Clinical trial NCT01880437: A Study of Vismodegib in Patients With Relapsed/Refractory Acute Myelogenous Leukemia and Relapsed Refractory High-Risk Myelodysplastic Syndrome
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Myelodysplastic Syndromes, Myelogenous Leukemia, Acute
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-06-19
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

* Pregnant or breast-feeding women
* Patients who refuse to potentially receive blood products and/or have a severe hypersensitivity to blood products

Primary outcomes:
measure: Percentage of Participants With a Complete Response (CR) or CR With Incomplete Blood Count Recovery (CRi) or Morphologic Leukemia Free State (MLFS) or Partial Response (PR) at Week 8
timeFrame: Week 8
Secondary outcomes:
measure: Percentage of Participants With CR, CRi, MLFS or PR at Anytime During Study Treatment
timeFrame: Up to 30 days of last dose of study drug (maximum treatment duration = 225 days)
measure: Duration of Overall Response (DOR)
timeFrame: Up to 30 days of last dose of study drug (maximum treatment duration = 225 days)
measure: Median Overall Survival (OS) Time
timeFrame: Up to death or 30 days of last dose of study drug (maximum treatment duration = 225 days)
measure: Percentage of Participants With an Event of Death During the Study
timeFrame: Up to death or 30 days of last dose of study drug (maximum treatment duration = 225 days)
measure: Pharmacokinetics (PK): Steady-state Plasma Concentration of Vismodegib
timeFrame: Predose on Days 8, 29 and 57
measure: Area Under the Concentration-time Curve (AUC) of Cytarabine
timeFrame: Predose, 0.25, 0.5, 1, 3, 6 hours post-dose on Days 1, 8 and 29
Other outcomes:
Locations:
city: Stanford
country: United States
state: California
city: Ann Arbor
country: United States
state: Michigan
city: Kansas City
country: United States
state: Missouri
city: New York
country: United States
state: New York
city: Houston
country: United States
state: Texas
city: Edmonton
country: Canada
state: Alberta
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Braunschweig
country: Germany
city: Essen
country: Germany
city: Hamburg
country: Germany
city: Heidelberg
country: Germany
city: Münster
country: Germany
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: