Acute Myeloid LeukemiaPhase 1NCT00718159
Study of LY573636-sodium in Essential Thrombocythemia and Acute Myeloid Leukemia
A Phase 1 study testing LY573636-sodium in people with Acute Myeloid Leukemia and Essential Thrombocythemia, run by Eli Lilly and Company at 5 sites in United States.
Trial summary
The purpose of this study is to determine a safe dose of LY573636-sodium to be given to patients with acute myeloid leukemia and to determine any side effects that may be associated with LY573636-sodium in this patient population. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Essential Thrombocythemia
- What is being tested?
- LY573636-sodium
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 5 sitesUnited States
- Study dates
- Aug 2008to Dec 2011
- 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
- Participants who have a diagnosis of either essential thrombocythemia or acute myeloid leukemia that is relapsed or refractory to at least one prior standard treatment. If participants have acute promyelocytic leukemia, they must be resistant and/or intolerant of both all trans retinoic acid (ATRA) and arsenic trioxide.
- Are at least 18 years of age.
- Have given written informed consent approved by Lilly and the ethical review board (ERB)/institutional review board (IRB) governing the site.
- Must have adequate hepatic and renal function.
- Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, immunotherapy, cancer-related hormonal therapy, or other investigational therapy for at least 21 days for myelosuppressive agents (such as cytarabine, daunorubicin, and gemtuzumab ozogamicin) or 14 days for non-myelosuppressive agents prior to receiving study drug and recovered from the acute effects of therapy. Hydroxyurea used to control peripheral blood blast count is permitted within these respective periods, but it must be stopped at least 24 hours before study drug administration.
- Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 6 months following the last dose of study drug.
- Females of child bearing potential must have had a negative serum pregnancy test less than or equal to 7 days prior to the first dose of study drug.
- Have a serum albumin level greater than equal to 3.0 grams/deciliter (g/L), less than or equal to 72 hour prior to dosing with LY573636-sodium.
Who cannot join
- Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of the initial dose of study drug for a non-myelosuppressive or myelosuppressive agent, respectively.
- Participants with myeloproliferative disorders (for example, chronic myeloid leukemia (CML), polycythemia vera and primary myelofibrosis) other than essential thrombocythemia.
- Have received an autologous or allogenic stem cell transplant within 75 days of the initial dose of study drug for the dose escalation phase or within 60 days of the initial dose of study drug for the dose confirmation phase. Recipients of an allogeneic stem cell transplant must have discontinued immunosuppressive therapy at least 24 hours before study drug administration with no more than Grade 1 acute graft-versus-host disease.
- Have previously completed or withdrawn from this study or any other study investigating LY573636 sodium.
- Have serious preexisting medical conditions that in the opinion of the investigator would preclude participation in this study.
- Have serious concomitant disorders, including active bacterial, fungal, or viral infection, incompatible with the study.
Show all 15Show fewer
- Have a second primary malignancy that could affect interpretation of results.
- Have a known coagulopathy or bleeding disorder, other than leukemic related thrombocytopenia. Participants with severe or life-threatening bleeding refractory to platelet transfusions are also excluded from this study.
- Major surgery within 4 weeks of study enrollment.
- Are receiving warfarin (Coumadin).
- Females who are pregnant or breast feeding.
- Have known positive results of human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg) or hepatitis C antibodies (HCAb).
- Have received treatment within 28 days of the initial dose of study drug with an experimental agent for noncancerous indications that has not received regulatory approval for any indication.
- Participants receiving amiodarone, quinidine, propofol, or clozapine.
- Participants receiving treatment with strong or moderate inhibitors of cytochrome P450 (CYP)2C19, including proton-pump inhibitors (PPIs). Esomeprazole or pantoprazole are allowed if not administered within 72 hours before or after LY573636 administration
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Aurora, Colorado, 80045
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Baltimore, Maryland, 21287
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Houston, Texas, 77030
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Las Vegas, Nevada, 89135
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Los Angeles, California, 90095
About this study
Official title: Phase 1 Study of LY573636-sodium in Patients With Essential Thrombocythemia and Acute Myeloid Leukemia
The purpose of this study is to determine a safe dose of LY573636-sodium to be given to patients with acute myeloid leukemia and to determine any side effects that may be associated with LY573636-sodium in this patient population. Efficacy measures will also be used to assess the activity of LY573636-sodium in acute myeloid leukemia and essential thrombocythemia patients.
- Conditions
- Acute Myeloid Leukemia, Essential Thrombocythemia
- Being tested
- LY573636-sodium
- Keywords
- Acute Myeloid Leukemia, Myeloid Leukemia, Relapsed, Refractory
- Medical subject headings
- Leukemia, Myeloid, Acute, Thrombocythemia, Essential, Leukemia, Myeloid, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LY573636-sodiumDrug
Also called LY573636
Individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Dosing will be done on Day 1 of a 35-day cycle for acute myeloid leukemia (AML) and Day 1 of a 28-day cycle for essential thrombocythemia (ET) for at least one cycle. A participant may have additional cycles of LY573636 if he or she is receiving benefit from the study drug and does not fulfill any of the criteria for study discontinuation.
| Study group | Role | What they receive |
|---|---|---|
| LY573636 | Experimental | Not described Receives: Drug: LY573636-sodium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended Phase 2 Dose of LY573636-Sodium in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) and Essential Thrombocythemia (ET)
Recommended Phase 2 dose was determined by maximum tolerated dose (MTD). MTD is the highest dose at which no more than 1 of 6 participants experienced a dose-limiting toxicity (DLT) and level immediately below that which had ≥2 instances of DLT. A DLT is an adverse event (AE) observed during the first cycle of treatment that is believed to be related to LY573636 and fulfills any of the following: ET only , Common Terminology Criteria for AE (CTCAE, Version 3.0) Grade (Gr) 4 hematologic toxicity for ≥3 days; For all, ≥Gr 3 nonhematological toxicity except for nausea/vomiting or diarrhea unless it fits the next criteria; ≥Gr 3 nausea, vomiting, or diarrhea that persists >7 days despite maximal treatment; Gr 3 electrolyte disturbances that persist despite maximal measures; DLT can be declared if a participant experienced increasing toxicity during treatment. The primary outcome measure was not analyzed because the enrollment was stopped early before MTD was reached.
Measured: Predose up to 35 days postdose in Cycle 1
Secondary outcomes (3)
Pharmacokinetics Area Under the Curve(AUC) of LY573636 Above the Albumin-Corrected Threshold (AUCalb)
LY573636 has been found to be highly bound to albumin. AUCalb is a surrogate measure of exposure to unbound (free) LY573636.
PK sample is withdrawn at any time on days 8,14,15,21,28.
Measured: Predose,1h,2h,4h, 8d,14d,15d,21d,28d post dose
Number of Participants With Bone Marrow (BM) Response
The International Working Group's revised recommendations were used to assess response in acute myeloid leukemia (AML): complete response (CR) is <5% blasts in BM and with a cell count ≥200 cells in BM, and with peripheral blood platelets ≥100x10⁹/liter (L) and absolute neutrophils ≥1x10⁹/L; CR with incomplete blood count recovery is defined as CRi; partial response (PR) is ≥5% blasts in BM but with ≥50% reduction in blast count. Number of responders for AML = CR+PR+ CRi. Result of a European Leukemia Net consensus conference was used to assess response in essential thrombocythemia (ET). CR is platelets ≤400x10⁹/L in peripheral blood, no disease-related symptoms, normal spleen size and white blood cells ≤10x10⁹/L in peripheral blood; PR has platelets ≤600x10⁹/L in peripheral blood or decrease > 50% from baseline but does not meet CR criteria. Number of responders for ET = CR+PR.
Measured: Baseline to measured progressive disease up to 70 days
Pharmacokinetics: Concentration Maximum (Cmax) of LY573636
PK sample is withdrawn at any time on days 8,14,15,21,28.
Measured: Predose,1h,2h,4h, 8d,14d,15d,21d,28d post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2008 (estimated)
- Study startAug 2008
- Primary completionDec 2011
- Study completionDec 2011
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.
- More trials run by Eli Lilly and CompanyThe 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
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon -Fri 9AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00718159
- Sponsor's protocol ID
- 12266
- Other IDs
- H8K-MC-JZAJ
- Status last verified
- Dec 2018
- First submitted
- 16 Jul 2008
- Last updated
- 10 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of LY573636-sodium in Patients With Essential Thrombocythemia and Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT00718159
- Acronym / sponsor ID
- 12266
- Conditions
- Acute Myeloid Leukemia, Essential Thrombocythemia
- Keywords
- Acute Myeloid Leukemia, Myeloid Leukemia, Relapsed, Refractory
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- Aug 2008
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 18 Jul 2008 (estimated)
- Results
- Posted 16 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine a safe dose of LY573636-sodium to be given to patients with acute myeloid leukemia and to determine any side effects that may be associated with LY573636-sodium in this patient population. Efficacy measures will also be used to assess the activity of LY573636-sodium in acute myeloid leukemia and essential thrombocythemia patients.
Study design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LY573636 | Experimental | Drug: LY573636-sodium |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Participants who have a diagnosis of either essential thrombocythemia or acute myeloid leukemia that is relapsed or refractory to at least one prior standard treatment. If participants have acute promyelocytic leukemia, they must be resistant and/or intolerant of both all trans retinoic acid (ATRA) and arsenic trioxide.
- Are at least 18 years of age.
- Have given written informed consent approved by Lilly and the ethical review board (ERB)/institutional review board (IRB) governing the site.
- Must have adequate hepatic and renal function.
- Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, immunotherapy, cancer-related hormonal therapy, or other investigational therapy for at least 21 days for myelosuppressive agents (such as cytarabine, daunorubicin, and gemtuzumab ozogamicin) or 14 days for non-myelosuppressive agents prior to receiving study drug and recovered from the acute effects of therapy. Hydroxyurea used to control peripheral blood blast count is permitted within these respective periods, but it must be stopped at least 24 hours before study drug administration.
Key exclusion criteria (15 listed)
- Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of the initial dose of study drug for a non-myelosuppressive or myelosuppressive agent, respectively.
- Participants with myeloproliferative disorders (for example, chronic myeloid leukemia (CML), polycythemia vera and primary myelofibrosis) other than essential thrombocythemia.
- Have received an autologous or allogenic stem cell transplant within 75 days of the initial dose of study drug for the dose escalation phase or within 60 days of the initial dose of study drug for the dose confirmation phase. Recipients of an allogeneic stem cell transplant must have discontinued immunosuppressive therapy at least 24 hours before study drug administration with no more than Grade 1 acute graft-versus-host disease.
- Have previously completed or withdrawn from this study or any other study investigating LY573636 sodium.
- Have serious preexisting medical conditions that in the opinion of the investigator would preclude participation in this study.
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 |
|---|---|---|
| LY573636-sodiumAlso: LY573636Individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Dosing will be done on Day 1 of a 35-day cycle for acute myeloid leukemia (AML) and Day 1 of a 28-day cycle for essential thrombocythemia (ET) for at least one cycle. A participant may have additional cycles of LY573636 if he or she is receiving benefit from the study drug and does not fulfill any of the criteria for study discontinuation. | Drug | LY573636 |
Primary outcome
Recommended Phase 2 Dose of LY573636-Sodium in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) and Essential Thrombocythemia (ET)
Time frame: Predose up to 35 days postdose in Cycle 1
Recommended Phase 2 dose was determined by maximum tolerated dose (MTD). MTD is the highest dose at which no more than 1 of 6 participants experienced a dose-limiting toxicity (DLT) and level immediately below that which had ≥2 instances of DLT. A DLT is an adverse event (AE) observed during the first cycle of treatment that is believed to be related to LY573636 and fulfills any of the following: ET only , Common Terminology Criteria for AE (CTCAE, Version 3.0) Grade (Gr) 4 hematologic toxicity for ≥3 days; For all, ≥Gr 3 nonhematological toxicity except for nausea/vomiting or diarrhea unless it fits the next criteria; ≥Gr 3 nausea, vomiting, or diarrhea that persists >7 days despite maximal treatment; Gr 3 electrolyte disturbances that persist despite maximal measures; DLT can be declared if a participant experienced increasing toxicity during treatment. The primary outcome measure was not analyzed because the enrollment was stopped early before MTD was reached.
3 secondary outcomes
Pharmacokinetics Area Under the Curve(AUC) of LY573636 Above the Albumin-Corrected Threshold (AUCalb)
Time frame: Predose,1h,2h,4h, 8d,14d,15d,21d,28d post dose
Number of Participants With Bone Marrow (BM) Response
Time frame: Baseline to measured progressive disease up to 70 days
Pharmacokinetics: Concentration Maximum (Cmax) of LY573636
Time frame: Predose,1h,2h,4h, 8d,14d,15d,21d,28d post dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Lilly Clinical Trial RegistryLink provided by the sponsor.
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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.
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon -Fri 9AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) study director
Eli Lilly and Company
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LY573636-sodium in people with Acute Myeloid Leukemia and Essential Thrombocythemia, run by Eli Lilly and Company at 5 sites 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 8 inclusion and 15 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 10 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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?
Yes. Results are posted in the registry (first posted 16 Oct 2018). 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?
Recommended Phase 2 Dose of LY573636-Sodium in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) and Essential Thrombocythemia (ET) (time frame: Predose up to 35 days postdose in Cycle 1). 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 10 Jan 2019.