Classical Hodgkin Lymphoma MedDRA version: 20.1 Level: LLT Classification code 10080208 Term: Classical Hodgkin lymphoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: KEYTRUDA (pembrolizumab, MK-3475)
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Pembrolizumab
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Concentration unit: m
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has a histologically confirmed diagnosis of Ann Arbor Stage III or IV cHL. Stage I and II patients may be enrolled, but must have at least one NCCN unfavorable risk factor 2. Has measurable FDG-avid disease based on investigator assessment according to Lugano 2014 response criteria 3. Has not received prior radiation therapy, chemotherapy, immunotherapy, or other systemic therapy(including investigational agents) for the treatment of cHL before the first dose of study intervention 4. Is male or female, at least 18 years of age, at the time of signing the informed consent 5. Male participants are eligible to participate if they agree to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is as follows: • Pembrolizumab: no contraception requirement • Chemotherapy: 90 days • Refrain from donating sperm PLUS either: • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR • Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause) as detailed below: - Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant • Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed 6. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: • Is not a WOCBP OR • Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period The length of time required to continue contraception for each study intervention is as follows: • Chemotherapy: 180 days • Pembrolizumab: 120 days The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention - A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 72 hours before the first dose of study intervention - If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive - The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy - Contraceptive use by women should be consistent with
Exclusion criteria
Exclusion criteria: 1. Has confirmed nodular lymphocyte-predominant HL 2. Has an uncontrolled intercurrent cardiovascular illness including, but not limited to the following: • Symptomatic congestive heart failure (ejection fraction lower than institutional LLN) • Unstable angina pectoris • Cardiac arrythmia 3. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137) 4. Has received or is expected to receive a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed 5. 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 6. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor 7. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years 8. Has radiographically detectable (even if asymptomatic and/or previously treated) central nervous system metastases and/or carcinomatous meningitis as assessed by investigator at the time of diagnosis 9. Has severe hypersensitivity (=Grade 3) to any of the study interventions or their excipients 10. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed 11. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease 12. Has a history or current evidence of pulmonary fibrosis 13. Has an active infection requiring systemic therapy 14. Has a known history of HIV infection. No HIV testing is required unless mandated by local health authority 15. Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection 16. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator 17. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study 18. Has any contraindication to the use of any of the chemotherapeutic agents used in the study 19. Has not recovered adequately from surgery and/or any complications from the surgery 20. Has had an allogenic tissue/solid organ transplant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To evaluate complete response (CR) rate at the end of study intervention in participants with newly diagnosed classical Hodgkin Lymphoma (cHL) assessed by independent central review according to Lugano 2014 response criteria;Secondary Objective: 1. Evaluate the CR rate at the end of study intervention in participants with newly diagnosed cHL by investigator assessment according to Lugano 2014 response criteria 2. Evaluate the duration of complete response (DurCR) in participants with newly diagnosed cHL by independent central review according to Lugano 2014 response criteria 3. Evaluate the rate of Positron Emission Tomography (PET) negativity at PET2 following 3 cycles of pembrolizumab monotherapy by independent central review according to the 2-flurodeoxyglucose(FDG)-PET 5-point scale 4. Evaluate the rate of PET negativity at PET3 after completion of 3 cycles of pembrolizumab monotherapy followed by 2 cycles of doxorubicin in combination with vinblastine and dacarbazine (AVD) by independent central review according to the FDG-PET 5-point scale 5. Evaluate the safety and tolerability of initial pembrolizumab monotherapy followed by chemotherapy and pembrolizumab consolidation in participants with newly diagnosed cHL;Primary end point(s): 1. Complete Response (CR) at the End of Study Intervention as Assessed by Independent Central Review Per Lugano 2014 Response Criteria;Timepoint(s) of evaluation of this end point: 1. Up to approximately 57 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. CR at the End of Study Intervention as Assessed by Investigator Per Lugano 2014 Response Criteria 2. Duration of Complete Response (DurCR) as Assessed by Independent Central Review Per Lugano 2014 Response Criteria 3. Positron Emission Tomography (PET) Negativity by Independent Central Review Per 2-Fluorodeoxyglucose (FDG)-PET 5-point Scale After Administration of Pembrolizumab Monotherapy 4. PET Negativity by Independent Central Review Per FDG-PET 5-point Scale After Administration of Pembrolizumab Monotherapy and Chemotherapy 5. Number of Participants Who Experienced an Adverse Event (AE) 6. Number of Participants Who Discontinued Study Treatment Due to an AE;Timepoint(s) of evaluation of this end point: 1. Up to approximately 57 weeks 2. Up to approximately 72 months 3. Up to approximately 9 weeks 4. Up to approximately 17 weeks 5. Up to approximately 64 weeks 6. Up to approximately 57 weeks | — |
Countries
Australia, Brazil, Canada, Chile, France, Israel, Italy, Poland, Russian Federation, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactInvestigación Clínica
Merck Sharp & Dohme de España SA
Outcome results
None listed