Vincristine Sulfate Liposome Injection (Marqibo®), Bendamustine and Rituximab—Phase I Trial in Indolent B-cell Lymphoma

Bendamustine-rituximab is a standard chemotherapy regimen for treatment of many indolent
B-cell lymphomas, but most patients experience a recurrence of the lymphoma. Vincristine
sulfate has been a traditional component of chemotherapy regimens in non-Hodgkin lymphoma and
it is possible that adding it to the bendamustine-rituximab regimen might provide a better
quality of remissions or longer duration of remissions with acceptable toxicity.

This is a phase 1, single-center, open-label, single-arm trial in patients with indolent
B-cell non-Hodgkin lymphoma otherwise appropriate for bendamustine-rituximab as initial or
subsequent line of therapy. Patients will receive the of rituximab and bendamustine in
combination with escalating doses of vincristine sulfate liposome injection (Marqibo®). The
objective of this study is to assess safety of this combination by establishing the maximum
tolerated dose of vincristine sulfate liposome injection (Marqibo®) in the combination.

Inclusion Criteria:

- Histologically confirmed indolent B-cell non-Hodgkin lymphoma.

- Radiological measurable disease.

- Previous treatment for lymphoma is allowed, with the exception of use of bendamustine
within 6 months or any prior use of vincristine sulfate liposome injection

- Eastern Cooperative Oncology Group performance status 0 or 1;

- Life expectancy of at least 6 months;

- Adequate organ and marrow function;

- Women of child-bearing potential and men must agree to use adequate contraception.

- Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

- History of allergic reactions attributed to any drug used in the study.

- Any lymphoma-directed therapy within 4 weeks.

- Any prior treatment with vincristine sulfate liposome injection.

- Prior treatment with bendamustine or vincristine sulfate within 180 days of
enrollment.

- Patients who are receiving any other investigational agents with the exception of
endocrine therapy for breast or prostate cancer.

- Central nervous system involvement.

- Peripheral sensory or motor neuropathy.

- History of a demyelinating condition.

- Positive test for the Human Anti-Chimeric Antibody (HACA).

- Patients receiving any medications or substances that are strong inhibitors or
inducers of Cytochrome P450, family 3, subfamily A (CYP3A) enzyme are ineligible.

- Uncontrolled intercurrent illness.

- Prisoners.

- Pregnant or breast-feeding women.

- Known Human Immunodeficiency Virus (HIV) or active Hepatitis B infection

- Any prior or active cancer, which in the opinion of the investigator would preclude
safe participation in this study.