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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05008224




Registration number
NCT05008224
Ethics application status
Date submitted
13/08/2021
Date registered
17/08/2021

Titles & IDs
Public title
Study of Safety and Efficacy of Pembrolizumab and Chemotherapy in Participants With Newly Diagnosed Classical Hodgkin Lymphoma (cHL) (MK-3475-C11/KEYNOTE-C11)
Scientific title
Phase 2 Study of Pembrolizumab and Chemotherapy in Patients With Newly Diagnosed Classical Hodgkin Lymphoma (KEYNOTE-C11)
Secondary ID [1] 0 0
MK-3475-C11
Secondary ID [2] 0 0
3475-C11
Universal Trial Number (UTN)
Trial acronym
KEYNOTE-C11
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Classical Hodgkin Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Hodgkin's

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Pembrolizumab
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Vinblastine
Treatment: Drugs - Dacarbazine
Treatment: Drugs - Bleomycin
Treatment: Drugs - Etoposide
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Vincristine
Treatment: Drugs - Procarbazine
Treatment: Drugs - Prednisone

Experimental: Pembrolizumab Monotherapy + AVD Chemotherapy/escBEACOPP Chemotherapy + Pembrolizumab Consolidation - After completing Positron Emission Tomography (PET) scan 1 during eligibility screening, participants received pembrolizumab monotherapy intravenous (IV) for three 3-week cycles followed by PET scan 2.

Participants next received 2 phases of chemotherapy. In chemotherapy phase 1, all participants received doxorubicin in combination with vinblastine \& dacarbazine (AVD) IV for two 4-week cycles followed by PET scan 3. In chemotherapy phase 2, participants who were PET scan 3 negative, or positive and age =60 years, received up to 4 additional cycles of AVD IV, while participants who were PET scan 3 positive and age \<60 years received up to four 3-week cycles of escalated bleomycin in combination with etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, \& prednisone (escBEACOPP) IV.

All participants then received pembrolizumab consolidation IV for four 6-week cycles followed by a final PET scan.


Treatment: Other: 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.

Treatment: Drugs: Doxorubicin
25 mg/m\^2 IV administered as part of AVD chemotherapy on Days 1 and 15 of each 4-week cycle for 2 cycles in all participants after PET scan 2 and up to 4 additional cycles after PET scan 3 (participants who are PET scan 3 negative, or positive and =60 years of age).

35 mg/m\^2 IV administered as part of escBEACOPP chemotherapy on Day 1 of each 3-week cycle for up to 4 cycles after PET scan 3 (participants who are PET scan 3 positive, \<60 years of age).

Treatment: Drugs: Vinblastine
6 mg/m\^2 IV administered as part of AVD chemotherapy on Days 1 and 15 of each 4-week cycle for 2 cycles after PET scan 2 (all participants) and up to 4 additional cycles after PET scan 3 (participants who are PET scan 3 negative, or positive and =60 years of age).

Treatment: Drugs: Dacarbazine
375 mg/m\^2 IV administered as part of AVD chemotherapy on Days 1 and 15 of each 4-week cycle for 2 cycles after PET scan 2 (all participants) and up to 4 additional cycles after PET scan 3 (participants who are PET scan 3 negative, or positive and =60 years of age).

Treatment: Drugs: Bleomycin
10 units/m\^2 IV administered as part of escBEACOPP chemotherapy on Day 8 of each 3-week cycle for up to 4 cycles after PET scan 3 (participants who are PET scan 3 positive and \<60 years of age).

Treatment: Drugs: Etoposide
200 mg/m\^2 IV administered as part of escBEACOPP chemotherapy on Days 1-3 of each 3-week cycle for up to 4 cycles after PET scan 3 (participants who are PET scan 3 positive and \<60 years of age).

Treatment: Drugs: Cyclophosphamide
1250 mg/m\^2 IV administered as part of escBEACOPP chemotherapy on Day 1 of each 3-week cycle for up to 4 cycles after PET scan 3 (participants who are PET scan 3 positive and \<60 years of age).

Treatment: Drugs: Vincristine
1.4 mg/m\^2 IV administered as part of escBEACOPP chemotherapy on Day 8 of each 3-week cycle for up to 4 cycles after PET scan 3 (participants who are PET scan 3 positive and \<60 years of age).

Treatment: Drugs: Procarbazine
100 mg/m\^2 orally (PO) administered as part of escBEACOPP chemotherapy on Days 1-7 of each 3-week cycle for up to 4 cycles after PET scan 3 (participants who are PET scan 3 positive and \<60 years of age).

Treatment: Drugs: Prednisone
40 mg/m\^2 PO administered as part of escBEACOPP chemotherapy on Days 1-14 of each 3-week cycle for up to 4 cycles after PET scan 3 (participants who are PET scan 3 positive and \<60 years of age).
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Complete Response (CR) Rate at the End of Study Intervention as Assessed by Blinded Independent Central Review (BICR) Per Lugano 2014 Response Criteria
Assessment method [1] 0 0
CR rate was assessed by BICR using Computed Tomography (CT) and PET scan according to Lugano 2014 response criteria (Cheson, B.D. et al, Journal of Clinical Oncology, 2014). At each timepoint, CR was determined by combining the anatomic response, metabolic response, and clinical data. The criteria for CR included complete metabolic (no/minimal 2-fluorodeoxyglucose \[FDG\] uptake) and radiologic response (target lesions regress to =1.5 cm in longest transverse diameter of a lesion) and no new lesions. Per protocol, participants who discontinued study intervention during pembrolizumab monotherapy, chemotherapy, or pembrolizumab consolidation, or are lost to follow-up, or receive any new non-study anticancer therapy prior to end of treatment were classified as non-responders. The percentage of participants who had CR after the completion of pembrolizumab consolidation is presented.
Timepoint [1] 0 0
Up to approximately 24 months
Secondary outcome [1] 0 0
CR Rate at the End of Study Intervention as Assessed by Investigator Per Lugano 2014 Response Criteria
Assessment method [1] 0 0
CR rate was assessed by the investigator using CT and PET scan according to Lugano 2014 response criteria (Cheson, B.D. et al, Journal of Clinical Oncology, 2014). At each timepoint, CR was determined by combining the anatomic response, metabolic response, and clinical data. The criteria for CR included complete metabolic (no/minimal FDG uptake) and radiologic response (target lesions regress to =1.5 cm in longest transverse diameter of a lesion) and no new lesions. Per protocol, participants who discontinued study intervention during pembrolizumab monotherapy, chemotherapy, or pembrolizumab consolidation, or are lost to follow-up, or receive any new non-study anticancer therapy prior to end of treatment were classified as non-responders. The percentage of participants who had CR after the completion of pembrolizumab consolidation is presented.
Timepoint [1] 0 0
Up to approximately 31 months
Secondary outcome [2] 0 0
Duration of Complete Response (DurCR) as Assessed by BICR Per Lugano 2014 Response Criteria
Assessment method [2] 0 0
DurCR was defined as the time from CR to progressive disease (PD) or death due to any cause, whichever came first. CR was assessed by BICR using CT and PET scan according to Lugano 2014 response criteria (Cheson, B.D. et al, Journal of Clinical Oncology, 2014). At each timepoint, CR was determined by combining the anatomic response, metabolic response, and clinical data. The criteria for CR included complete metabolic (no/minimal FDG uptake) and radiologic response (target lesions regress to =1.5 cm in longest transverse diameter of a lesion) and no new lesions. PD was defined as uptake moderately or markedly higher than the liver and/or new lesions. DurCR was analyzed by the Kaplan-Meier method for censored data and is presented for participants who demonstrated CR.
Timepoint [2] 0 0
Up to approximately 31 months
Secondary outcome [3] 0 0
Rate of PET Negativity Assessed by BICR According to the FDG-PET 5-point Scale After Administration of Pembrolizumab Monotherapy (PET Scan 2)
Assessment method [3] 0 0
The rate of PET negativity was defined as the percentage of participants considered negative on the FDG-PET 5-point scale, as assessed by BICR according to Lugano 2014 response criteria (Cheson, B.D. et al, Journal of Clinical Oncology, 2014). Participants were assigned a single score on the FDG-PET 5-point scale measuring FDG uptake (1 = no uptake above background, 2 = uptake above background but = mediastinum, 3 = uptake \> mediastinum but = liver, 4 = uptake moderately \> liver, 5 = uptake markedly \> liver or new FDG-positive lesions). Higher scores corresponded to greater uptake (greater disease). FDG-PET 5-point scale scores of 1, 2, and 3 were considered negative and scores of 4 and 5 were considered positive. The percentage of participants who were assessed as negative at PET scan 2, after completion of 3 cycles of pembrolizumab monotherapy, is presented.
Timepoint [3] 0 0
Up to approximately 10 weeks
Secondary outcome [4] 0 0
Rate of PET Negativity Assessed by BICR According to the FDG-PET 5-point Scale After Administration of Pembrolizumab Monotherapy and AVD Chemotherapy (PET Scan 3)
Assessment method [4] 0 0
The rate of PET negativity was defined as the percentage of participants considered negative on the FDG-PET 5-point scale, as assessed by BICR according to Lugano 2014 response criteria (Cheson, B.D. et al, Journal of Clinical Oncology, 2014). Participants were assigned a single score on the FDG-PET 5-point scale measuring FDG uptake (1 = no uptake above background, 2 = uptake above background but = mediastinum, 3 = uptake \> mediastinum but = liver, 4 = uptake moderately \> liver, 5 = uptake markedly \> liver or new FDG-positive lesions). Higher scores corresponded to greater uptake (greater disease). FDG-PET 5-point scale scores of 1, 2, and 3 were considered negative and scores of 4 and 5 were considered positive. The percentage of participants who were assessed as negative at PET scan 3, after completion of 3 cycles of pembrolizumab monotherapy and phase 1 AVD chemotherapy (2 AVD cycles), is presented.
Timepoint [4] 0 0
Up to approximately 5 months
Secondary outcome [5] 0 0
Number of Participants Who Experienced an Adverse Event (AE)
Assessment method [5] 0 0
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. Per protocol, collection and reporting of AEs was based on the study treatment received by the participant (pembrolizumab, AVD chemotherapy, or escBEACOPP chemotherapy) at the time of the event. The number of participants who experienced an AE is reported.
Timepoint [5] 0 0
Up to approximately 31 months
Secondary outcome [6] 0 0
Number of Participants Who Discontinued Study Treatment Due to an AE
Assessment method [6] 0 0
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. Per protocol, collection and reporting of AEs was based on the study treatment received by the participant (pembrolizumab, AVD chemotherapy, or escBEACOPP chemotherapy) at the time of the event. The number of participants who discontinued study intervention due to an AE is reported.
Timepoint [6] 0 0
Up to approximately 17 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/10/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/05/2024
Sample size
Target
Accrual to date
Final
146
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Liverpool Hospital-Haematology ( Site 0906) - Liverpool
Recruitment hospital [2] 0 0
Mater Misericordiae Limited ( Site 0904) - Brisbane
Recruitment hospital [3] 0 0
Princess Alexandra Hospital-Division of Cancer Services Trials Unit ( Site 0907) - Woolloongabba
Recruitment hospital [4] 0 0
Monash Health-Haematology Research ( Site 0908) - Clayton
Recruitment hospital [5] 0 0
Peter MacCallum Cancer Centre ( Site 0905) - Melbourne
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
4101 - Brisbane
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
3168 - Clayton
Recruitment postcode(s) [5] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Nevada
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
Canada
State/province [6] 0 0
Alberta
Country [7] 0 0
Canada
State/province [7] 0 0
Quebec
Country [8] 0 0
Chile
State/province [8] 0 0
Araucania
Country [9] 0 0
Chile
State/province [9] 0 0
Region M. De Santiago
Country [10] 0 0
France
State/province [10] 0 0
Aquitaine
Country [11] 0 0
France
State/province [11] 0 0
Bretagne
Country [12] 0 0
France
State/province [12] 0 0
Cote-d Or
Country [13] 0 0
France
State/province [13] 0 0
Rhone
Country [14] 0 0
France
State/province [14] 0 0
Seine-Maritime
Country [15] 0 0
Israel
State/province [15] 0 0
Haifa
Country [16] 0 0
Israel
State/province [16] 0 0
Jerusalem
Country [17] 0 0
Israel
State/province [17] 0 0
Ramat Gan
Country [18] 0 0
Israel
State/province [18] 0 0
Safed
Country [19] 0 0
Israel
State/province [19] 0 0
Tel Aviv
Country [20] 0 0
Italy
State/province [20] 0 0
Lombardia
Country [21] 0 0
Italy
State/province [21] 0 0
Milano
Country [22] 0 0
Italy
State/province [22] 0 0
Bologna
Country [23] 0 0
Italy
State/province [23] 0 0
Roma
Country [24] 0 0
Poland
State/province [24] 0 0
Mazowieckie
Country [25] 0 0
Poland
State/province [25] 0 0
Opolskie
Country [26] 0 0
Poland
State/province [26] 0 0
Pomorskie
Country [27] 0 0
Russian Federation
State/province [27] 0 0
Moskva
Country [28] 0 0
Russian Federation
State/province [28] 0 0
Sankt-Peterburg
Country [29] 0 0
Spain
State/province [29] 0 0
Barcelona
Country [30] 0 0
Spain
State/province [30] 0 0
Madrid
Country [31] 0 0
Turkey
State/province [31] 0 0
Izmir
Country [32] 0 0
Turkey
State/province [32] 0 0
Ankara
Country [33] 0 0
Turkey
State/province [33] 0 0
Istanbul

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

TypeOther DetailsAttachment
Study protocol Study Protocol and Statistical Analysis Plan
Statistical analysis plan Study Protocol and Statistical Analysis Plan



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT05008224