Phase 2 Study of Pembrolizumab With Chemotherapy in Frail Patients With Newly Diagnosed Classical Hodgkin Lymphoma
Overview
- Phase
- Phase 2
- Status
- Not yet recruiting
- Sponsor
- City of Hope Medical Center
- Enrollment
- 23
- Locations
- 1
- Primary Endpoint
- Complete metabolic response (CMR) to pembrolizumab and gemcitabine (P-G)
Overview
Brief Summary
This phase II trial tests how well pembrolizumab in addition to chemotherapy (gemcitabine, brentuximab vedotin, and dacarbazine) works in treating frail patients with newly diagnosed Hodgkin lymphoma who aren't candidates for standard anthracycline-based treatment. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill cancer cells. Brentuximab vedotin is in a class of medications called antibody-drug conjugates. It is made of a monoclonal antibody called brentuximab that is linked to a cytotoxic agent called vedotin. Brentuximab attaches to CD30 positive lymphoma cells in a targeted way and delivers vedotin to kill them. Dacarbazine is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill cancer cells and slow down or stop cancer growth. Pembrolizumab in combination chemotherapy may be a safe and effective alternative treatment option for frail patients with Hodgkin lymphoma who can't receive standard anthracycline-based treatment.
Detailed Description
PRIMARY OBJECTIVE:
I. Estimate the best complete metabolic response (CMR) rate for frail patients with classical Hodgkin lymphoma (cHL) who receive pembrolizumab and gemcitabine (P-G).
SECONDARY OBJECTIVES:
I. Estimate CMR rate, overall response rate (ORR), progression-free-survival (PFS), duration of response (DOR), and overall response (OS) among patients who receive P-G (± pembrolizumab maintenance).
II. Estimate CMR, overall response, PFS, DOR, and OS among patients who receive pembrolizumab, brentuximab vedotin, and dacarbazine (P-BV-D).
III. Evaluate the toxicity of P-G, pembrolizumab maintenance, and P-BV-D.
EXPLORATORY OBJECTIVES:
I. Explore association between geriatric assessment measures (Cancer and Aging Research Group [CARG] geriatric assessment) and toxicity and efficacy in the elderly patients enrolled on this trial.
II. Assess functional trajectory determined by short physical performance battery (SPPB) change score in the elderly patients enrolled on this trial.
III. Explore the association between clinical outcomes and pathological tumor characteristics.
OUTLINE:
CYCLES 1-8: Patients receive pembrolizumab intravenously (IV) over 30 minutes and gemcitabine IV on day 1 of each cycle. Cycles repeat every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients without progressive disease during or at the completion of 8 cycles of P-G proceed to maintenance therapy. Patients with progressive disease during or at the completion of 8 cycles of P-G proceed to salvage therapy.
MAINTENANCE THERAPY: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 42 days for up to 4 cycles (cycles 9-12) in the absence of disease progression or unacceptable toxicity.
SALVAGE THERAPY: Patients receive pembrolizumab IV over 30 minutes, brentuximab vedotin IV over 30 minutes, and dacarbazine IV on day 1 of each cycle. Cycles repeat every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo positron emission tomography (PET)/computed tomography (CT) and collection of blood samples throughout the trial and may undergo echocardiography (ECHO) at screening if indicated.
After completion of study treatment, patients are followed up at 30 days and at 12, 18 (salvage patients), and 24 months.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Documented informed consent of the participant and/or legally authorized representative
- •Assent, when appropriate, will be obtained per institutional guidelines
- •Agreement to allow the use of archival tissue from diagnostic tumor biopsies
- •If unavailable, exceptions may be granted with study principal investigator (PI) approval
- •Meets at least one of the following criteria indicating unsuitability for conventional anthracycline-based frontline chemotherapy, as determined by the investigator:
- •Age ≥ 75 years
- •Eastern Cooperative Oncology Group (ECOG) 2-4
- •Left ventricular ejection fraction (LVEF) \< 50%
- •Creatinine clearance \< 60 mL/min, using Cockcroft-Gault formula or equivalent
- •Pulmonary function impairment: forced expiratory volume in 1 second (FEV1) \< 50% and/or diffusion capacity of the lung for carbon monoxide (DLCO) \< 50%
Exclusion Criteria
- •Concomitant investigational therapy
- •Live vaccine within 30 days prior to day 1 of protocol therapy (e.g. measles, mumps, rubella, varicella, yellow fever, rabies, Bacille Calmette Guerin \[BCG\], oral polio vaccine, and oral typhoid)
- •Grade ≥ 2 peripheral neuropathy
- •Requirement for hemodialysis or peritoneal dialysis. Estimated glomerular filtration rate (EGFR) \> 30 for pembrolizumab + BV + dacarbazine
- •Known active central nervous system (CNS) involvement by lymphoma including parenchymal and/or lymphomatous meningitis
- •History of prior ≥ grade 3 hypersensitivity to either brentuximab vedotin or pembrolizumab
- •Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
- •History of another primary malignancy that has been in remission for fewer than 3 years, with the following exceptions:
- •Non-melanoma skin cancer treated with curative intent
- •In situ cervical cancer
Arms & Interventions
Treatment (P-G, P-BV-D)
See Detailed Description.
Intervention: Biospecimen Collection (Procedure)
Treatment (P-G, P-BV-D)
See Detailed Description.
Intervention: Brentuximab Vedotin (Drug)
Treatment (P-G, P-BV-D)
See Detailed Description.
Intervention: Computed Tomography (Procedure)
Treatment (P-G, P-BV-D)
See Detailed Description.
Intervention: Dacarbazine (Drug)
Treatment (P-G, P-BV-D)
See Detailed Description.
Intervention: Echocardiography Test (Procedure)
Treatment (P-G, P-BV-D)
See Detailed Description.
Intervention: Gemcitabine (Drug)
Treatment (P-G, P-BV-D)
See Detailed Description.
Intervention: Pembrolizumab (Biological)
Treatment (P-G, P-BV-D)
See Detailed Description.
Intervention: Physical Performance Testing (Other)
Treatment (P-G, P-BV-D)
See Detailed Description.
Intervention: Positron Emission Tomography (Procedure)
Treatment (P-G, P-BV-D)
See Detailed Description.
Intervention: Pulmonary Function Test (Procedure)
Outcomes
Primary Outcomes
Complete metabolic response (CMR) to pembrolizumab and gemcitabine (P-G)
Time Frame: During/after cycles 1-8 of P-G (cycle length = 21 days), before initiation of salvage or maintenance therapy or non-protocol lymphoma therapy
Will be estimated by the proportion of response-evaluable patients achieving a best response of CMR, along with the 95% exact binomial confidence interval.
Secondary Outcomes
- Overall survival (OS)(From start of P-G treatment to time of death, assessed up to 24 months)
- Incidence of adverse events(Up to 24 months)
- CMR(During/after cycles 1-8 of P-G (cycle length = 21 days) or cycles 1-4 of pembrolizumab maintenance (cycle length = 42 days), before initiation of non-protocol lymphoma therapy)
- Overall response (OR)(During/after cycles 1-8 of P-G (cycle length = 21 days) or cycles 1-4 of pembrolizumab maintenance (cycle length = 42 days), before initiation of non-protocol lymphoma therapy)
- Progression-free survival (PFS)(From start of P-G treatment to time of disease relapse/progression or death, assessed up to 24 months)
- Duration of response (DOR)(From first achievement of CMR or PMR during/after cycles 1-8 of P-G (cycle length = 21 days) or cycles 1-4 of pembrolizumab maintenance (cycle length = 42 days) to disease relapse/progression or death, assessed up to 24 months)
- CMR (for patients who receive salvage therapy)(During/after cycles 1-12 of pembrolizumab, brentuximab vedotin, and dacarbazine (P-BV-D) (cycle length = 21 days), before initiation of non-protocol lymphoma therapy)
- OR (for patients who receive salvage therapy)(During/after cycles 1-12 of P-BV-D (cycle length = 21 days), before initiation of non-protocol lymphoma therapy)
- DOR (for patients who receive salvage therapy)(From first achievement of CMR or PMR during/after cycles 1-12 of P-BV-D (cycle length = 21 days) to disease relapse/progression or death, assessed up to 24 months)
- PFS (for patients who receive salvage therapy)(From start of P-BV-D treatment to time of disease relapse/progression or death, assessed up to 24 months)
- OS (for patients who receive salvage therapy)(From start of P-BV-D treatment to time of death, assessed up to 24 months)
- Incidence of adverse events (for patients who receive salvage therapy)(Up to 24 months)