Myelodysplastic Syndromes, Myelogenous Leukemia, AcutePhase 2NCT01880437
A Study of Vismodegib in Patients With Relapsed/Refractory Acute Myelogenous Leukemia and Relapsed Refractory High-Risk Myelodysplastic Syndrome
A Phase 2 study testing cytarabine and vismodegib in people with Myelodysplastic Syndromes, Myelogenous Leukemia, Acute, run by Hoffmann-La Roche at 14 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes, Myelogenous Leukemia, Acute
- What is being tested?
- cytarabine and vismodegib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 14 sitesin 3 countries
- Study dates
- Sep 2013to Nov 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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:
Show all 9Show fewer
- 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
Trial locations and contacts
14 sites in 3 countries.
14 sites in 3 countries
United States5 sites
Study site
Ann Arbor, Michigan, 48109
Study site
Houston, Texas, 77030
Study site
Kansas City, Missouri, 64131
Study site
New York, New York, 10065
Study site
Stanford, California, 94305
Germany5 sites
Study site
Braunschweig, 38114
Study site
Essen, 45122
Study site
Hamburg, 20246
Study site
Heidelberg, 69120
Study site
Münster, 48149
Canada4 sites
Study site
Edmonton, Alberta, T6L5X8
Study site
Montreal, Quebec, H1T 2M4
Study site
Montreal, Quebec, H3T 1E2
Study site
Toronto, Ontario, M5G 2M9
About this study
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)
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.
- Being tested
- cytarabine, vismodegib
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myeloid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cytarabineDrug
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
vismodegibDrug
Also called RO5450815
Cohorts 1 and 2: 150 mg orally daily
| Study group | Role | What they receive |
|---|---|---|
| Vismodegib | Experimental | Not described Receives: Drug: cytarabine; Drug: vismodegib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 8
Secondary outcomes (6)
Percentage of Participants With CR, CRi, MLFS or PR at Anytime During Study Treatment
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.
Measured: Up to 30 days of last dose of study drug (maximum treatment duration = 225 days)
Duration of Overall Response (DOR)
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).
Measured: Up to 30 days of last dose of study drug (maximum treatment duration = 225 days)
Median Overall Survival (OS) Time
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.
Measured: 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
Measured: 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
PK data was planned to be reported only if the results of Cohort 2 are available.
Measured: Predose on Days 8, 29 and 57
Area Under the Concentration-time Curve (AUC) of Cytarabine
PK data was planned to be reported only if the results of Cohort 2 are available.
Measured: Predose, 0.25, 0.5, 1, 3, 6 hours post-dose on Days 1, 8 and 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2013 (estimated)
- Study startSep 2013
- Primary completionNov 2014
- Study completionNov 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Myelodysplastic Syndromes, Myelogenous Leukemia, AcuteStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01880437
- Sponsor's protocol ID
- GO28852
- Other IDs
- 2013-001570-14
- Status last verified
- Nov 2015
- First submitted
- 11 Jun 2013
- Last updated
- 15 Dec 2015
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01880437
- Acronym / sponsor ID
- GO28852
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- Sep 2013
- Primary completion
- Nov 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 19 Jun 2013 (estimated)
- Results
- Posted 15 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vismodegib | Experimental | Drug: cytarabine, Drug: vismodegib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cytarabineCohort 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 | Drug | Vismodegib |
| vismodegibAlso: RO5450815Cohorts 1 and 2: 150 mg orally daily | Drug | Vismodegib |
Primary outcome
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
Time frame: 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.
6 secondary outcomes
Percentage of Participants With CR, CRi, MLFS or PR at Anytime During Study Treatment
Time frame: Up to 30 days of last dose of study drug (maximum treatment duration = 225 days)
Duration of Overall Response (DOR)
Time frame: Up to 30 days of last dose of study drug (maximum treatment duration = 225 days)
Median Overall Survival (OS) Time
Time frame: 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
Time frame: 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
Time frame: Predose on Days 8, 29 and 57
Area Under the Concentration-time Curve (AUC) of Cytarabine
Time frame: Predose, 0.25, 0.5, 1, 3, 6 hours post-dose on Days 1, 8 and 29
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
14 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cytarabine and vismodegib in people with Myelodysplastic Syndromes, Myelogenous Leukemia, Acute, run by Hoffmann-La Roche at 14 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States, Germany, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2015.