Fitness-adapted, Pembrolizumab-based Therapy for Untreated Classical Hodgkin Lymphoma Patients 60 Years of Age and Above

NCT05404945 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: cHL001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

Brief Summary

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 "Frail" 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", Frail 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. Participants deemed "unfit" after lead-in therapy and by fitness assessment will continue pembrolizumab and switch from BV to concurrently administered combination chemotherapy termed "mini-avd" as induction therapy. Mini-avd consists of lower doses of conventional AVD chemotherapy (doxorubicin, vinblastine and dacarbazine) and will be administered for on days 1 and 15 of a 28 day cycle for 4 planned cycles. Pembrolizumab will continue 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.

Conditions

Classical Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• Complete Remission Rate

  Evaluate complete remission rate as defined by LYRIC criteria at end of induction in fit and unfit older participants with cHL following anthracycline-based chemotherapy.

  2 years

• Incidence of grade 3-5 treatment-related AEs

  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 years

Secondary Outcomes (4)

• 2-year PFS, 2-year OS, 2-year Lymphoma Specific Survival in the fit older population following pembrolizumab-based adaptive therapy

  2 years

• Complete remission rate (by LYRIC criteria), 2-year PFS, 2-year OS, 2-year Lymphoma Specific Survival in the Frail older population

  2 years

• Complete remission rate (LYRIC criteria) after lead-in BV/pembrolizumab

  2 years

• Incidence of grade 2-5 immune-related toxicities (CTCAE v5.0)

  2 years

Other Outcomes (3)

• Rate of Indeterminate Response (LYRIC criteria)

  2 years

• Incidence of change in fitness assignment from baseline assessment.

  2 years

• Incidence and Severity of treatment-related toxicities

  2 years

Study Arms (3)

Fit Cohort

EXPERIMENTAL

Three 6-week cycles of 400 mg intravenous pembrolizumab + intravenous AVD (q 2 weeks).

Drug: Pembrolizumab; Drug: Doxorubicin; Drug: Vinblastine; Drug: Dacarbazine; Drug: Brentuximab vedotin

Frail Cohort

ACTIVE COMPARATOR

Three 6-week cycles of 400 mg intravenous pembrolizumab and concurrent (q 3 week) intravenous brentuximab vedotin (BV).

Drug: Pembrolizumab; Drug: Doxorubicin; Drug: Vinblastine; Drug: Dacarbazine; Drug: Brentuximab vedotin

Unfit Cohort

ACTIVE COMPARATOR

Three 6-week cycles of 400 mg intravenous pembrolizumab and mini-AVD (q 2 weeks).

Drug: Pembrolizumab; Drug: Doxorubicin; Drug: Vinblastine; Drug: Dacarbazine; Drug: Brentuximab vedotin

Interventions

Pembrolizumab DRUG

Pembrolizumab 400 mg IV

Fit Cohort; Frail Cohort; Unfit Cohort

Doxorubicin DRUG

Doxorubicin 25mg/m2 IV

Also known as: Adriamycin

Fit Cohort; Frail Cohort; Unfit Cohort

Vinblastine DRUG

Vinblastine 6mg/m2 IV

Fit Cohort; Frail Cohort; Unfit Cohort

Dacarbazine DRUG

Dacarbazine 375mg/m2 IV

Fit Cohort; Frail Cohort; Unfit Cohort

Brentuximab vedotin DRUG

Brentuximab vedotin 1.8 mg/kg IV

Fit Cohort; Frail Cohort; Unfit Cohort

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants of any sex who are ≥60 years of age on day 1, cycle 1.
• The participant must be willing and able to provide written informed consent for the trial and participate in all planned study procedures.
• Histologically confirmed diagnosis of classical Hodgkin lymphoma
• PET-avid, measurable disease (≥1.5cm bi-dimensional measurement)
• Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to
• PS 2 may be allowed at the discretion of the treating investigator if impairment is considered to be primarily lymphoma-related. Evaluation of ECOG is to be performed within 10 days prior to the date of registration.
• Participants who have received involved field radiation will be allowed. However, they will be excluded if any of the following are true:
• Radiation was dosed ≤6 months from registration.
• Radiation was delivered to \> 1 lymph node group as defined by the NCCN criteria.
• The radiation dose was ≥30 Gy.
• The participant has radiation-related toxicities ≥ Grade 2 at the time of registration.
• The participant requires corticosteroids for radiation-related toxicities at the time of registration (regardless of dose).
• The participant has ever experienced radiation pneumonitis.
• Have adequate organ function as defined per protocol. Specimens must be collected within 10 days prior to registration (confirmation of eligibility).

You may not qualify if:

• Nodular lymphocyte-predominant Hodgkin lymphoma
• Life expectancy \< 6 months for any reason excluding lymphoma
• Has received prior therapy with an immune checkpoint inhibitor, against targets including but not limited to PD1, PDL1, PDL2, CTLA-4, OX40, or LAG 3 unless given with curative intent for reasons other than lymphoma AND the last dose was more than 3 years from registration. Any participant who received prior immune checkpoint inhibitor therapy will be excluded if they experienced any toxicity related to or possibly related to the immunotherapy that required discontinuation of drug.
• Prior systemic therapy for cHL, with the exception of steroids
• If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Presence of Grade ≥ 2 sensory and/or motor neuropathy
• Prior solid organ or stem cell transplant.
• Clinical suspicion or evidence of active involvement of lymphoma into the spinal cord, cerebral spinal fluid, or brain. External compression of the spinal cord or nerve roots is not considered involvement.
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines, subunit vaccines, and nucleic acid vaccines is allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent \[excluding steroids needed for lymphoma related symptoms\]) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (excluding carcinoma in situ of the bladder) that have undergone potentially curative therapy are not excluded.
• Has known severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. 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, etc.) is not considered a form of systemic treatment.

Sponsors & Collaborators

• University of Virginia: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (3)

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08902-2681, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Virginia

Charlottesville, Virginia, 22911, United States

Location

MeSH Terms

Interventions

pembrolizumab; Doxorubicin; Vinblastine; Dacarbazine; Brentuximab Vedotin

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: May 22, 2022
• First Posted: June 3, 2022
• Study Start: July 26, 2022
• Primary Completion (Estimated): October 3, 2027
• Study Completion (Estimated): October 3, 2027
• Last Updated: May 14, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)