Pembrolizumab in Combination With Salvage Chemotherapy for First-relapsed or Refractory Classical Hodgkin Lymphoma

Study Overview
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Brief Summary
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The aim of this trial is to develop an effective and well-tolerated regimen for treatment of r/r cHL by introducing the anti-PD-1 antibody pembrolizumab and adding it to well-established chemotherapy regimens (ICE, DHAP). Synergistic effects of conventional agents with checkpoint inhibition may facilitate a highly effective therapy with limited toxicity, which might eventually substitute the very toxic high-dose chemotherapy (HDCT).

Official Title
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Phase II Trial of Pembrolizumab in Combination With Salvage Chemotherapy for First-relapsed or Refractory Classical Hodgkin Lymphoma

Conditions
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Classical Hodgkin Lymphoma

Intervention / Treatment
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* Drug: Pembrolizumab plus Chemotherapy (ICE or DHAP)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed first relapse of cHL or primary refractory cHL Exclusion Criteria: Nodular lymphocyte-predominant Hodgkin lymphoma or composite lymphoma

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pembrolizumab plus Chemotherapy<br>All patients will receive 1 dose of 200 mg pembrolizumab IV as single agent upfront, followed by 2 cycles of IV P-ICE (pembrolizumab, ifosfamide, carboplatin, etoposide) and a PET/CT-based restaging. Following a PET-guided treatment strategy, patients will then receive either another 2 cycles of IV P-ICE in case of a negative PET (i.e., Deauville score 1-3), or 2 to 4 cycles of IV P-DHAP (pembrolizumab, dexamethasone, cytarabine, cisplatin) in case of a positive PET (i.e., Deauville score > 3). After completion of treatment with P-ICE or P-DHAP, respectively, patients will receive a consolidation therapy with pembrolizumab for another 6 cycles. In case of non-CR after at least 4 cycles of combination therapy (4x P-ICE or 2x P-ICE + 2x P-DHAP), physicians may decide to go for HDCT or an alternative standard of care treatment option. | Drug: Pembrolizumab plus Chemotherapy (ICE or DHAP)<br>* Pembrolizumab (200mg) alone or in combination with ICE (or DHAP in case of PET positive findings after P-ICE) will be admistered. 6 additional courses of pembrolizumab will be administered after the completion P-ICE or P-DHAP<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Metabolic Response Rate (CMR) | The proportion of patients with a Deauville score of 1-3 in the centrally reviewed restaging after treatment with 1 x pembrolizumab + 4 cycles of pembrolizumab and chemotherapy combined (4x P-ICE or 2x P-ICE + 2x P-DHAP) | after completion of P+chemotherapy, an average of 3 months |