Fitness-adapted, Pembrolizumab-based Therapy for Untreated Classical Hodgkin Lymphoma Patients 60 Years of Age and Above
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|ClinicalTrials.gov Identifier: NCT05404945|
Recruitment Status : Recruiting
First Posted : June 3, 2022
Last Update Posted : July 29, 2022
This is a multi-center, open-label phase II study to assess the efficacy of a novel fitness-adapted regimen in previously untreated older patients with classical Hodgkin lymphoma. All participants will receive up to a total of 8 cycles of pembrolizumab (Q6 week dosing). The first cycle of pembrolizumab will be administered in combination with brentuximab vedotin (BV) ("lead-in treatment").
Following lead-in treatment, all participants will undergo interim PET/CT (iPET) as well as fitness testing to help inform participant level of fitness for subsequent lymphoma-directed therapies.
Participants deemed "non-fit" by this assessment will continue 3 additional 6 week cycles of concurrent pembrolizumab and BV ("induction therapy", each cycle is 42 days), then continue single-agent pembrolizumab to complete up to 4 additional cycles (i.e., 8 total) of therapy ("consolidation and maintenance therapy", Non-Fit cohort). Two additional BV doses will be given as consolidation, at days 1 and 22 of pembrolizumab cycle 5.
Those deemed "fit" after lead-in therapy (Fit cohort) will continue pembrolizumab and switch from BV to concurrently-administered combination chemotherapy using doxorubicin (A), vinblastine (V), and dacarbazine (D) for a total of 4 planned AVD cycles (3, 6-week pembrolizumab cycles, "induction therapy"). Chemotherapy drugs will be given at standard doses as in ABVD (no bleomycin will be given in this study) on days 1 and 15 of each 28-day cycle (C1AVD), and pembrolizumab dosing will remain every 42 days. Following end-induction PET/CT, pembrolizumab will continue every 42 days for up to 4 cycles in the consolidation/maintenance phase. Two additional BV doses will be given as consolidation, at days 1 and 22 of pembrolizumab cycle 5.
|Condition or disease||Intervention/treatment||Phase|
|Classical Hodgkin Lymphoma||Drug: Pembrolizumab Drug: Doxorubicin Drug: Vinblastine Drug: Dacarbazine Drug: Brentuximab vedotin||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||44 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Fitness-adapted, Pembrolizumab-based Therapy for Untreated Classical Hodgkin Lymphoma Patients 60 Years of Age and Above (cHL 001)|
|Actual Study Start Date :||July 26, 2022|
|Estimated Primary Completion Date :||October 3, 2027|
|Estimated Study Completion Date :||October 3, 2027|
Experimental: Fit Cohort
Three 6-week cycles of 400 mg intravenous pembrolizumab + intravenous AVD (q 2 weeks).
Pembrolizumab 400 mg IV
Doxorubicin 25mg/m2 IV
Other Name: Adriamycin
Vinblastine 6mg/m2 IV
Dacarbazine 375mg/m2 IV
Active Comparator: Non-Fit Cohort
Three 6-week cycles of 400 mg intravenous pembrolizumab and concurrent (q 3 week) intravenous brentuximab vedotin (BV).
Pembrolizumab 400 mg IV
Drug: Brentuximab vedotin
Brentuximab vedotin 1.8 mg/kg IV
- Complete Remission Rate [ Time Frame: 2 years ]Evaluate complete remission rate as defined by LYRIC criteria at end of induction in fit older participants with cHL following anthracycline-based chemotherapy.
- Incidence of grade 3-5 treatment-related AEs [ Time Frame: 2 years ]Assess tolerance and safety of a fitness-adapted pembrolizumab-based regimen in fit older participants with cHL based on incidence of grade 3-5 treatment-related AEs (CTCAE v5.0)
- 2-year PFS, 2-year OS, 2-year Lymphoma Specific Survival in the fit older population following pembrolizumab-based adaptive therapy [ Time Frame: 2 years ]Evaluate the efficacy, as determined by the 2-year progression free survival (PFS), overall survival (OS), and 2-year lymphoma specific survival in the fit older population.
- Complete remission rate (by LYRIC criteria), 2-year PFS, 2-year OS, 2-year Lymphoma Specific Survival in the non-fit older population [ Time Frame: 2 years ]Evaluate the efficacy of a chemotherapy-free approach (pembrolizumab plus BV), as determined by the complete remission rate (LYRIC criteria), 2-year progression free survival (PFS), overall survival (OS), and 2-year lymphoma specific survival in participants who are not fit for anthracycline-based therapy.
- Complete remission rate (LYRIC criteria) after lead-in BV/pembrolizumab [ Time Frame: 2 years ]Assess the efficacy of short course lead-in therapy and correlation with end-induction treatment efficacy for all participants.
- Incidence of grade 2-5 immune-related toxicities (CTCAE v5.0) [ Time Frame: 2 years ]Assess safety, as determined by the frequency of higher-grade immune-related adverse events for all participants.
- Rate of Indeterminate Response (LYRIC criteria) [ Time Frame: 2 years ]Assess the rate of "indeterminate response" by LYRIC criteria at interim and end-induction PET/CT and correlate with the presence of active Hodgkin lymphoma on biopsy (when available) and clinical outcome for all participants.
- Incidence of change in fitness assignment from baseline assessment. [ Time Frame: 2 years ]Evaluate and summarize incidence of changes in fitness assignments throughout therapy.
- Incidence and Severity of treatment-related toxicities [ Time Frame: 2 years ]Summarize participant fitness throughout therapy by incidence and severity of treatment-related toxicities.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05404945
|Contact: Dena Snyder||4349249969||DS6HE@hscmail.mcc.virginia.edu|
|United States, Virginia|
|University of Virginia||Recruiting|
|Charlottesville, Virginia, United States, 22911|
|Contact: Dena Snyder 434-924-9969 DS6HE@hscmail.mcc.virginia.edu|
|Principal Investigator: Craig Portell, MD|