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

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of everolimus when administered in
combination with bendamustine (bendamustine hydrochloride) in defined hematologic
malignancies.

II. To determine the safety and tolerability of administering everolimus in combination with
bendamustine chemotherapy.

SECONDARY OBJECTIVES:

I. To determine the efficacy of everolimus when administered in combination with bendamustine
in adult patients with relapsed/refractory hematological malignancies.

OUTLINE: This is a dose-escalation study of everolimus.

Patients receive bendamustine hydrochloride intravenously (IV) over 30 minutes on days 1 and
2 and everolimus orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in
the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Inclusion Criteria:

- Measurable disease

- 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

- All the patients need to have biopsy proven active disease at the time of clinical
trial

- Eastern Cooperative Oncology Group performance status of =< 2 study entry

- Absolute neutrophil count >= 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 < 2

Exclusion Criteria:

- Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent form

- Currently part of or have participated in any clinical investigation with an
investigational drug within 1 month prior to dosing

- Any severe and/or uncontrolled medical conditions

- Uncontrolled diabetes mellitus

- Known impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of oral everolimus

- Currently receiving anticancer therapies or who have received anticancer therapies
within 2 weeks of the start of everolimus

- Known hypersensitivity to everolimus or bendamustine

- Known central nervous system (CNS) disease (NHL, diffuse large B cell lymphoma
[DLBCL])

- Recent major surgery within 14 days prior to cycle 1, day 1

- Taking strong cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors

- Received live attenuated 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

- History of another primary malignancy

- 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

- 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) or have had surgical bilateral
oophorectomy (with or without 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