LeukemiasPhase 1NCT00664677
Phase 1 Study of Terameprocol (EM-1421) in Patients With Leukemia
A Phase 1 study testing Terameprocol (EM-1421) in people with Leukemias and Acute Myeloid Leukemia (AML), run by Erimos Pharmaceuticals at 1 site in United States.
Trial summary
This study is designed to determine the safety, maximum tolerated dose,dose limiting toxicity of Terameprocol(EM-1421)and determine the pharmacokinetics (clearance from the blood)of Terameprocol(EM-1421)given as intravenous infusion three times a week in patients with leukemia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemias, Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL)
- What is being tested?
- Terameprocol (EM-1421)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2007to Jun 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Patients with histological confirmed relapsed or refractory leukemias for which no standard therapies are available that are expected to result in durable remissions. Eligible are patients with:
- acute myeloid leukemia (AML) by WHO or FAB classification
- acute lymphocytic leukemia (ALL)
- adult T cell leukemia (ATL)
- chronic myeloid leukemia in blast crisis (CML-BP) having failed Bcr-Abl specific kinase inhibitors (e.g. imatinib and/or dasatinib)
- chronic lymphocytic leukemia (CLL)
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- poor-risk myelodysplastic syndrome (MDS) [by WHO >10% blasts or IPSS groups: Int-2, high]
- chronic myelomonocytic leukemia (CMML)
- ECOG performance status of 0-1
- Negative pregnancy test within 7 days of start of study drug NOTE: Men and women of child-producing potential must use effective contraceptive methods during the study (e.g. abstinence, intrauterine device [IUD], oral contraceptive or double barrier device)
- Written informed consent
- In the absence of rapidly progressing disease, the interval from prior therapies to time of study drug administration should be a minimum of 3 weeks for cytotoxic agents or at least 5 half-lives for noncytotoxic agents. Persistent chronic toxicities from prior chemotherapy must not be greater than grade 1
- Age greater than or equal to 18 years
- Patients must have the following clinical laboratory values:
- Serum creatinine less than or equal to 2.0 mg/dl or creatinine clearance greater than 50ml/hr
- Total bilirubin less than or equal to 1.5x the upper limit of normal unless considered due to Gilbert's syndrome
- Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) less than or equal to 3x the upper limit of normal unless considered due to organ leukemic involvement
Who cannot join
- Patients with any one of the following criteria will not be eligible for study participation:
- Uncontrolled intercurrent illness including, but not limited to,
- uncontrolled infection,
- myocardial infarction within previous 3 months,
- symptomatic congestive heart failure (New York Heart Association Class III, IV),
- symptomatic coronary artery disease
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- cardiac arrhythmia not controlled by medication NOTE: Patients with controlled infection on antibiotic or antifungal therapy are eligible
- Psychiatric illness/social situations that would limit compliance with study requirements or unwillingness or inability to comply with procedures required in this protocol
- Patients receiving any other standard or investigational treatment for their leukemia NOTE: Hydroxyurea is allowed prior to study drug start and for the first 7 days of therapy
- Pregnant and nursing patients are excluded. NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1
- Patients with known CNS disease
- History of allergic reactions attributed to compounds of similar chemical or biological composition to Terameprocol (EM-1421) or excipients
Trial locations and contacts
1 site in 1 country.
United States1 site
UNC, Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
About this study
Official title: Phase 1 Study of Terameprocol (EM-1421) a Survivin and Cyclin-Dependent Kinase-1 (Cdc2) Inhibitor, in Patients With Leukemia
This study is designed to determine the safety, maximum tolerated dose,dose limiting toxicity of Terameprocol(EM-1421)and determine the pharmacokinetics (clearance from the blood)of Terameprocol(EM-1421)given as intravenous infusion three times a week in patients with leukemia.
Read the detailed description
The dose of Terameprocol (EM-1421) will be escalated in successive cohorts of 3 patients. Patients will be entered sequentially on each dose level. If none of the first 3 patients at a dose level experience first cycle drug related dose-limiting toxicity (DLT), new patients may be entered at the next higher dose level. If 1 of 3 patients experience first cycle DLT, up to 3 more patients are started at that same dose level. If 2 or more experience first cycle DLT, no further patients are started at that dose. The MTD is the highest dose level in which <2 patients of 6 develop a first cycle DLT. New dose levels may begin accrual only if all patients at the current dose level have been observed for a minimum of 3 weeks after the last infusion of Terameprocol (EM-1421). The recommended phase 2 dose (RP2D) will be the MTD unless significant clinical activity is seen below the MTD.
During the observation period of 3 weeks, additional accrual to a previously assessed lower dose level, with no documented DLTs, will be allowed with sponsor approval.
Patients will be treated three times a week, with at least one day in between infusions, for two weeks followed by one week of rest. The dose for new cohorts will be escalated from 1000, to 1500 and 2200 mg or de-escalated to 500 mg if 1000 mg exceeds the MTD. The principal investigator will consult with the sponsor to determine the appropriate dose level for a new patient. At the MTD, up to 10 additional patients may be accrued in that dose cohort to further define the toxicities and response of the agent. If the initial dose level exceeds the MTD, a fallback dose level of 500 mg will be implemented.
Patients are allowed to be treated with subsequent cycles of Terameprocol (EM-1421) until disease progression or until severe toxicities occur and side effects do not outweigh the benefit of study drug administration in the assessment of the treating physician.
Intrapatient dose escalation Intrapatient dose escalation by one dose level may be permitted, but only if at least 3 patients in the next higher dose level have been treated and have been followed for 21 days without experiencing DLT. Decisions for intrapatient dose escalation will be made jointly by the Study Sponsor, treating physician and Principal Investigator.
Terameprocol (EM-1421) as a single agent given intravenously over 6 hours three times a week for two weeks followed by one week rest (two weeks on, one week off)in the following dose cohorts starting with 1000 mg dose cohort.
Dose Level -1: 500 mg
Dose Level 1: 1000 mg
Dose Level 2: 1500 mg
Dose Level 3: 2200 mg
- Conditions
- Leukemias, Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Adult T Cell Leukemia (ATL), Chronic Myeloid Leukemia (CML-BP), Chronic Lymphocytic Leukemia (CLL)
- Being tested
- Terameprocol (EM-1421)
- Keywords
- Adult, Leukemia, Terameprocol, Survivin, AML, ALL, ATL, CML, CLL, CMML, MDS
- Medical subject headings
- Leukemia, Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Lymphocytic, Chronic, B-Cell, Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Terameprocol (EM-1421)Drug
Also called Terameprocol, EM-1421, meso-Tetra-o-Methyl Nordihydroguaiaretic Acid
Terameprocol (EM-1421) as a single agent given intravenously over 6 hours three times a week for two weeks followed by one week rest (two weeks on, one week off.
| Study group | Role | What they receive |
|---|---|---|
| Terameprocol (EM-1421) | Experimental | Terameprocol (EM-1421) as a single agent given intravenously over 6 hours three times a week for two weeks followed by one week rest (two weeks on, one week off). Receives: Drug: Terameprocol (EM-1421) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety, maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of Terameprocol (EM-1421) given as intravenous infusion three times a week in patients with leukemia
Measured: Adverse events and toxicity will be assessed prior to each cycle of treatment and at times when clinically indicated.
Secondary outcomes (2)
Pharmacokinetics (PK) of Terameprocol (EM-1421) given as intravenous infusion three times a week in patients with leukemia
Measured: Pharmacokinetics samples will be collected only on the first cycle of treatment with study drug from immediately prior to first study drug infusion to the end of day 12 of infusion.
To access anti-tumor activity
Measured: Pharmacodynamic (molecular markers) samples will be collected immediately prior to, day 5 pre-dose and post-dose day 12 of each cycle of study drug administration, at remission and at relapse/or end of study (whichever occurs first).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2008 (estimated)
- Study startAug 2007
- Primary completionMar 2009
- Study completionJun 2009
Why it stopped: Funding constraints
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiasStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erimos Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Neil Frazer, MB, ChB, Study director, Erimos Pharmaceutical
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00664677
- Sponsor's protocol ID
- EM-1421 #105
- Status last verified
- Feb 2016
- First submitted
- 21 Apr 2008
- Last updated
- 23 Feb 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of Terameprocol (EM-1421) a Survivin and Cyclin-Dependent Kinase-1 (Cdc2) Inhibitor, in Patients With Leukemia
- ClinicalTrials.gov ID
- NCT00664677
- Acronym / sponsor ID
- EM-1421 #105
- Conditions
- Leukemias, Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Adult T Cell Leukemia (ATL), Chronic Myeloid Leukemia (CML-BP), Chronic Lymphocytic Leukemia (CLL)
- Keywords
- Adult, Leukemia, Terameprocol, Survivin, AML, ALL, ATL, CML
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding constraints
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Erimos PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Aug 2007
- Primary completion
- Mar 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 23 Apr 2008 (estimated)
- Results
- Not posted in the source record
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 designed to determine the safety, maximum tolerated dose,dose limiting toxicity of Terameprocol(EM-1421)and determine the pharmacokinetics (clearance from the blood)of Terameprocol(EM-1421)given as intravenous infusion three times a week in patients with leukemia.
Detailed description
The dose of Terameprocol (EM-1421) will be escalated in successive cohorts of 3 patients. Patients will be entered sequentially on each dose level. If none of the first 3 patients at a dose level experience first cycle drug related dose-limiting toxicity (DLT), new patients may be entered at the next higher dose level. If 1 of 3 patients experience first cycle DLT, up to 3 more patients are started at that same dose level. If 2 or more experience first cycle DLT, no further patients are started at that dose. The MTD is the highest dose level in which <2 patients of 6 develop a first cycle DLT. New dose levels may begin accrual only if all patients at the current dose level have been observed for a minimum of 3 weeks after the last infusion of Terameprocol (EM-1421). The recommended phase 2 dose (RP2D) will be the MTD unless significant clinical activity is seen below the MTD.
During the observation period of 3 weeks, additional accrual to a previously assessed lower dose level, with no documented DLTs, will be allowed with sponsor approval.
Patients will be treated three times a week, with at least one day in between infusions, for two weeks followed by one week of rest. The dose for new cohorts will be escalated from 1000, to 1500 and 2200 mg or de-escalated to 500 mg if 1000 mg exceeds the MTD. The principal investigator will consult with the sponsor to determine the appropriate dose level for a new patient. At the MTD, up to 10 additional patients may be accrued in that dose cohort to further define the toxicities and response of the agent. If the initial dose level exceeds the MTD, a fallback dose level of 500 mg will be implemented.
Patients are allowed to be treated with subsequent cycles of Terameprocol (EM-1421) until disease progression or until severe toxicities occur and side effects do not outweigh the benefit of study drug administration in the assessment of the treating physician.
Intrapatient dose escalation Intrapatient dose escalation by one dose level may be permitted, but only if at least 3 patients in the next higher dose level have been treated and have been followed for 21 days without experiencing DLT. Decisions for intrapatient dose escalation will be made jointly by the Study Sponsor, treating physician and Principal Investigator.
Terameprocol (EM-1421) as a single agent given intravenously over 6 hours three times a week for two weeks followed by one week rest (two weeks on, one week off)in the following dose cohorts starting with 1000 mg dose cohort.
Dose Level -1: 500 mg
Dose Level 1: 1000 mg
Dose Level 2: 1500 mg
Dose Level 3: 2200 mg
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Terameprocol (EM-1421) | Experimental | Drug: Terameprocol (EM-1421)Terameprocol (EM-1421) as a single agent given intravenously over 6 hours three times a week for two weeks followed by one week rest (two weeks on, one week off). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patients with histological confirmed relapsed or refractory leukemias for which no standard therapies are available that are expected to result in durable remissions. Eligible are patients with:
- ECOG performance status of 0-1
- Negative pregnancy test within 7 days of start of study drug NOTE: Men and women of child-producing potential must use effective contraceptive methods during the study (e.g. abstinence, intrauterine device [IUD], oral contraceptive or double barrier device)
- Written informed consent
- In the absence of rapidly progressing disease, the interval from prior therapies to time of study drug administration should be a minimum of 3 weeks for cytotoxic agents or at least 5 half-lives for noncytotoxic agents. Persistent chronic toxicities from prior chemotherapy must not be greater than grade 1
Key exclusion criteria (13 listed)
- Patients with any one of the following criteria will not be eligible for study participation:
- Uncontrolled intercurrent illness including, but not limited to,
- Psychiatric illness/social situations that would limit compliance with study requirements or unwillingness or inability to comply with procedures required in this protocol
- Patients receiving any other standard or investigational treatment for their leukemia NOTE: Hydroxyurea is allowed prior to study drug start and for the first 7 days of therapy
- Pregnant and nursing patients are excluded. NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
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 |
|---|---|---|
| Terameprocol (EM-1421)Also: Terameprocol, EM-1421, meso-Tetra-o-Methyl Nordihydroguaiaretic AcidTerameprocol (EM-1421) as a single agent given intravenously over 6 hours three times a week for two weeks followed by one week rest (two weeks on, one week off. | Drug | Terameprocol (EM-1421) |
Primary outcome
Safety, maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of Terameprocol (EM-1421) given as intravenous infusion three times a week in patients with leukemia
Time frame: Adverse events and toxicity will be assessed prior to each cycle of treatment and at times when clinically indicated.
2 secondary outcomes
Pharmacokinetics (PK) of Terameprocol (EM-1421) given as intravenous infusion three times a week in patients with leukemia
Time frame: Pharmacokinetics samples will be collected only on the first cycle of treatment with study drug from immediately prior to first study drug infusion to the end of day 12 of infusion.
To access anti-tumor activity
Time frame: Pharmacodynamic (molecular markers) samples will be collected immediately prior to, day 5 pre-dose and post-dose day 12 of each cycle of study drug administration, at remission and at relapse/or end of study (whichever occurs first).
Results and safety
The study was stopped early (reason given: Funding constraints). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2016.
- Link to pubmed abstract of publication Tibes et al., Investigational New Drugs April 2015, Volume 33, Issue 2, pp 389-396Link provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Neil Frazer, MB, ChB study director
Erimos Pharmaceutical
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Terameprocol (EM-1421) in people with Leukemias and Acute Myeloid Leukemia (AML), run by Erimos Pharmaceuticals at 1 site in United States.
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 17 inclusion and 13 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 23 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 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?
The study was stopped early (reason given: Funding constraints). Results are not available in the source record.
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?
Safety, maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of Terameprocol (EM-1421) given as intravenous infusion three times a week in patients with leukemia (time frame: Adverse events and toxicity will be assessed prior to each cycle of treatment and at times when clinically indicated.). 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 23 Feb 2016.