A Study of Vismodegib in Patients With Relapsed/Refractory Acute Myelogenous Leukemia and Relapsed Refractory High-Risk Myelodysplastic Syndrome

Roche

Status and phase

Terminated

Phase 2

Conditions

Myelodysplastic Syndromes, Myelogenous Leukemia, Acute

Treatments

Drug: vismodegib

Drug: cytarabine

Study type

Interventional

Funder types

Industry

Identifiers

NCT01880437

GO28852

2013-001570-14 (EudraCT Number)

Details and patient eligibility

About

This study will assess the safety and efficacy of vismodegib in patients with relapsed/refractory acute myelogenous leukemia (AML) and relapsed/refractory high-risk myelodysplastic syndrome (MDS). Patients in Cohort 1 will receive single-agent vismodegib 150 mg orally daily. In Cohort 2, patients will receive vismodegib 150 mg orally daily in combination with cytarabine 20 mg subcutaneously for 10 days.

Anticipated time on study treatment is until disease progression, intolerable toxicity, or patient withdrawal of consent.

Enrollment

38 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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 National Cancer Institute Common Terminology Criteria for Adverse Events (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 white blood cell (WBC) counts </= 50,000/mL. Hydroxyurea must be discontinued by Day 14 of the study

Current evidence of active central nervous system (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