Phase 1b/2, Multicenter, Open-label Study of the Safety and Activity of Oprozomib in Patients With Hematologic Malignancies

Inclusion Criteria

INCLUSION CRITERIA:

Phase 1b

- Histologically confirmed diagnosis of a hematologic malignancy, excluding patients
with acute leukemia or MDS.

- Relapsed after standard therapy for their malignancy and considered to be an
appropriate candidate for a Phase 1 clinical study by their treating physician.

Phase 2

- Multiple myeloma with measurable disease

- Waldenström macroglobulinemia with symptomatic relapse

- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.

Ethical/Other

- Patients must sign a written informed consent form in accordance with federal, local,
and institutional guidelines.

- Female patients of childbearing potential must have a negative serum or urine
pregnancy test and agree to use effective contraception. Male patients must use an
effective barrier method of contraception.

EXCLUSION CRITERIA:

- Chemotherapy with approved or investigational anticancer therapeutics, including
steroid therapy intended to treat underlying malignancy, within 3 weeks prior to
first dose or 6 weeks for antibody therapy.

- Radiation therapy within 3 weeks prior to first dose. Radioimmunotherapy within 8
weeks prior to first dose. Localized radiation therapy within 1 week prior to first
dose.

- Immunotherapy within 3 weeks prior to first dose (except for antibody therapy, where
6 weeks is required).

- Prior stem cell transplant (SCT) therapy (autologous SCT within the prior 8 weeks;
allogeneic SCT within the prior 16 weeks). Patients with prior allogeneic SCT should
not have evidence of moderate-to-severe graft-vs-host disease (GvHD; as defined in
Filipovich 2005).

- Evidence of central nervous system (CNS) lymphoma.

- Prior treatment with carfilzomib.

- Major surgery within 3 weeks prior to first dose.

- Symptomatic Congestive heart failure, ischemia, conduction abnormalities, or
myocardial infarction within 6 months.

- Acute active infection requiring systemic antibiotics, antivirals, or antifungals.

- Known or suspected human immunodeficiency virus (HIV) infection or patients who are
HIV seropositive.

- Active hepatitis A, B, or C infection.

- Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the
first dose.

- Patients with pleural effusions requiring routine thoracentesis or ascites requiring
routine paracentesis.

- Female patients who are pregnant or lactating.