Everolimus and Bendamustine Hydrochloride in Treating Patients with Relapsed or Refractory Hematologic Cancer

Inclusion Criteria

• Measurable disease (at least one lesion that is 1.5 cm in the longest diameter on cross‐sectional imaging and measurable in 2 perpendicular dimensions per computed tomography [CT]) for non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL) subjects; for myeloma patients measurable disease is defined as presence of more than 5% plasma cells in the bone marrow aspiration and/or presence of monoclonal gammopathy in serum protein electrophoresis (SPEP) and immunofixation
• Baseline hemoglobin level of > 7.0 g/dl
• Understand and voluntarily sign an informed consent form
• Able to adhere to the study visit schedule and other protocol requirements
• Disease status: all the patients need to have scan or biopsy proven active disease at the time of clinical trial * Multiple myeloma: patient must have failed at least one line of therapy * Chronic lymphocytic leukemia (CLL): status post (S/P) at least one line of therapy * Hodgkin’s lymphoma: S/P at least two lines of therapy * Follicular lymphoma: S/P at least one line of therapy * Mantle cell lymphoma: S/P at least one line of therapy * Diffuse large B cell lymphoma: S/P at least two lines of therapy
• Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 study entry
• Absolute neutrophil count (ANC) >= 1,000/mm^3
• Platelet count >= 50,000/mm^3
• Calculated creatinine clearance > 40 ml/min or 24 hour urine
• Total bilirubin =< 2 x upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x upper limit of normal
• International normalized ratio (INR) < 2

Exclusion Criteria

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
• Patients who are currently part of or have participated in any clinical investigation with an investigational drug within 1 month prior to dosing
• Patients who have any severe and/or uncontrolled medical conditions such as: * Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months prior to start of everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease * Symptomatic congestive heart failure of New York heart Association class III or IV * Active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis or decompensated liver disease, and chronic hepatitis * Known severely impaired lung function (spirometry and diffusion capacity of carbon monoxide [DLCO] 50% or less of normal and oxygen [O2] saturation 88% or less at rest on room air) * Active, bleeding diathesis
• Uncontrolled diabetes mellitus as defined by hemoglobin A1c (HbA1c) > 8% despite adequate therapy; patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and anti-diabetic treatment must be monitored closely throughout the trial and adjusted as necessary
• Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
• Patients currently receiving anticancer therapies or who have received anticancer therapies within 2 weeks of the start of everolimus (including chemotherapy, radiation therapy, antibody based therapy)
• Known hypersensitivity to everolimus or bendamustine
• Known central nervous system (CNS) disease (NHL, diffuse large B cell lymphoma [DLBCL])
• Patients with recent major surgery within 14 days prior to cycle 1, day 1
• Patients who are taking strong cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors
• Patients who have received live attenuated vaccines within 1 week of start of everolimus and during the study; patient should also avoid close contact with others who have received live attenuated vaccines; examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG (bacillus Calmette-Guerin), yellow fever, varicella and TY21a typhoid vaccines
• Known sero-positive for active or past viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); patients who are sero-positive because of hepatitis B virus vaccine are eligible
• Patients who have a history of another primary malignancy from which the patient has been disease free for < 1 year; with the exceptions of non-melanoma skin cancer and carcinoma in situ of the cervix, uteri, or breast
• Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study
• Pregnant or nursing (lactating) women
• Women of childbearing potential (WOCBP) (including female pediatric patients who are menarcheal or who become menarcheal during the treatment), defined as all women physiologically capable of becoming pregnant, must use highly effective methods of contraception during the study and 8 weeks after; women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms); highly effective methods of birth control have less than 1% chance of unwanted pregnancy during one year, if used appropriately according to the instruction of the manufacturer; highly effective contraception methods include combination of any two of the following: * Use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); or other forms of hormonal contraception that have comparable efficacy; in case of use of oral contraception women should have been stable on the oral agent for a minimum of 3 months before taking everolimus * Total abstinence or; male partner sterilization; (the vasectomized male partner should be the sole partner for that subject) * Female sterilization; have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks prior to randomization; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential
• Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment