Phase II Trial of Pembrolizumab Followed by Consolidation Radiotherapy in Patients with Early-Stage Favorable Classic Hodgkin Lymphoma

Trial ID: 2024-520138-31-00
Protocol: Uni-Koeln-5450
Sponsor: University Of Cologne

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Diseases & Conditions

Hodgkin's disease

Objectives

The primary objective is to evaluate the efficacy of pembrolizumab, an anti-PD-1 antibody, administered sequentially to consolidation radiotherapy in patients with early-stage favorable classic Hodgkin lymphoma. The secondary objectives include the assessment of safety and feasibility of the specified treatment regimen. 5

Participants

The sponsor did not provide the total number of participants. The study population consists of patients diagnosed with early-stage favorable classic Hodgkin lymphoma. Eligible participants include individuals aged between 18 and 75 years with a histologically confirmed first diagnosis. The disease must be classified as stage I-II without specific risk factors, such as a large mediastinal mass, extranodal involvement, elevated erythrocyte sedimentation rate, or involvement of three or more nodal areas. Inclusion requires an Eastern Cooperative Oncology Group performance status of 0 to 1 and an estimated life expectancy exceeding 3 months. Necessary hematological parameters include a hemoglobin level of at least 9 g/dL, a platelet concentration of at least 100 x 10⁹/L, and an absolute neutrophil count of at least 1.5 x 10⁹/L. The population includes both males and females, with specific requirements for contraception and pregnancy testing for individuals of childbearing potential.

Plans and Procedures

This Phase II exploratory study is designed to estimate the efficacy of pembrolizumab, an anti-PD-1 antibody, followed by consolidation radiotherapy in patients with early-stage favorable classic Hodgkin lymphoma. The research methodology involves an initial screening visit to confirm a histologically confirmed first diagnosis, assess stage I-II status without risk factors, and evaluate hematological parameters, ECOG performance status, and life expectancy. Following eligibility confirmation, participants receive pembrolizumab via intravenous infusion at a dose of 200 mg. The primary endpoint is progression-free survival at 1 year. Secondary endpoints include remission status, overall survival, event-free survival, and the monitoring of adverse events. The trial includes follow-up assessments to evaluate patient-reported outcomes and the rate of early discontinuation. The study is estimated to occur within a period spanning from 2026 to 2029.

Treatment

The experimental treatment consists of pembrolizumab, administered as a solution for infusion. The dosage is 200 mg via intravenous infusion.

The therapeutic regimen involves the administration of the anti-PD-1 antibody followed by consolidation radiotherapy in patients with early-stage favorable classic Hodgkin lymphoma.

Efficacy

The efficacy of the experimental treatment involving pembrolizumab followed by consolidation radiotherapy in patients with early-stage favorable classic Hodgkin lymphoma will be evaluated using specific endpoints. The primary endpoint is progression-free survival at 1 year.

Secondary efficacy assessments include:

Remission status following pembrolizumab therapy and consolidation radiotherapy.
Progression-free survival at 2 years.
Overall survival at 1 year and 2 years.
Event-free survival at 1 year and 2 years.
Patient-reported outcomes collected at baseline, during treatment, and during follow-up.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Histologically confirmed first diagnosis of cHL
Early-stage favorable cHL as assessed by all mandatory imaging examinations as outlined in section 5.1.2.3 of the protocol, i.e.stage I-II without risk factors: Large mediastinal mass; Extranodal involvement; Elevated erythrocyte sedimentation rate (ESR); Involvement of ≥ 3 nodal areas
Age ≥ 18 and ≤ 75 years on the day of signing the patient information and informed consent form (ICF)
Participants must be willing and capable of giving written informed consent prior to any trial-related activity
Adequate blood count (except for cHL-related changes or functional disorders) obtained within 7 days prior to signing the ICF: Hemoglobin (Hb) ≥ 9 g/dL (without red-blood-cell transfusion within the prior 7 days) ; Platelet concentration ≥ 100 x 109/L (without platelet transfusion within the prior 7 days) ; Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to signing the ICF
Estimated life expectancy > 3 months
Contraception a) Females of childbearing potential must have a negative urine or serum ß-human chorionic gonadotropin (ß-hCG) pregnancy test within 7 days prior to signing the ICF, not be breastfeeding and be willing to use a highly effective method of contraception as described below from enrollment to at least 6 months after the last dose of systemic trial treatment; b) Non-sterile males who are sexually active with WOCBP must be willing to use barrier methods such as a condom for effective contraception and refrain from sperm donation from enrollment to at least 6 months after the last dose of systemic trial treatment.

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Exclusion Criteria

Target disease exceptions: Knwon central nervous system lymphoma, subjects with nodular lymphocyte-predominant Hodgkin lymphoma or composite lymphoma
Prior cHL-directed treatment
Prior chemotherapy, RT or allogeneic stem cell/solid organ transplant
Prior or concurrent disease precluding protocol treatment
Abnormal laboratory test findings: a) Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection. Patients who receive an antiviral treatment and have no detectable hepatitis B virus (HBV)-DNA or hepatitis C virus (HCV)-RNA can be included in the trial; b) Serum creatinine > 1.5 x upper limit of normal (ULN) or creatinine clearance (CrCl) < 30 mL/min measured directly or calculated using the CKD-EPI formula; c) Aspartate aminotransferase/alanine aminotransferase (AST/ALT) > 2.5 x ULN. d) Total bilirubin > 1.5 x ULN unless the elevation is due to Gilbert’s syndrome h) International normalized ratio (INR) or prothrombin time (PT), activated partial thromboplastin time (aPTT) > 1.5 x ULN
Live vaccine or live-attenuated vaccine within 30 days before signing the ICF. Administration of killed vaccines is allowed.
Pregnancy or breastfeeding.
History of documented allergic reactions or acute hypersensitivity reaction to antibody treatment.
Known hypersensitivity or allergy to any of the excipients in the pembrolizumab formulation.
Current or prior participation in another interventional trial that could interact with this trial.
Lack of accountability and inability to appreciate the nature, meaning, and consequences of the trial and to formulate their own wishes correspondingly.
Non-compliance, for reasons including, but not limited to, the following: Drug dependency or substance abuse that would interfere with cooperation with requirements of the trial; Refusal of blood products during treatment; Any similar circumstances that appear to make compliance with any trial procedures impossible
Relationship of dependence or employer-employee relationship to the sponsor or the investigator.
Committal to an institution on judicial or official order.