Phase 1 Study of Everolimus in Combination With Brentuximab Vedotin in Patients With Relapsed or Refractory Hodgkin Lymphoma
Overview
- Phase
- Phase 1
- Intervention
- Brentuximab Vedotin
- Conditions
- Recurrent Hodgkin Lymphoma
- Sponsor
- Mayo Clinic
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Maximum tolerated dose (MTD) of everolimus in combination with brentuximab vedotin, graded by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
- Status
- Terminated
- Last Updated
- 6 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Biopsy-proven relapsed (response to last treatment \> 6 months duration), refractory (no response to last treatment or response duration \< 6 months) or residual Hodgkin lymphoma; NOTE: re-biopsy is necessary unless the patient has had a previous biopsy \< 180 days prior to registration on this protocol with no intervening therapy and tissue is available for translational research studies
- •Eligible to receive standard brentuximab vedotin for relapsed Hodgkin lymphoma
- •Measurable disease by CT or magnetic resonance imaging (MRI) or the CT portion of the PET/CT: must have at least one lesion that has a single diameter of \>= 2 cm
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
- •Absolute neutrophil count (ANC) \>= 1000/uL
- •Hemoglobin (Hgb) \>= 9 g/dl
- •Platelet (PLT) \>= 75,000/uL
- •Serum total bilirubin within normal range (or =\< 1.5 x upper limit of normal \[ULN\] if liver metastases are present; or total bilirubin =\< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert syndrome)
- •Aspartate aminotransferase (AST) =\< 1.5 x ULN
- •Alkaline phosphatase =\< 1.5 x ULN
Exclusion Criteria
- •Any of the following
- •Pregnant women
- •Nursing women
- •Women of childbearing potential who are unwilling to employ highly effective contraception while on study treatment and for 6 months after the final dose of treatment; NOTE: women of childbearing potential are defined as all women physiologically capable of becoming pregnant
- •Men of childbearing potential who are unwilling to employ highly effective contraception while on study treatment and for 6 months after the final dose of treatment and should not father a child during this time; NOTE: men of childbearing potential are defined as all males physiologically capable of conceiving offspring
- •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
Arms & Interventions
Treatment (everolimus, brentuximab vedotin)
Patients receive brentuximab vedotin IV over 30 minutes on day 1 and everolimus PO QD or 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.
Intervention: Brentuximab Vedotin
Treatment (everolimus, brentuximab vedotin)
Patients receive brentuximab vedotin IV over 30 minutes on day 1 and everolimus PO QD or 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.
Intervention: Everolimus
Treatment (everolimus, brentuximab vedotin)
Patients receive brentuximab vedotin IV over 30 minutes on day 1 and everolimus PO QD or 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.
Intervention: Laboratory Biomarker Analysis
Treatment (everolimus, brentuximab vedotin)
Patients receive brentuximab vedotin IV over 30 minutes on day 1 and everolimus PO QD or 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.
Intervention: Pharmacological Study
Outcomes
Primary Outcomes
Maximum tolerated dose (MTD) of everolimus in combination with brentuximab vedotin, graded by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time Frame: 21 days
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).
Secondary Outcomes
- Complete response (CR) rate(Up to 1 year)
- Overall response rate (ORR) (complete response [CR] or partial response [PR])(Up to 1 year)
- Duration of response(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)
- Progression-free survival(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(Up to 1 year)
- Survival time(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(Up to 1 year)