This phase I trial studies the side effects and the best dose of everolimus when given together with brentuximab vedotin in treating patients with Hodgkin lymphoma that has come back (relapsed) or is not responding to treatment (refractory). Everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Brentuximab vedotin may interfere with the ability of cancer cells to grow and spread by binding to a protein on the surface of cancer cells and then releasing a cancer-killing substance to them. Giving everolimus together with brentuximab vedotin may be a better treatment for Hodgkin lymphoma.
PRIMARY OBJECTIVES: I. To determine the safety and optimal dose of everolimus given in combination with brentuximab vedotin in relapsed or refractory Hodgkin lymphoma patients. SECONDARY OBJECTIVES: I. To determine the efficacy of everolimus in combination with brentuximab vedotin in relapsed or refractory Hodgkin lymphoma. II. To evaluate duration of response, progression free survival, and overall survival. III. To evaluate response by positron emission tomography (PET)-computed tomography (CT) based response criteria. TERTIARY OBJECTIVES: I. To assess cytokines and free light chain before and after therapy. OUTLINE: This is a dose-escalation study of everolimus. Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1 and everolimus orally (PO) once daily (QD) or every other day (QOD) on days 1-21. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity. Patients then receive brentuximab vedotin IV over 30 minutes on day 1 and everolimus PO QD or every other day on days 1-84 for 1 course. MAINTENANCE THERAPY: Beginning on course 17, patients receive everolimus PO QD, QOD, twice weekly, or thrice weekly on days 1-84. Courses repeat every 84 days in the absence of disease progression and unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for 1 year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Mayo Clinic
Rochester, Minnesota, United States
Maximum tolerated dose (MTD) of everolimus in combination with brentuximab vedotin, graded by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
MTD defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients).
Time frame: 21 days
Complete response (CR) rate
The CR rate will be estimated by the number of patients with an objective status of CR divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true complete response rate will be calculated.
Time frame: Up to 1 year
Duration of response
If an adequate number of events are seen, the distribution of duration of response will be estimated using the method of Kaplan-Meier. Otherwise, duration of response will be summarized descriptively.
Time frame: From date at which the patient's objective status is first noted to be a CR or PR to the earliest date progression is documented, assessed up to 1 year
Overall response rate (ORR) (complete response [CR] or partial response [PR])
The ORR will be estimated by the number of patients with an objective status of CR or PR divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true overall response rate will be calculated.
Time frame: Up to 1 year
Progression-free survival
The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.
Time frame: Time from registration to the earliest date documentation of disease progression or death due to any cause, assessed up to 1 year
Response evaluated according to positron emission tomography/computed tomography-based response criteria
The number of patients who achieve a complete metabolic response or partial metabolic response will be assessed.
Time frame: Up to 1 year
Survival time
The distribution of survival time will be estimated using the method of Kaplan-Meier.
Time frame: Time from registration to death due to any cause, assessed up to 1 year
Toxicity profile defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment evaluated via Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Overall toxicity incidence as well as toxicity profiles by dose level and patient will be explored and summarized.
Time frame: Up to 1 year
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