A PHASE IB/II STUDY TO EVALUATE THE SAFETY AND EFFICACY OF VISMODEGIB IN RELAPSED/REFRACTORY ACUTE MYELOGENOUS LEUKEMIA (AML) AND RELAPSED/REFRACTORY HIGH-RISK MYELODYSPLASTIC SYNDROME (MDS)
Inclusion Criteria:
- Adult patients, >/= 18 years of age
- Patients with documented relapsed or refractory AML, except acute promyelocytic
leukemia (APL [M3 subtype]), or relapsed or refractory high-risk MDS (high-risk MDS
defined as International Prognostic Scoring System (IPSS) Int-2 or high and >/= 10%
blasts in bone marrow)
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- Negative serum pregnancy test for women of childbearing potential and use of two
forms of contraception while enrolled in the study and for 7 months after the patient
discontinues from study
- Male patients with female partners of childbearing potential must agree to use a
latex condom and to advise their female partner to use an additional method of
contraception during the study and for 2 months after the last dose of vismodegib
- All non-hematological adverse events of any prior chemotherapy, surgery, or
radiotherapy must have resolved to NCI CTCAE Grade = 2 prior to starting therapy
- Adequate hepatic and renal function
Exclusion Criteria:
- Prior treatment with a Hh pathway inhibitor
- Prior therapy for the treatment of malignancy within 14 days of Day 1, with the
exception of:
Hydroxyurea in patients who need to continue this agent to maintain WBC counts =
50,000/mL. Hydroxyurea must be discontinued by Day 14 of the study
- Current evidence of active CNS leukemia
- Any other active malignancy (except non-melanoma skin cancer or carcinoma in situ of
the cervix)
- Any severe and/or uncontrolled medical conditions or other conditions that could
affect their participation in the study such as:
Unstable angina, symptomatic or otherwise uncontrolled arrhythmia requiring medication
(does not include stable, lone atrial fibrillation), or myocardial infarction = 6 months
before study treatment start Any active (acute or chronic) or uncontrolled
infection/disorders that impair the ability to evaluate the patient or for the patient to
complete the study
- Pregnant or breast-feeding women
- Patients who refuse to potentially receive blood products and/or have a severe
hypersensitivity to blood products