Acute Myeloid LeukemiaPhase 1/2NCT00878722
Trial of PXD101 (Belinostat) in Combination With Idarubicin to Treat AML Not Suitable for Standard Intensive Therapy
A Phase 1/2 study testing PXD101 and idarubicin in people with Acute Myeloid Leukemia, run by Valerio Therapeutics at 6 sites in 3 countries.
Trial summary
An open-label, non-randomized, multi-centre, Phase I/II trial to assess the efficacy and safety of 2 schedules of PXD101 in combination with idarubicin in patients with AML not suitable for standard intensive therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- PXD101 and idarubicin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 6 sitesin 3 countries
- Study dates
- Aug 2007to Apr 2012
- Phase
- Phase 1/2
- 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
- Signed consent
- AML patients:
- above 60 years in first relapse or refractory.
- 18-60 years 2nd relapse or refractory to at least two intensive chemotherapy regimens.
- above 60 years with high risk features (cytogenetics, secondary or treatment related AML) d) above 60 years with myelodysplastic syndrome with >10% blasts in bone marrow (WHO RAEB-2 (Refractory anemia with excess blasts-2)). For patients below 60 years potential curative treatments should have been exhausted.
- Performance status (ECOG) ≤ 2
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- Age ≥ 18 years
- Acceptable liver, renal and bone marrow function as defined
- Serum potassium within normal range.
- Acceptable coagulation status as defined
- Precautions for female patients with reproductive potential as defined
Who cannot join
- Treatment with investigational agents within the last 4 weeks
- Prior treatment with HDAC (Histone deacetylases) inhibitors including valproic acid
- Prior anti-leukemic therapy (except hydroxyurea) within the last 3 weeks of trial dosing
- Co-existing active infection (including HIV) or any co-existing medical condition likely to interfere with trial procedures, including significant cardiovascular disease
- Altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures.
- Concurrent second malignancy.
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- History of hypersensitivity to idarubicin
- Cumulative idarubicin dose exceeding 100 mg/m², or a (with respect cardiotoxicity) corresponding dose of other anthracyclines
- LVEF (left ventricular ejection fraction) below normal range (< 45% )
- Known Central Nervous System (CNS) leukemia
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
Germany3 sites
Uniklinik Homburg
Homburg, 66424
Uni Hospital Marburg
Marburg, 35043
Universitätsklinikum Ulm
Ulm, 89081
About this study
Official title: A Phase I/II Clinical Trial of PXD101 in Combination With Idarubicin in Patients With AML Not Suitable for Standard Intensive Therapy
An open-label, non-randomized, multi-centre, Phase I/II trial to assess the efficacy and safety of 2 schedules of PXD101 in combination with idarubicin in patients with AML not suitable for standard intensive therapy.
Read the detailed description
This trial is an open-label, multi-centre, dose-escalation Phase I/II study to evaluate safety, explore efficacy, pharmacodynamics, and pharmacokinetics of the combination of PXD101 with idarubicin administered in two different schedules in patients with AML. The PXD101 plus idarubicin treatment will be repeated at suitable intervals (target is every 3 weeks for schedule A and every 2 weeks for schedule B) depending upon toxicities or disease progression. Safety and efficacy assessments will be performed at every cycle.
Schedule A uses PXD101 by 30 min infusion daily for 5 days every 3 weeks with escalating doses of idarubicin.
Schedule B uses escalating doses of continuous infusion (48h) of PXD101 alone or in combination with idarubicin.
In both regimens the trial may be expanded at the Maximum Tolerated Dose (MTD).
- Conditions
- Acute Myeloid Leukemia
- Being tested
- PXD101, idarubicin
- Keywords
- Acute Myeloid Leukemia, PXD101, Belinostat, Idarubicin
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PXD101Drug
Also called Belinostat
idarubicinDrug
Also called Zavedos
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | PXD101 administered as a 30-minute intravenous (IV) infusion of 1000 mg/m²/d for five consecutive days every 3 weeks.
Idarubicin administered on day 5 (first steps) or days 4 and 5 (later steps). Patients will be treated in a 21-day cycle for a minimum of 2 cycles and a maximum of 6 cycles (depending on cumulated idarubicin dose). Receives: Drug: PXD101; Drug: idarubicin |
| Arm B | Experimental | PXD101 administered by continuous intravenous infusion over 24-48 hours and idarubicin (in the later steps) added after the first 24 hours. The second cycle will start on day 15 but under observation of possible toxicity. Further cycles will be administered q 14 d for up to 6 cycles. The first dose steps will be carried out with PXD101 alone for safety reasons. Receives: Drug: PXD101; Drug: idarubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose, Dose Limiting Toxicity
DLT (dose limiting toxicities): patients with any of the toxicities: 1.Haematological toxicity is not included in the definition due to bone marrow involvement by the disease except for following grade 4 ANC (absolute neutrophil count) and PLT (platelet count) for 6 weeks with less than 5% blasts in bone marrow. 2.Drug related non hematological Grade 3 or 4 toxicity except alopecia, brief nausea and vomiting, diarrhea, rash, arthralgias and myalgias. Treatment interventions should palliate toxicity symptoms prior to concluding a DLT has occurred (e.g if nausea and vomiting to Grade 3 have been associated with the drug). If despite standard treatment Grade 3 nausea and or vomiting persisted then a DLT was considered to have occurred. Grade 4 diarrhea in spite of standard therapeutic measures was included in DLT definition. 3.Inability to tolerate full dosing cycle due to toxicity or any drug-related adverse event resulting in more than 14 day treatment delay in the next treatment cycle
Measured: First Cycle
Overall Response
Efficacy measured as Response rate (complete response ([CR] and Complete remission with incomplete recovery of platelets [CRi]) and partial response ([PR])) using the response criteria of the International Working Group (Cheson et al 2003). CR includes CRi, CRc (Cytogenetic complete remission), and CRm (Molecular complete remission).
Measured: Throughout study, after each cycle for the first two cycles, then after every second cycle
Secondary outcomes (9)
Time to Response (CR and PR)
Time to response: time in weeks from first treatment to obtainment of the particular response status (CR and PR)
Measured: Throughout study, after each cycle for the first two cycles, then after every second cycle
Duration of Response (CR and PR)
Duration of Response (CR and PR) in Weeks
Measured: Throughout study, after each cycle for the first two cycles, then after every second cycle
Overall Survival
Overall survival: time in weeks from entry into study until death from any cause. All patients without this endpoint at the time of discontinuation or the end of trial have been censored.
Measured: Throughout study, after each cycle for the first two cycles, then after every second cycle
Relapse-Free Survival
Relapse-free survival: time (weeks) from leukemia-free state to relapse or death from any cause.
Measured: Throughout study, after each cycle for the first two cycles, then after every second cycle
Event-Free Survival
Event-free survival: time (weeks) from entry into study until treatment failure, disease relapse or death from any cause.
Measured: Throughout study, after each cycle for the first two cycles, then after every second cycle
Remission Duration
Remission duration: time (weeks) from date of remission status to disease relapse.
Measured: Throughout study, after each cycle for the first two cycles, then after every second cycle
Belinostat Cmax
Cmax: Arm A: at Cycle 1 Day 4, Cycle 1 Day 5 Arm B: Cycle 1 Day 1 and Cycle 1 Day 2
Measured: Samples taken in Cycle 1 only, prior to initial dose on days 4 and 5 and at end of infusion, 5, 15, and 30 min, and 1, 2, 3, 4, and 6 hours post infusion
Belinostat AUC (Area Under Curve)
Measured: Cycle 1, prior to initial dose on days 4 and 5 and at end of infusion, 5, 15, and 30 min, and 1, 2, 3, 4, and 6 hours post infusion
Elimination t½
Measured: Cycle 1, Samples taken in Cycle 1 only, prior to initial dose on days 4 and 5 and at end of infusion, 5, 15, and 30 min, and 1, 2, 3, 4, and 6 hours post infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2009 (estimated)
- Study startAug 2007
- Primary completionMay 2009
- Study completionApr 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.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Valerio Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- e-mail contact via enquiries@topotarget.com, Study chair, Valerio Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00878722
- Sponsor's protocol ID
- PXD101-CLN-15
- Status last verified
- Jul 2015
- First submitted
- 7 Apr 2009
- Last updated
- 28 Jul 2015
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Clinical Trial of PXD101 in Combination With Idarubicin in Patients With AML Not Suitable for Standard Intensive Therapy
- ClinicalTrials.gov ID
- NCT00878722
- Acronym / sponsor ID
- PXD101-CLN-15
- Conditions
- Acute Myeloid Leukemia
- Keywords
- Acute Myeloid Leukemia, PXD101, Belinostat, Idarubicin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Valerio TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Aug 2007
- Primary completion
- May 2009 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 9 Apr 2009 (estimated)
- Results
- Posted 13 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An open-label, non-randomized, multi-centre, Phase I/II trial to assess the efficacy and safety of 2 schedules of PXD101 in combination with idarubicin in patients with AML not suitable for standard intensive therapy.
Detailed description
This trial is an open-label, multi-centre, dose-escalation Phase I/II study to evaluate safety, explore efficacy, pharmacodynamics, and pharmacokinetics of the combination of PXD101 with idarubicin administered in two different schedules in patients with AML. The PXD101 plus idarubicin treatment will be repeated at suitable intervals (target is every 3 weeks for schedule A and every 2 weeks for schedule B) depending upon toxicities or disease progression. Safety and efficacy assessments will be performed at every cycle.
Schedule A uses PXD101 by 30 min infusion daily for 5 days every 3 weeks with escalating doses of idarubicin.
Schedule B uses escalating doses of continuous infusion (48h) of PXD101 alone or in combination with idarubicin.
In both regimens the trial may be expanded at the Maximum Tolerated Dose (MTD).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: PXD101, Drug: idarubicinPXD101 administered as a 30-minute intravenous (IV) infusion of 1000 mg/m²/d for five consecutive days every 3 weeks. Idarubicin administered on day 5 (first steps) or days 4 and 5 (later steps). Patients will be treated in a 21-day cycle for a minimum of 2 cycles and a maximum of 6 cycles (depending on cumulated idarubicin dose). |
| Arm B | Experimental | Drug: PXD101, Drug: idarubicinPXD101 administered by continuous intravenous infusion over 24-48 hours and idarubicin (in the later steps) added after the first 24 hours. The second cycle will start on day 15 but under observation of possible toxicity. Further cycles will be administered q 14 d for up to 6 cycles. The first dose steps will be carried out with PXD101 alone for safety reasons. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Signed consent
- AML patients:
- Performance status (ECOG) ≤ 2
- Age ≥ 18 years
- Acceptable liver, renal and bone marrow function as defined
Key exclusion criteria (10 listed)
- Treatment with investigational agents within the last 4 weeks
- Prior treatment with HDAC (Histone deacetylases) inhibitors including valproic acid
- Prior anti-leukemic therapy (except hydroxyurea) within the last 3 weeks of trial dosing
- Co-existing active infection (including HIV) or any co-existing medical condition likely to interfere with trial procedures, including significant cardiovascular disease
- Altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures.
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 |
|---|---|---|
| PXD101Also: Belinostat | Drug | Arm A, Arm B |
| idarubicinAlso: Zavedos | Drug | Arm A, Arm B |
Primary outcome
Maximum Tolerated Dose, Dose Limiting Toxicity
Time frame: First Cycle
DLT (dose limiting toxicities): patients with any of the toxicities: 1.Haematological toxicity is not included in the definition due to bone marrow involvement by the disease except for following grade 4 ANC (absolute neutrophil count) and PLT (platelet count) for 6 weeks with less than 5% blasts in bone marrow. 2.Drug related non hematological Grade 3 or 4 toxicity except alopecia, brief nausea and vomiting, diarrhea, rash, arthralgias and myalgias. Treatment interventions should palliate toxicity symptoms prior to concluding a DLT has occurred (e.g if nausea and vomiting to Grade 3 have been associated with the drug). If despite standard treatment Grade 3 nausea and or vomiting persisted then a DLT was considered to have occurred. Grade 4 diarrhea in spite of standard therapeutic measures was included in DLT definition. 3.Inability to tolerate full dosing cycle due to toxicity or any drug-related adverse event resulting in more than 14 day treatment delay in the next treatment cycle
Overall Response
Time frame: Throughout study, after each cycle for the first two cycles, then after every second cycle
Efficacy measured as Response rate (complete response ([CR] and Complete remission with incomplete recovery of platelets [CRi]) and partial response ([PR])) using the response criteria of the International Working Group (Cheson et al 2003). CR includes CRi, CRc (Cytogenetic complete remission), and CRm (Molecular complete remission).
9 secondary outcomes
Time to Response (CR and PR)
Time frame: Throughout study, after each cycle for the first two cycles, then after every second cycle
Duration of Response (CR and PR)
Time frame: Throughout study, after each cycle for the first two cycles, then after every second cycle
Overall Survival
Time frame: Throughout study, after each cycle for the first two cycles, then after every second cycle
Relapse-Free Survival
Time frame: Throughout study, after each cycle for the first two cycles, then after every second cycle
Event-Free Survival
Time frame: Throughout study, after each cycle for the first two cycles, then after every second cycle
Remission Duration
Time frame: Throughout study, after each cycle for the first two cycles, then after every second cycle
Belinostat Cmax
Time frame: Samples taken in Cycle 1 only, prior to initial dose on days 4 and 5 and at end of infusion, 5, 15, and 30 min, and 1, 2, 3, 4, and 6 hours post infusion
Belinostat AUC (Area Under Curve)
Time frame: Cycle 1, prior to initial dose on days 4 and 5 and at end of infusion, 5, 15, and 30 min, and 1, 2, 3, 4, and 6 hours post infusion
Elimination t½
Time frame: Cycle 1, Samples taken in Cycle 1 only, prior to initial dose on days 4 and 5 and at end of infusion, 5, 15, and 30 min, and 1, 2, 3, 4, and 6 hours post infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 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.
e-mail contact via enquiries@topotarget.com study chair
Valerio Therapeutics
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PXD101 and idarubicin in people with Acute Myeloid Leukemia, run by Valerio Therapeutics at 6 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 11 inclusion and 10 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 28 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Germany, France, United Kingdom. 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 combined 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.
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 13 Nov 2014). 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?
Maximum Tolerated Dose, Dose Limiting Toxicity (time frame: First Cycle). The study lists 2 primary outcomes in all. 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 28 Jul 2015.