing to use an adequate method of birth control for the duration of the study through 6 months after the last dose of trial treatment
- Patients are not eligible if they have had a prior infusion reaction to the study drugs or their components > grade 2
- Patient has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
- Patient has had an allogenic tissue/solid organ transplant
- Concurrent or within the previous 4 weeks, treatment with other investigational drugs or anti-cancer therapy
- Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A one-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy)
Sites / Locations
- Tom Baker Cancer CentreRecruiting
- BCCA - Vancouver Cancer CentreRecruiting
- QEII Health Sciences CentreRecruiting
- Juravinski Cancer Centre at Hamilton Health SciencesRecruiting
- London Regional Cancer ProgramRecruiting
- Ottawa Hospital Research InstituteRecruiting
- University Health NetworkRecruiting
- The Jewish General HospitalRecruiting
- The Research Institute of the McGill UniversityRecruiting
- CIUSSS de l'Estrie - Centre hospitalierRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
GDP
Brentuximab vedotin + Pembrolizumab
Arm Description
Outcomes
Primary Outcome Measures
Complete response rate by PET Deauville criteria (score 1-3) of pembrolizumab and brentuximab vedotin compared to standard GDP (gemcitabine, dexamethasone, cisplatin) given as salvage therapy
Secondary Outcome Measures
Progression-free survival
Event-free survival
Overall survival
Successful stem cell collection rate
Transplantation rate
Number and severity of adverse events
Participant-reported Quality of Life utilizing EORTC QLQ-C30
Participant-reported toxicity utilizing PRO-CTCAE
Participant-reported Quality of Life utilizing FACT-LYM evaluating symptoms and concerns associated specifically with the lymphoma disease and/or disease treatment.
Participant-reported Quality of Life utilizing FACT/GOG-Ntx-Subscale specifically with chemotherapy-induced neuropathy
Health Economics utilizing EQ-5D-5L
Health Economics financial toxicity utilizing FACIT-COST
Full Information
NCT ID
NCT05180097
First Posted
December 17, 2021
Last Updated
September 11, 2023
Sponsor
Canadian Cancer Trials Group
Collaborators
Merck Sharp & Dohme LLC, Seagen Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05180097
Brief Title
Pembrolizumab and Brentuximab Vedotin vs GDP and Stem Cell Transplant for Relapsed/Refractory Hodgkin Lymphoma
Official Title
A Randomized Phase II Study of Pembrolizumab and Brentuximab Vedotin Versus GDP, Followed by High Dose Chemotherapy and Autologous Stem Cell Transplantation for Relapsed/Refractory Classical Hodgkin Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 1, 2022 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Canadian Cancer Trials Group
Collaborators
Merck Sharp & Dohme LLC, Seagen Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is being done to determine if two new drugs can shrink or eliminate classical Hodgkins lymphoma.
Detailed Description
Treatment given to participants whose disease has not responded to (refractory) or returned (relapsed) after previous treatment is known as salvage treatment.
The standard of care for participants who are not in a study is salvage treatment with gemcitabine, dexamethasone and cisplatin (GDP). This treatment can reduce symptoms and may stop the lymphoma from growing for a few months or longer. This standard treatment is approved by Health Canada
We are doing this study because we want to find out if treatment with Pembrolizumab and Brentuximab vedotin is better or worse than the standard of care for this type of cancer, classical Hodgkin lymphoma. The standard of care is defined as care most people get for your cancer.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hodgkin Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
84 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
GDP
Arm Type
Active Comparator
Arm Title
Brentuximab vedotin + Pembrolizumab
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
1000mg/m2 IV, 30 mins D1, D8
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
40mg daily PO, D1-D4
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
75mg/m2 IV, 1 hour, D1
Intervention Type
Drug
Intervention Name(s)
Brentuximab vedotin
Intervention Description
1.8 mg/kg IV, 30 mins, Q21 days
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Intervention Description
200mg IV, 30 mins, Q 21 days
Primary Outcome Measure Information:
Title
Complete response rate by PET Deauville criteria (score 1-3) of pembrolizumab and brentuximab vedotin compared to standard GDP (gemcitabine, dexamethasone, cisplatin) given as salvage therapy
Time Frame
52 months
Secondary Outcome Measure Information:
Title
Progression-free survival
Time Frame
52 months
Title
Event-free survival
Time Frame
52 months
Title
Overall survival
Time Frame
52 months
Title
Successful stem cell collection rate
Time Frame
52 months
Title
Transplantation rate
Time Frame
52 months
Title
Number and severity of adverse events
Time Frame
52 months
Title
Participant-reported Quality of Life utilizing EORTC QLQ-C30
Time Frame
52 months
Title
Participant-reported toxicity utilizing PRO-CTCAE
Time Frame
52 months
Title
Participant-reported Quality of Life utilizing FACT-LYM evaluating symptoms and concerns associated specifically with the lymphoma disease and/or disease treatment.
Time Frame
52 months
Title
Participant-reported Quality of Life utilizing FACT/GOG-Ntx-Subscale specifically with chemotherapy-induced neuropathy
Time Frame
52 months
Title
Health Economics utilizing EQ-5D-5L
Time Frame
52 months
Title
Health Economics financial toxicity utilizing FACIT-COST
Time Frame
52 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
History of classic Hodgkin lymphoma by histopathology and now have relapsed or refractory disease after anthracycline-containing chemotherapy and eligible for high dose chemotherapy and autologous stem cell transplant
18 years of age or greater
ECOG performance status 0-1
Clinically and/or radiologically measurable disease as per the Lugano 2014 classification
Life expectancy > 90 days
Absolute neutrophils ≥1.0 x 10^9/L; Platelets ≥75 x 10^9/L; Hemoglobin ≥80 g/L: Bilirubin ≤1.50 x UNL; AST and ALT ≤2.50 x UNL; Serum creatinine <1.55 x UNL or Creatinine clearance ≥30 mL/min
Participant is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires and/or health utility in either English or French
Participant consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each participant must sign a consent form prior to enrollment in the trial to document their willingness to participate.
Participants must be accessible for treatment and follow-up.
In accordance with CCTG policy, protocol treatment is to begin within 2 working days of participant enrollment
Women/men of childbearing potential must have agreed to use a highly effective contraceptive method during the study plus approximately 6 months after treatment completion
All patients must have a tumour block from their primary diagnostic biopsy and relapse/refractory biopsy if available and the centre/pathologist must have agreed to release the block or recently cut slides for correlative analysis if the participant has consented. If the primary diagnostic biopsy is not accessible, the original pathology report should be submitted for review and a biopsy from the relapse/refractory disease must be submitted.
Exclusion Criteria:
Participants who have received prior salvage systemic therapy for their relapsed or refractory disease.
History of peripheral neuropathy or dyspnea ≥ grade 2
Participants with a history of other malignancies except: adequately treated non-melanoma skin cancer and superficial bladder cancer, curatively treated in-situ cancer of the cervix or breast, or localized excised prostate cancer, other solid tumours curatively treated with no evidence of disease for > 3 years
History of active CNS disease
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (at doses more than 10 mg prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first and any dose of trial treatment
Has active autoimmune disease that has required systemic treatment in the past 3 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs) or history of allogeneic transplantation. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
Known history of human immunodeficiency virus (HIV), active Hepatitis C Virus infection, active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics. Participants that are Hepatitis B core antibody positive are eligible if they are HBV DNA negative and are concurrently treated with anti-viral therapy. Participants with a past history of hepatitis C who have eradicated the virus are eligible
Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, angina, or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
Documented history of cerebral vascular event (stroke or transient ischemic attack)
History of progressive multifocal leukoencephalopathy (PML).
Any serious active disease or co-morbid medical condition, including psychiatric illness, judged by the local investigator to preclude safe administration of the planned protocol treatment or required follow-up
Any other serious intercurrent illness, life-threatening condition, organ system dysfunction, or medical condition judged by the local investigator to compromise the subject's safety (for example): active, uncontrolled bacterial, fungal or viral infection; clinically significant cardiac dysfunction or cardiovascular disease
Participants who have been vaccinated with live, attenuated vaccines within 4 weeks of enrollment
Pregnant or lactating females, or women/men of childbearing potential not willing to use an adequate method of birth control for the duration of the study through 6 months after the last dose of trial treatment
Participants are not eligible if they have had a prior infusion reaction to the study drugs or their components > grade 2
Participant has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
Participant has had an allogenic tissue/solid organ transplant
Concurrent or within the previous 4 weeks of randomization, treatment with other investigational drugs or anti-cancer therapy
Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A one-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Annette Hay
Phone
613-533-6430
Email
ahay@ctg.queensu.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Lois Shepherd
Phone
613-533-6430
Email
lshepherd@ctg.queensu.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kerry Savage
Organizational Affiliation
BCCA-Vancouver Cancer Centre
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
John Kuruvilla
Organizational Affiliation
University Health Network, Princess Margaret Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Tom Baker Cancer Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sarah Perry
Phone
403 521-3347
Facility Name
BCCA - Vancouver Cancer Centre
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kerry J. Savage
Phone
604 877-6000
Ext
2641
Facility Name
QEII Health Sciences Centre
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 1V7
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mary-Margaret Keating
Phone
902 473-7006
Facility Name
Juravinski Cancer Centre at Hamilton Health Sciences
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amaris Balitsky
Phone
905 387-9495
Facility Name
London Regional Cancer Program
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5W9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joy Elise Mangel
Phone
519 685-8500
Ext
52391
Facility Name
Ottawa Hospital Research Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Isabelle Bence-Bruckler
Phone
613 737-8152
Facility Name
University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Kuruvilla
Phone
416 946-2827
Facility Name
The Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nathalie Johnson
Phone
514 398-8307
Facility Name
The Research Institute of the McGill University
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kelly Davison
Phone
514 934-1934
Ext
31558
Facility Name
CIUSSS de l'Estrie - Centre hospitalier
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1H 5N4
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stephanie Desilets
Phone
819 346-1110
Ext
74816
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Pembrolizumab and Brentuximab Vedotin vs GDP and Stem Cell Transplant for Relapsed/Refractory Hodgkin Lymphoma
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