Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Neoplasms by Histologic Type

Hematologic Diseases

Bone Marrow Diseases

Precancerous Conditions

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Cytarabine

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

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

cytarabine

vismodegib

Clinical Trials

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.

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

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)

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.

CR was defined as achieved if the neutrophils count \>1000 cells/µL, platelets count \>100000/µL, bone marrow blasts \<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 EMD. CRi was defined if either of the cell (neutrophil or platelet) lineage was not recovered (neutrophils \> 1000 cells/µL or 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. The 95% confidence intervals (CI) were constructed using Blyth-Still-Cassella method.

DOR is defined as the time from the first occurrence of a documented overall response to the time of relapse, as determined by the investigator using International Working Group (IWG) criteria (Participants not falling under any of the response criteria \[CR or CRi or MLFS or PR\] described under outcome measure 1 were considered as non-responders) or death from any cause during the study (defined as death within 30 days after the last dose of study drug).

OS was defined as the time from start of study drug to death from any cause. OS was estimated using Kaplan-Meier analysis. Participants alive at the last date known to be alive were censored for the analysis.

PK data was planned to be reported only if the results of Cohort 2 are available.

Hoffmann-La Roche

Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'poor risk cytogenetics' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.

Poor Risk Cytogenetics

Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'FLT-3 mutation positive' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.

FLT-3 Mutation Positive

Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling neither under 'poor risk cytogenetics' nor 'FLT-3 mutation positive' subgroup were included in this group and received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.

Neither Poor Risk Cytogenetics Nor FLT-3

Total

Age, Continuous

Sex: Female, Male

Included all enrolled participants who received at least 1 dose of study drug.

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

Medical Communications

Neither Poor Risk Cytogenetics Nor FLT3

As the primary efficacy time-point (Week 8) was not reached for all participants due to study termination based on interim data analysis, the analysis of this outcome measure could not be performed, as per planned analysis.

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

MLFS

Efficacy analysis population included all enrolled participants. Here "number of participants analyzed" included participants who were evaluable for tumor response at anytime during the study.

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

DOR of participants with CRi (n=0,0,1)

DOR of participants with PR (n=0,0,1)

Efficacy population including participants who were considered as responders.

Duration of Overall Response (DOR)

Median Overall Survival (OS) Time

Percentage of Participants With an Event of Death During the Study

As the study was terminated prior to Cohort 2 enrollment, PK analysis could not be performed, as planned.

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

Participants in Cohort 2 were planned to receive low-dose subcutaneous injections of cytarabine in combination with continuous daily vismodegib (150 mg orally).

Planned Cohort 2

No participants were enrolled as the study was terminated prior to the initiation of Cohort 2.

Area Under the Concentration-time Curve (AUC) of Cytarabine

Participants with relapsed/refractory acute myeloid leukemia (AML) or relapsed/refractory high-risk myelodysplastic syndrome (MDS) falling under 'poor risk cytogenetics' subgroup received oral 150 milligrams (mg) dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.

Spots Global Cancer Trial Database for A Study of Vismodegib in Patients With Relapsed/Refractory Acute Myelogenous Leukemia and Relapsed Refractory High-Risk Myelodysplastic Syndrome

Trial Identification

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Study Description

Keywords

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