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

NCT01880437 | Terminated Phase 2 Results

• 2 other identifiers: GO288522013-001570-14
• Study Type: interventional
• Target: 38
• Locations: 3 countries
• Sites: 14

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.

Conditions

Myelodysplastic Syndromes, Myelogenous Leukemia, Acute

Outcome Measures

Primary Outcomes (1)

• 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

  CR was defined as achieved if the neutrophils count was greater than (\>) 1000 cells per microliter (µL), platelets count \>100000/µL, bone marrow blasts percentage (%) less than (\<) 5, no Auer rods (clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of leukemic blasts), no transfusion requirements and no signs of extra medullary disease (EMD). CRi was defined if either of the cell (neutrophil or platelet) lineage was not recovered (neutrophils \>1000 cells/µL or Not applicable \[NA\] or platelets count \>100000/µL or NA), bone marrow blasts \<5% with no Auer rods and confirmed by flow cytometry with no signs of EMD. MLFS (neutrophil and platelet criteria were NA) was defined as bone marrow blasts \<5% with no Auer rods and confirmed by flow cytometry with no signs of EMD. PR was defined as neutrophils count \>1000 cells/µL, platelets count \>100000/µL, and \>50% decrease from baseline to a range of 5-25% of bone marrow blasts or blasts \<5% with Auer rods.

  Week 8

Secondary Outcomes (6)

• Percentage of Participants With CR, CRi, MLFS or PR at Anytime During Study Treatment

  Up to 30 days of last dose of study drug (maximum treatment duration = 225 days)

• Duration of Overall Response (DOR)

  Up to 30 days of last dose of study drug (maximum treatment duration = 225 days)

• Median Overall Survival (OS) Time

  Up to death or 30 days of last dose of study drug (maximum treatment duration = 225 days)

• Percentage of Participants With an Event of Death During the Study

  Up to death or 30 days of last dose of study drug (maximum treatment duration = 225 days)

• Pharmacokinetics (PK): Steady-state Plasma Concentration of Vismodegib

  Predose on Days 8, 29 and 57

Study Arms (1)

Vismodegib

EXPERIMENTAL

Drug: cytarabine; Drug: vismodegib

Interventions

cytarabine DRUG

Cohort 2: 20 mg sc daily for 10 days starting Day 1, with a possible further cycle of 20 mg sc daily for 5 days starting no earlier than Day 29

Vismodegib

vismodegib DRUG

Cohorts 1 and 2: 150 mg orally daily

Also known as: RO5450815

Vismodegib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (14)

Unknown Facility

Stanford, California, 94305, United States

Location

Unknown Facility

Ann Arbor, Michigan, 48109, United States

Location

Unknown Facility

Kansas City, Missouri, 64131, United States

Location

Unknown Facility

New York, New York, 10065, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

Edmonton, Alberta, T6L5X8, Canada

Location

Unknown Facility

Toronto, Ontario, M5G 2M9, Canada

Location

Unknown Facility

Montreal, Quebec, H1T 2M4, Canada

Location

Unknown Facility

Montreal, Quebec, H3T 1E2, Canada

Location

Unknown Facility

Braunschweig, 38114, Germany

Location

Unknown Facility

Essen, 45122, Germany

Location

Unknown Facility

Hamburg, 20246, Germany

Location

Unknown Facility

Heidelberg, 69120, Germany

Location

Unknown Facility

Münster, 48149, Germany

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid

Interventions

Cytarabine; HhAntag691

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

This study was prematurely terminated because of lower-than-expected efficacy observed in interim data analyses.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-LaRoche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2013
• First Posted: June 19, 2013
• Study Start: September 1, 2013
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: December 15, 2015
• Results First Posted: December 15, 2015

Record last verified: 2015-11

Locations

DE (5); US (5); CA (4)