A Phase I Trial of Carfilzomib in Adult Patients With Relapsed Acute Myeloid and Acute Lymphoblastic Leukemia

Inclusion Criteria:

Disease Related

- Relapsed acute myeloid leukemia or relapsed acute lymphoblastic leukemia. Patients
with primary refractory AML or ALL (after standard induction chemotherapy) are also
eligible if they have evidence of persistent disease documented by bone marrow biopsy
done within 14 days of trial entry.

- Subjects must have disease documented on bone marrow biopsy done within 14 days of
starting cycle 1

Demographic

- Males and females ≥ 18 years old.

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

Laboratory

- Peripheral blast count must be ≤ 30,000 on the first day of study drug
administration. Leukopheresis and hydrea are acceptable measures of leuko-reduction
prior to beginning the study drug.

- Adequate hepatic function with ALT/SGPT ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0
x ULN if the transaminase elevation is due to leukemic involvement. Serum bilirubin
≤ 2.0 x ULN.

- Adequate renal function with calculated creatinine clearance of ≥ 15 mL/min
(calculated using the Cockcroft and Gault formula) or measured creatinine clearance ≥
15 mL/min from 24 hour urine collection.

- Uric acid, if elevated, must be corrected to within laboratory normal range prior to
dosing.

Ethical / Other

- Ability to provide written informed consent obtained prior to participation in the
study and any related procedures being performed.

- Women of childbearing age must have a negative serum pregnancy test within 7 days
prior to initiating therapy and be willing to not become pregnant to by using
effective contraception while undergoing treatment and for at least 3 months
afterwards.

- Men must be willing not to father a new child while receiving therapy. They must use
an effective barrier method of contraception during the study and for 3 months
following the last dose.

Exclusion Criteria:

Subjects meeting any of the following exclusion criteria are not eligible to enroll in
this study.

Disease Related

- Active CNS leukemia.

- Receiving any other investigational agents within 14 days of first dose of study
drug.

- Had cytotoxic chemotherapy within 14 days of first dose of study drug. Leukopheresis
and hydrea are allowed as specified per protocol

- Had allogeneic stem cell transplantation within 100 days of first dose of study drug.
Patients with a history of graft-versus-host disease on a stable dose of
immunosuppression and who are otherwise medically fit are eligible for the trial.
Patients with active graft-versus host disease are excluded.

- Had radiotherapy within 14 days prior to study enrollment.

- Subjects with pleural effusions requiring thoracentesis or ascites requiring
paracentesis.

Concurrent Conditions

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, congestive heart failure of NYHA class 3 or 4, unstable angina pectoris,
cardiac arrhythmia, or psychiatric illness/social situation that would limit
compliance with study requirements.

- Major surgery within three weeks before Day 1.

- Active hepatitis A, B, C infection.

- Known or suspected HIV infection or subjects who are HIV seropositive.

- Significant neuropathy (Grade 3, 4) at the time of study initiation.

- Patients in whom oral and/or IV fluid hydration is contraindicated, e.g., due to
pre-existing pulmonary, cardiac, or renal impairment, will not be eligible to
participate in the clinical trial.

Ethical / Other

-Female subjects who are pregnant or lactating.