Nab-paclitaxel/Rituximab-coated Nanoparticle AR160 in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

PRIMARY OBJECTIVES:

I. To establish the maximum tolerated dose (MTD) of nab-paclitaxel/rituximab-coated
nanoparticle AR160 (AR160) in patients with relapsed/refractory B-cell non-Hodgkin lymphoma
(NHL). (Phase I)

SECONDARY OBJECTIVES:

I. To assess the toxicity and safety of AR160. II. To assess complete response rate (CR)
progression free survival (PFS), and overall survival (OS) of AR160 with relapsed/refractory
B-cell NHL.

TERTIARY OBJECTIVES:

I. Evaluate pharmacokinetics (PK) of AR160 in two formal PK studies, dose 1 of cycle 1 (48
hours [h] PK analysis) and dose 1 of cycle 2 (24h PK analysis).

OUTLINE: This is a dose-escalation study.

Patients receive nab-paclitaxel/rituximab-coated nanoparticle AR160 intravenously (IV) over
30-60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for up to 5
years.

Inclusion Criteria:

- Histological confirmation of relapsed/refractory B-cell NHL, CD20+

- NOTE: patients with small lymphocytic lymphoma (SLL) are eligible however
patients with chronic lymphocytic leukemia (CLL) are not eligible

- Waldenstrom macroglobulinemia patients are not eligible; aggressive lymphoma
patients who are transplant eligible must have undergone a transplant

- The biopsy confirming relapse can be up to 24 weeks prior to registration as long
as there is no intervening therapy

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

- Absolute neutrophil count (ANC) >= 1500/mm^3

- Platelet count >= 75,000/mm^3

- Hemoglobin >= 8.0 g/dL

- Total bilirubin =< 1.5 X upper limit of normal (ULN) or if total bilirubin is > 1.5 X
ULN, the direct bilirubin =< ULN

- Alkaline phosphatase =< 3 X ULN unless due to direct lymphoma involvement, and then =<
5 X ULN

- Aspartate transaminase (AST) =< 3 X ULN unless due to direct lymphoma involvement, and
then =< 5 X ULN

- Calculated creatinine clearance must be >= 30 ml/min using the Cockcroft-Gault formula

- Life expectancy >= 3 months

- Ability to provide written informed consent

- Willing to return to enrolling institution for follow-up (during the treatment and
observation phases of the study)

- Willing to provide tissue for central review blood samples for correlative research
purposes

- No other therapy with demonstrated clinical benefit in relapsed/refractory B-cell NHL
available to the patient

- Negative pregnancy test done =< 7 days prior to registration, for women of
childbearing potential only

Exclusion Criteria:

- Any of the following:

- Pregnant women

- Nursing women

- Men or women of childbearing potential who are unwilling to employ adequate
contraception

- Active central nervous system (CNS) lymphoma or cerebrospinal fluid involvement with
malignant lymphoma cells that requires therapy

- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
of the investigator, would make the patient inappropriate for entry into this study or
interfere significantly with the proper assessment of safety and toxicity of the
prescribed regimens

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Patients who received most recent therapy =< 4 weeks prior to registration; NOTE: use
of systemic steroid therapy is allowed pretreatment

- Receiving any other investigational agent which would be considered as a treatment for
the primary neoplasm

- Patients must be disease-free of prior invasive malignancies for > 5 years prior to
registration with the exception of curatively-treated basal cell or squamous cell
carcinoma of the skin or carcinoma in situ of the cervix

- Patients with >= 25% of the bone marrow radiated for other diseases

- Other medical conditions including but not limited to:

- History of liver disease such as cirrhosis, chronic active hepatitis, chronic
persistent hepatitis or hepatitis B or C

- Active infection requiring parenteral antibiotics

- New York Heart Association class II-IV congestive heart failure (serious cardiac
arrhythmia requiring medication)

- Myocardial infarction or unstable angina =< 6 months prior to registration

- Congestive heart failure requiring use of ongoing maintenance therapy for
life-threatening ventricular arrhythmias

- Clinically significant peripheral vascular disease

- History of CNS disease (e.g., primary brain tumor, vascular abnormalities, etc.),
clinically significant stroke or transient ischemic attack (TIA) =< 6 months
prior to registration, seizures not controlled with standard medical therapy

- Neuropathy ˃ grade 3

- Administration of strong CYP2C8 or CYP3A4 inhibitors or inducers =< 10 days prior to
registration