Sorafenib and Everolimus in Treating Patients With Relapsed or Refractory Lymphoma or Multiple Myeloma

• Status: Completed
• Trial end date: 2019-08-08
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Sorafenib and everolimus may stop the growth of cancer cells by blocking blood flow to the cancer and by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I/II trial is studying the side effects and best dose of sorafenib and everolimus and to see how well they work in treating patients with relapsed or refractory non-Hodgkin's lymphoma, Hodgkin's lymphoma, or multiple myeloma.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mayo Clinic
• Collaborator: University of Iowa
• Treatments: Everolimus; Niacinamide; Sirolimus; Sorafenib

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed diagnosis of 1 of the following:

• Multiple myeloma

• Non-Hodgkin's lymphoma

• Hodgkin's lymphoma

• Relapsed or refractory disease

• Measurable disease, as defined according to diagnosis as follows:

• Multiple myeloma, meeting 1 of the following criteria:

• Serum monoclonal protein ≥ 1.0 g/dL

• Urine monoclonal protein ≥ 200 mg by 24-hour electrophoresis

• Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio

• Monoclonal bone marrow plasmacytosis ≥ 30% (evaluable disease)

• Lymphoma, meeting 1 of the following criteria:

• Measurable disease by CT scan or MRI or PET/CT scan, defined as ≥ 1 lesion that has a single diameter of ≥ 2 cm OR tumor cells in the blood ≥ 5 x10^9/L

• Skin lesions can be used if the area is ≥ 2 cm in ≥ 1 diameter and photographed with a ruler

• Lymphoplasmacytic lymphoma without measurable lymphadenopathy, meeting both of the following criteria:

• Bone marrow lymphoplasmacytosis with > 10% lymphoplasmacytic cells or aggregates, sheets, lymphocytes, plasma cells, or lymphoplasmacytic cells on bone marrow biopsy

• Quantitative IgM monoclonal protein > 1,000 mg/dL

• Not a candidate for known standard potentially curative therapy

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Life expectancy ≥ 12 weeks

• ANC ≥ 1,500/mm³

• Hemoglobin ≥ 9 g/dL

• Platelet count ≥ 75,000/mm³

• Bilirubin ≤ 1.5 times upper limit of normal (ULN) OR direct bilirubin normal

• AST ≤ 3 times ULN (5 times ULN if liver involvement)

• Creatinine ≤ 2.5 times ULN

• INR < 1.5 or activated PTT < 1.5 times ULN (no concurrent anticoagulants)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective barrier contraception during and for at least 2 weeks after completion of study treatment

• No uncontrolled infection

• No NYHA class III-IV congestive heart failure

• No unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months)

• No myocardial infarction within the past 6 months

• No uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg or diastolic BP > 90 mm Hg, despite optimal medical management

• No known HIV positivity

• No other active malignancy requiring treatment

• No inability to swallow

• No gastrointestinal (GI) function impairment or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, or diarrhea, malabsorption syndrome, or small bowel resection) or preclude use of oral medications

• No thrombolic or embolic events (e.g., cerebrovascular accident, including transient ischemic attacks) within the past 6 months

• No pulmonary hemorrhage or bleeding event ≥ grade 3 within the past 4 weeks

• No severe or uncontrolled medical conditions or other conditions that would preclude study compliance

• No liver disease, such as cirrhosis, chronic hepatitis or chronic persistent hepatitis, or uncontrolled infections

• No serious nonhealing wound, ulcer, or bone fracture

• No evidence or history of serious bleeding diathesis or coagulopathy, such as hemophilia or von Willebrand's disease

• No significant traumatic injury within the past 4 weeks

• No known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus)

PRIOR CONCURRENT THERAPY:

• More than 3 weeks since prior myelosuppressive chemotherapy or biological therapy and recovered

• More than 4 weeks since prior major surgery or open biopsy

• Lymph node biopsy within past 4 weeks allowed

• Prior everolimus allowed

• No concurrent immunosuppressant therapy

• Concurrent stable chronic doses of steroids (≤ 20 mg of prednisone per day) for disorders other than lymphoma (i.e., rheumatoid arthritis, polymyalgia rheumatica, adrenal insufficiency, asthma) or for pruritus or fever associated with lymphoma allowed

• Concurrent corticosteroids at the lowest possible dose necessary to control symptoms in patients with CNS lymphoma allowed

• No concurrent CYP450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital), rifampin, or Hypericum perforatum (St. John's wort)

• No other concurrent immunotherapy, radiotherapy, or chemotherapy

• No concurrent chronic oxygen therapy

• No concurrent warfarin or heparin

• No other concurrent investigational therapy