Phase 1 Study of Everolimus in Combination With Brentuximab Vedotin in Patients With Relapsed or Refractory Hodgkin Lymphoma
Phase 1 Study of Everolimus in Combination With Brentuximab Vedotin in Patients With Relapsed or Refractory Hodgkin Lymphoma
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.
Inclusion Criteria:
Exclusion Criteria:
Any of the following
Candidate for known standard therapy for the patient's disease that is potentially curative
Therapy with myelosuppressive chemotherapy or biologic therapy < 21 days prior to registration unless the patient has recovered from the nadir of the previous treatment to a level that meets the inclusion eligibility criteria of this protocol
Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) =< 5 effective half-lives prior to registration or who have not recovered from side effects of such therapy
Received wide field radiotherapy =< 28 days or limited field radiation for palliation =< 14 days prior to registration or who have not recovered from side effects of such therapy
Receiving corticosteroids > 20 mg of prednisone per day (or equivalent); Note: the dose should be noted on the medication record each cycle
Persistent toxicities >= grade 2 from prior chemotherapy or biological therapy regardless of interval since last treatment
Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)
Known positivity for human immunodeficiency virus (HIV); Note: baseline testing for HIV is not required
Active hepatitis B or C with uncontrolled disease
Other active malignancy requiring treatment that would interfere with the assessments of response of the lymphoma to protocol treatment
Inability to swallow or impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) that would preclude use of oral medications
Major surgery =< 14 days prior to registration or have not recovered from side effects of such therapy
Treated with any hematopoietic colony-stimulating growth factors (e.g., granulocyte-colony stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF]) =< 2 weeks prior to study registration; NOTE: erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to study registration, may be continued
Pre-existing neuropathy of >= grade 2
Patients receiving strong inhibitors of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4)
Use of the following strong or moderate inhibitors are prohibited =< 7 days prior to registration
Use of the following inducers are prohibited =< 12 days prior to registration