Study of Safety and Efficacy of Pembrolizumab and Chemotherapy in Participants With Newly Diagnosed Classical Hodgkin Lymphoma (cHL) (MK-3475-C11/KEYNOTE-C11) (KEYNOTE-C11)
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| ClinicalTrials.gov Identifier: NCT05008224 |
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Recruitment Status :
Active, not recruiting
First Posted : August 17, 2021
Last Update Posted : July 14, 2022
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Sponsor:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC
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Brief Summary:
The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) monotherapy, followed by chemotherapy, followed by pembrolizumab consolidation. The primary hypothesis of the study is that the complete response (CR) rate at the end of study intervention according to Lugano 2014 response criteria is higher than conventional chemotherapy.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Classical Hodgkin Lymphoma | Biological: Pembrolizumab Drug: Doxorubicin Drug: Vinblastine Drug: Dacarbazine Drug: Bleomycin Drug: Etoposide Drug: Cyclophosphamide Drug: Vincristine Drug: Procarbazine Drug: Prednisone | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 140 participants |
| Allocation: | N/A |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase 2 Study of Pembrolizumab and Chemotherapy in Patients With Newly Diagnosed Classical Hodgkin Lymphoma (KEYNOTE-C11) |
| Actual Study Start Date : | October 7, 2021 |
| Estimated Primary Completion Date : | July 19, 2023 |
| Estimated Study Completion Date : | June 15, 2026 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Pembrolizumab
| Arm | Intervention/treatment |
|---|---|
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Experimental: Pembrolizumab Monotherapy + Chemotherapy + Pembrolizumab Consolidation
Participants receive pembrolizumab monotherapy followed by chemotherapy with doxorubicin in combination with vinblastine & dacarbazine (AVD) or chemotherapy with escalated bleomycin in combination with etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, & prednisone (escBEACOPP) followed by pembrolizumab consolidation. All participants receive pembrolizumab monotherapy intravenous (IV) for 3 cycles (cycle length = 3 weeks (wks); up to 9 wks). All participants receive AVD IV for 2 cycles (cycle length = 4 wks; up to 8 wks) after Positron Emission Tomography (PET) 2. Participants who are PET 3 -ve, or +ve & age ≥ 60 years, receive up to 4 additional cycles of AVD IV (cycle length = 4 wks, up to 16 wks), or up to 4 cycles of escBEACOPP IV if PET 3 +ve, age <60 years; cycle length = 3 wks; up to 12 wks. All participants receive pembrolizumab consolidation IV for 4 cycles (cycle length = 6 wks; up to 24 wks). Total treatment duration is up to 57 wks. |
Biological: Pembrolizumab
200 mg IV administered on Day 1 of each 3-week cycle for 3 cycles during pembrolizumab monotherapy. 400 mg IV administered on Day 1 of each 6-week cycle for 4 cycles as pembrolizumab consolidation. Other Names:
Drug: Doxorubicin 25 mg/m^2 IV administered on Days 1 and 15 of each 4-week cycle for 2 cycles in all participants after PET2 and up to 4 additional cycles after PET3 (participants who are PET3 -ve, or +ve & ≥60 years of age). 35 mg/m^2 IV administered on Day 1 of each 3-week cycle for up to 4 cycles after PET3 (participants who are PET3 +ve, <60 years of age). Other Names:
Drug: Vinblastine 6 mg/m^2 IV administered on Days 1 and 15 of each 4-week cycle for 2 cycles after PET2 (all participants) and up to 4 additional cycles after PET3 (participants who are PET3 -ve, or +ve & ≥60 years of age).
Other Names:
Drug: Dacarbazine 375 mg/m^2 IV on Days 1 and 15 of each 4-week cycle for 2 cycles after PET2 (all participants) and up to 4 additional cycles after PET3 (participants who are PET3 -ve, or +ve & ≥60 years of age).
Other Name: Dtic-Dome® Drug: Bleomycin 10 units/m^2 IV administered on Day 8 of each 3-week cycle for up to 4 cycles after PET3 (participants who are PET3 +ve & <60 years of age).
Other Name: Blenoxane® Drug: Etoposide 200 mg/m^2 IV administered on Days 1-3 of each 3-week cycle for up to 4 cycles after PET3 (participants who are PET3 +ve & <60 years of age).
Other Names:
Drug: Cyclophosphamide 1250 mg/m^2 IV administered on Day 1 of each 3-week cycle for up to 4 cycles after PET3 (participants who are PET3 +ve & <60 years of age).
Other Names:
Drug: Vincristine 1.4 mg/m^2 IV on Day 8 of each 3-week cycle for up to 4 cycles after PET3 (participants who are PET3 +ve &<60 years of age).
Other Names:
Drug: Procarbazine 100 mg/m^2 orally (PO) administered on Days 1-7 of each 3-week cycle for up to 4 cycles after PET3 (participants who are PET3 +ve & <60 years of age).
Other Name: Matulane® Drug: Prednisone 40 mg/m^2 PO administered on Days 1-14 of each 3-week cycle for up to 4 cycles after PET3 (participants who are PET3 +ve & <60 years of age).
Other Names:
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Primary Outcome Measures :
- Complete Response (CR) at the End of Study Intervention as Assessed by Independent Central Review (ICR) Per Lugano 2014 Response Criteria [ Time Frame: Up to approximately 57 weeks ]The percentage of participants who have CR at the end of study intervention, after the completion of pembrolizumab consolidation, as assessed by ICR per Lugano 2014 response criteria will be presented.
Secondary Outcome Measures :
- CR at the End of Study Intervention as Assessed by Investigator Per Lugano 2014 Response Criteria [ Time Frame: Up to approximately 57 weeks ]The percentage of participants who have CR at the end of study intervention, after the completion of pembrolizumab consolidation, as assessed by the investigator per Lugano 2014 response criteria will be presented.
- Duration of Complete Response (DurCR) as Assessed by Independent Central Review Per Lugano 2014 Response Criteria [ Time Frame: Up to approximately 72 months ]DurCR is defined, only for the subgroup of participants who achieve CR, as the time from the first documentation of CR to disease progression or to death due to any cause, whichever comes first as assessed by the independent central review per Lugano 2014 response criteria.
- Positron Emission Tomography (PET) Negativity by Independent Central Review Per 3-Fluorodeoxyglucose (FDG)-PET 5-point Scale After Administration of Pembrolizumab Monotherapy [ Time Frame: Up to approximately 9 weeks ]The rate of PET negativity is defined as the percentage of participants with a score of 1, 2, or 3, assessed by independent central review according to the FDG-PET 5-point scale, after administration of pembrolizumab monotherapy. Per FDG-PET 5-point scale: Score 1= No uptake above the background, Score 2= Uptake ≤ mediastinum, Score 3= Uptake > mediastinum but ≤ liver, Score 4= Uptake moderately higher than liver, Score 5= Uptake markedly higher than liver or new lesions. In the present study, scores of 1, 2 and 3 are considered to be negative and scores of 4 and 5 are considered to be positive.
- PET Negativity by Independent Central Review Per FDG-PET 5-point Scale After Administration of Pembrolizumab Monotherapy and Chemotherapy [ Time Frame: Up to approximately 17 weeks ]The rate of PET negativity is defined as the percentage of participants with a score of 1, 2, or 3, assessed by independent central review according to the FDG-PET 5-point scale, after administration of pembrolizumab monotherapy and chemotherapy. Per FDG-PET 5-point scale: Score 1= No uptake above the background, Score 2= Uptake ≤ mediastinum, Score 3= Uptake > mediastinum but ≤ liver, Score 4= Uptake moderately higher than liver, Score 5= Uptake markedly higher than liver or new lesions. In the present study, scores of 1, 2 and 3 are considered to be negative and scores of 4 and 5 are considered to be positive.
- Number of Participants Who Experienced an Adverse Event (AE) [ Time Frame: Up to approximately 64 weeks ]An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE will be reported.
- Number of Participants Who Discontinued Study Treatment Due to an AE [ Time Frame: Up to approximately 57 weeks ]An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be reported.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
The main inclusion criteria include, but are not limited to the following:
- Has a histologically confirmed diagnosis of Ann Arbor Stage III or IV classical Hodgkin Lymphoma (cHL). Stage I and II participants may be enrolled, but must have at least one National Comprehensive Cancer Network (NCCN) unfavorable risk factor per protocol
- Has measurable 2-fluorodeoxyglucose (FDG)-avid disease based on investigator assessment according to Lugano 2014 response criteria
- Has not received prior radiation therapy, chemotherapy, immunotherapy, or other systemic therapy for the treatment of cHL before the first dose of study intervention
- Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 assessed within 7 days before the start of study intervention
Exclusion Criteria:
The main exclusion criteria include, but are not limited to the following:
- Has confirmed nodular lymphocyte-predominant Hodgkin Lymphoma (HL)
- Has an uncontrolled intercurrent cardiovascular illness
- Has received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-programmed cell death ligand 1 protein (PD-L1), or anti- programmed cell death ligand 2 protein (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
- Has received or is expected to receive a live or live-attenuated vaccine within 30 days before the first dose of study intervention
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
- Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
- Has radiographically detectable central nervous system metastases and/or carcinomatous meningitis
- Has an active autoimmune disease that has required systemic treatment in past 2 years
- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- Has a history or current evidence of pulmonary fibrosis
- Has had an allogenic tissue/solid organ transplant
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05008224
Locations
Show 48 study locations
Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
| Study Director: | Medical Director | Merck Sharp & Dohme LLC |
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Merck Sharp & Dohme LLC |
| ClinicalTrials.gov Identifier: | NCT05008224 |
| Other Study ID Numbers: |
3475-C11 MK-3475-C11 ( Other Identifier: Merck ) KEYNOTE-C11 ( Other Identifier: Merck ) 2021-001244-95 ( EudraCT Number ) |
| First Posted: | August 17, 2021 Key Record Dates |
| Last Update Posted: | July 14, 2022 |
| Last Verified: | June 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf |
| URL: | http://engagezone.msd.com/ds_documentation.php |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Merck Sharp & Dohme LLC:
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Programmed Cell Death 1 (PD-1, PD1) Programmed Cell Death-Ligand 1 (PD-L1, PDL1) Programmed Cell Death-Ligand 2 (PD-L2, PDL2) |
Additional relevant MeSH terms:
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Lymphoma Hodgkin Disease Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Prednisone Cyclophosphamide Dacarbazine Doxorubicin Pembrolizumab Etoposide Etoposide phosphate |
Vincristine Bleomycin Vinblastine Procarbazine Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antibiotics, Antineoplastic Topoisomerase II Inhibitors |