E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or refractory classical Hodgkin lymphoma |
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E.1.1.1 | Medical condition in easily understood language |
A cancer of the lymph glands that improved and then returned or did not improve in patients given with the usual treatments for this cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare progression free survival (PFS) as assessed by blinded independent central review according to the American Society of Clinical Oncology International Working Group (IWG) response criteria [Cheson, 2007] between the treatment arms (pembrolizumab or brentuximab vedotin).
To compare overall survival (OS) between treatment arms.
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E.2.2 | Secondary objectives of the trial |
To compare the complete remission rate (CRR) as assessed by blinded independent central review according to the IWG response criteria [Cheson, 2007] between treatment arms.
To compare the overall response rate (ORR) as assessed by blinded independent central review according to the IWG response criteria [Cheson, 2007] between treatment arms.
To evaluate PFS, CRR, and ORR as assessed by the investigator according to the IWG response criteria [Cheson, 2007] by treatment arm.
To evaluate the safety and tolerability of pembrolizumab.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Merck will conduct Future Biomedical Research on DNA (blood) specimens collected during this clinical trial if the subject consents to participate in this research. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time. |
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E.3 | Principal inclusion criteria |
– ≥18 years of age
– Relapsed or refractory classical Hodgkin lymphoma
– Measurable disease on spiral computed tomography (CT)
– Evaluable core or excisional lymph node biopsy
– Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
– Adequate organ function (laboratory studies)
– Negative pregnancy/lactation
– Adequate contraception (males and females)
Refer to the protocol for more detail on each inclusion criterion.
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E.4 | Principal exclusion criteria |
– Previous brentuximab vedotin
– Current study of an investigational agent
– Immunosuppressed
– Monoclonal antibody (mAB) within 4 weeks prior to first dose
– Allogeneic hematopoietic stem cell transplantation ≤5 years
– Known additional malignancy
– Active autoimmune disease, non-infectious pneumonitis, or central nervous system (CNS) metastases
– Known psychiatric or substance abuse disorders
– Prior therapy with antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
– anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD30, anti-CD137, or CTLAï€4 antibody
– HIV, hepatitis B (HBV), or hepatitis C (HCV)
– live vaccine within 30 days prior to first dose
Refer to the protocol for more detail on each exclusion criterion.
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E.5 End points |
E.5.1 | Primary end point(s) |
The efficacy objective of this trial is to compare the anti-tumor activity of 200-mg pembrolizumab versus 1.8 mg/kg brentuximab vedotin in subjects with relapsed or refractory diagnosed classical Hodgkin lymphoma (HL) who have not been previously treated with brentuximab vedotin.
The primary efficacy endpoints in this trial will be progression free survival (PFS) as assessed by blinded independent central review and defined as the time from randomization to the first documentation of lymphoma progression or death as a result of any cause [Cheson, 2007] and overall survival (OS) as a co primary endpoint.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
An interim PFS analysis is planned 3 months after all subjects are enrolled and 110 PFS events are observed (approximately 15 months after trial starts).
A final PFS analysis is planned after 221 PFS events are observed (approximately 21 months after trial starts).
An interim OS analysis is planned after 91 OS events (anticipated at 21 months).
A final OS analysis is planned after 146 OS events are observed (approximately 35 months after the trial starts).
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E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints in this trial will be CRR and ORR as assessed by blinded independent central review and PFS, CRR, and ORR as assessed by the investigator according to IWG response criteria [Cheson, 2007].
Safety will be assessed by reported adverse events (AEs) using the Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0. The safety endpoints include any AE, Grade 3-5 AE, serious AE, drug-related AE, serious and drug-related AE, Grade 3-5 and drug-related AE, dose modification due to AE, discontinuation due to AE, and death. Specific AEs and system organ classes (SOCs) (including ≥4 subjects in one of the treatment groups), specific AEs and SOCs (incidence <4 subjects in all of the treatment groups), and change from baseline results (laboratory tests, electrocardiograms, and vital signs) will also be included.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All secondary efficacy endpoints will be evaluated as part of the trial’s final analyses.
Safety endpoints will be evaluated at each of time points specified for the primary efficacy endpoints.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Brazil |
Canada |
Colombia |
Czech Republic |
Finland |
France |
Germany |
Israel |
Italy |
Japan |
Poland |
Russian Federation |
Singapore |
Spain |
Sweden |
Turkey |
Ukraine |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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If it is the last visit of the last subject, please enter "LVLS". If it is not LVLS provide the definition: LVLS |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 34 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 34 |