Leukemia, Myelocytic, Acute Myelodysplastic SyndromesPhase 1NCT00479232
Phase I Trial of Vorinostat (MK-0683, SAHA) in Combination With Decitabine in Patients With AML or MDS (MK-0683-055 EXT1)
A Phase 1 study testing vorinostat and decitabine in people with Leukemia, Myelocytic, Acute Myelodysplastic Syndromes and Myelodysplastic Syndromes, run by Merck Sharp & Dohme LLC.
Trial summary
This study is to evaluate the safety and tolerability of vorinostat in combination with decitabine as well as the in vivo molecular and biological effects of vorinostat in patients with refractory or relapsed Acute Myelogenous Leukemia (AML) and intermediate or high risk as defined by International Prognostic Scoring… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Myelocytic, Acute Myelodysplastic Syndromes, Myelodysplastic Syndromes
- What is being tested?
- vorinostat and decitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 71 participants
- Where
- No sites listed yet
- Study dates
- Jun 2007to Mar 2012
- Phase
- Phase 1
- 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
- Patient is at least 18 years old with refractory/relapsed AML
- If untreated AML, patient is older than 60 years old and not a candidate for standard chemotherapy
- Patient is at least 4 weeks from prior treatment and has recovered from all prior treatment side effects
- Patient has no known liver or kidney problems
- Patient knows of no reason they can not receive transfusions of blood clotting cells (platelets)
- Patient is able to swallow capsules
- Patients both male and female are willing to practice birth control during the study
Who cannot join
- Patient has received prior treatment with valproic acid, decitabine or azacitidine
- Being is less than 18 years of age or if patient has untreated AML is below 60 years of age
- Patient is a women who is pregnant or breastfeeding. Patient has an active infection that requires antibiotics
- Patient has uncontrolled illness including but not limited to the following: heart problems (congestive heart failure, unstable angina pectoris, cardiac arrhythmia), inflammation of the pancreas; a mental or social condition that may interfere with patient following study procedures
- Patient has known human immunodeficiency virus (HIV) infection or HIV-related malignancy. Patient has a known history of hepatitis B or C infection
- Patient currently has another active cancer other than certain types of skin cancer
- Patient is heterosexual and able to have a child and is unwilling to practice birth control during the study
About this study
Official title: A Phase I Clinical Trial of Vorinostat in Combination With Decitabine in Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndrome
This study is to evaluate the safety and tolerability of vorinostat in combination with decitabine as well as the in vivo molecular and biological effects of vorinostat in patients with refractory or relapsed Acute Myelogenous Leukemia (AML) and intermediate or high risk as defined by International Prognostic Scoring System (IPSS) Myelodysplastic Syndrome (MDS). Participants with Acute Myelogenous Leukemia or Myelodysplastic Syndrome are eligible.
- Being tested
- vorinostat, decitabine
- Keywords
- Leukemia, Myelocytic, Acute Myelodysplastic Syndromes
- Medical subject headings
- Leukemia, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vorinostatDrug
Also called MK-0683, SAHA
decitabineDrug
Also called Dacogen
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Vorinostat (sequential) | Experimental | Vorinostat 400 mg capsules once daily given 7, 10 or 14 days in 28 day cycles. Up to 24 months of treatment.
Decitabine IV 20 mg/m^2 daily for 5 days in each 28 day cycle. Up to 24 months of treatment. Receives: Drug: vorinostat; Drug: decitabine |
| Cohort 2: Vorinostat (concurrent) | Experimental | Vorinostat 400 mg capsules once daily given 7 days, 14 days with 8 day break after first 7 days or 14 days without break, out of 28 day cycles.
Decitabine IV 20 mg/m^2 daily for 5 days in each 28 day cycle. Up to 24 months of treatment. Receives: Drug: vorinostat; Drug: decitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Experiencing Dose Limiting Toxicity (DLT) Events
Participants who received at least one dose of vorinostat in combination with decitabine intravenous (IV) at a dose of 20 mg/m^2 daily for 5 days along with oral vorinostat 400 mg once daily for 7 to 14 days in a 28-day cycle concurrently or sequentially, were evaluated to determine the maximum tolerable dose (MTD) determined by the number of participants experiencing dose limiting toxicity (DLT) events defined as any Grade 3 or 4 non-hematological toxicity (reported adverse event) and/or myelosuppression lasting >42 days.
Measured: Day 1 to 28 of Cycle 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2007 (estimated)
- Study startJun 2007
- Primary completionApr 2010
- Study completionMar 2012
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Leukemia, Myelocytic, Acute Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00479232
- Sponsor's protocol ID
- 0683-055
- Other IDs
- 2007_500
- Status last verified
- Sep 2015
- First submitted
- 24 May 2007
- Last updated
- 21 Sep 2015
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Kirschbaum M, Gojo I, Goldberg SL, Bredeson C, Kujawski LA, Yang A, Marks P, Frankel P, Sun X, Tosolini A, Eid JE, Lubiniecki GM, Issa JP. A phase 1 clinical trial of vorinostat in combination with decitabine in patients with acute myeloid leukaemia or myelodysplastic syndrome. Br J Haematol. 2014 Oct;167(2):185-93. doi: 10.1111/bjh.13016. Epub 2014 Jul 8.
PubMed 25040094
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Clinical Trial of Vorinostat in Combination With Decitabine in Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndrome
- ClinicalTrials.gov ID
- NCT00479232
- Acronym / sponsor ID
- 0683-055
- Keywords
- Leukemia, Myelocytic, Acute Myelodysplastic Syndromes
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 71 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- Jun 2007
- Primary completion
- Apr 2010 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 28 May 2007 (estimated)
- Results
- Posted 31 Aug 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is to evaluate the safety and tolerability of vorinostat in combination with decitabine as well as the in vivo molecular and biological effects of vorinostat in patients with refractory or relapsed Acute Myelogenous Leukemia (AML) and intermediate or high risk as defined by International Prognostic Scoring System (IPSS) Myelodysplastic Syndrome (MDS). Participants with Acute Myelogenous Leukemia or Myelodysplastic Syndrome are eligible.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Vorinostat (sequential) | Experimental | Drug: vorinostat, Drug: decitabineVorinostat 400 mg capsules once daily given 7, 10 or 14 days in 28 day cycles. Up to 24 months of treatment. Decitabine IV 20 mg/m^2 daily for 5 days in each 28 day cycle. Up to 24 months of treatment. |
| Cohort 2: Vorinostat (concurrent) | Experimental | Drug: vorinostat, Drug: decitabineVorinostat 400 mg capsules once daily given 7 days, 14 days with 8 day break after first 7 days or 14 days without break, out of 28 day cycles. Decitabine IV 20 mg/m^2 daily for 5 days in each 28 day cycle. Up to 24 months of treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patient is at least 18 years old with refractory/relapsed AML
- Patient is at least 4 weeks from prior treatment and has recovered from all prior treatment side effects
- Patient has no known liver or kidney problems
- Patient knows of no reason they can not receive transfusions of blood clotting cells (platelets)
- Patient is able to swallow capsules
Key exclusion criteria (7 listed)
- Patient has received prior treatment with valproic acid, decitabine or azacitidine
- Being is less than 18 years of age or if patient has untreated AML is below 60 years of age
- Patient is a women who is pregnant or breastfeeding. Patient has an active infection that requires antibiotics
- Patient has uncontrolled illness including but not limited to the following: heart problems (congestive heart failure, unstable angina pectoris, cardiac arrhythmia), inflammation of the pancreas; a mental or social condition that may interfere with patient following study procedures
- Patient has known human immunodeficiency virus (HIV) infection or HIV-related malignancy. Patient has a known history of hepatitis B or C infection
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 |
|---|---|---|
| vorinostatAlso: MK-0683, SAHA | Drug | Cohort 1: Vorinostat (sequential), Cohort 2: Vorinostat (concurrent) |
| decitabineAlso: Dacogen | Drug | Cohort 1: Vorinostat (sequential), Cohort 2: Vorinostat (concurrent) |
Primary outcome
Number of Participants Experiencing Dose Limiting Toxicity (DLT) Events
Time frame: Day 1 to 28 of Cycle 1
Participants who received at least one dose of vorinostat in combination with decitabine intravenous (IV) at a dose of 20 mg/m^2 daily for 5 days along with oral vorinostat 400 mg once daily for 7 to 14 days in a 28-day cycle concurrently or sequentially, were evaluated to determine the maximum tolerable dose (MTD) determined by the number of participants experiencing dose limiting toxicity (DLT) events defined as any Grade 3 or 4 non-hematological toxicity (reported adverse event) and/or myelosuppression lasting >42 days.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25040094Kirschbaum M, Gojo I, Goldberg SL, Bredeson C, Kujawski LA, Yang A, Marks P, Frankel P, Sun X, Tosolini A, Eid JE, Lubiniecki GM, Issa JP. A phase 1 clinical trial of vorinostat in combination with decitabine in patients with acute myeloid leukaemia or myelodysplastic syndrome. Br J Haematol. 2014 Oct;167(2):185-93. doi: 10.1111/bjh.13016. Epub 2014 Jul 8.
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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.
Medical Monitor study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing vorinostat and decitabine in people with Leukemia, Myelocytic, Acute Myelodysplastic Syndromes and Myelodysplastic Syndromes, run by Merck Sharp & Dohme LLC.
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 7 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: finished, as of the sponsor's last update on 21 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 31 Aug 2011). 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?
Number of Participants Experiencing Dose Limiting Toxicity (DLT) Events (time frame: Day 1 to 28 of Cycle 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00479232, which also lists 1 linked publication.
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 21 Sep 2015.