Acute Myeloid LeukemiaPhase 1/2PrE0901NCT01656252
Trial of Eltrombopag During Consolidation Therapy in Adults With AML in Complete Remission
A Phase 1/2 study testing Phase I- Cytarabine & Eltrombopag, Phase II- Sequence A and Phase II- Sequence B in people with Acute Myeloid Leukemia, run by PrECOG, LLC. at 5 sites in United States.
Trial summary
Patients with Acute Myeloid Leukemia (AML) in complete remission will receive eltrombopag while undergoing consolidation chemotherapy with high-dose cytarabine. Eltrombopag may help increase the number of platelets during chemotherapy and may help prevent the risk of bleeding. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Phase I- Cytarabine & Eltrombopag, Phase II- Sequence A and Phase II- Sequence B
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 5 sitesUnited States
- Study dates
- Jul 2012to Mar 2016
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Cytomorphologically documented diagnosis of acute myeloid leukemia (AML). Acute promyelocytic leukemia patients will be excluded (FAB M3). FAB classification, cytogenetics and molecular markers (if applicable) must be available at registration.
- Phase I Enrollment:
- Must be in first or second complete remission, e.g., no evidence of active disease in blood, bone marrow (<5% blasts), or other tissues.
- For each remission, may have received no more than 2 cycles of induction treatment (any type).
- May have received no more than one course of consolidation for the current remission prior to enrollment (any type)
- Phase II Enrollment:
Show all 42Show fewer
- Must be in first complete remission, e.g., no evidence of active disease in blood, bone marrow (<5% blasts), or other tissues.
- May have received no more than 2 cycles of induction treatment (any type).
- Enrollment in Either Phase:
- Remission status must be documented by a bone marrow examination up to 28 days prior to study registration.
- Have recovered from induction and first consolidation (if applicable) therapy side effects (or ≤grade 1).
- ≥18 years of age and ≤70 years of age.
- ECOG performance status 0, 1, 2.
- Have not received cytotoxic drug therapy within 21 days of registration.
- Have not received hematopoietic colony stimulating growth factors within 14 days of registration.
- Have not received packed red blood cells or platelets within 7 days of registration.
- Have not received investigational agents within 30 days of registration and will not receive any investigational agents other than eltrombopag/placebo during study.
- Signed IRB-approved informed consent.
- Willing to provide blood samples for research purposes.
- Adequate organ function obtained within 28 days prior to registration:
- Absolute neutrophil count >1 x 10⁹/L
- Platelet count >100 x 10⁹/L
- Total direct serum bilirubin ≤1.5x upper limit of normal (ULN)
- ALT and AST ≤3x ULN
- BUN and serum creatinine <2x ULN
- Albumin ≥2.5 g/dL
- PT and PTT 80-120% of institutional normal range
- Women of childbearing potential must have a negative serum pregnancy test within 14 days of registration.
- Not pregnant nor breast feeding.
- Women of childbearing potential and sexually active males must use an accepted and effective method of contraception.
- Patients of known East Asian ancestry (Chinese, Japanese, Taiwanese, and Korean) are excluded from protocol participation for safety and efficacy reasons.
- Able to swallow and retain orally administered medication.
- No clinically significant gastrointestinal abnormalities such as malabsorption syndrome or major resection of the stomach or bowels.
- No clinical evidence of hepatomegaly or splenomegaly.
- No known risk for Torsades de Pointes. (Eltrombopag use has not been shown to be associated with Torsades de Pointes.)
- No active or unresolved infection and must be off all antibiotics for at least 7 days prior to registration.
- No current evidence of invasive fungal infection.
- No known Hepatitis B, Hepatitis C active disease.
- No known Human Immunodeficiency Virus (HIV) seropositivity. The risk for potential toxicities secondary to HIV (e.g., increased risk for fatal opportunistic infection) may confound the toxicity profile of eltrombopag.
- Patients with a history of Central Nervous System (CNS) leukemia are eligible if there is documentation of no current CNS involvement on cerebrospinal fluid (CSF) examination (e.g., negative CSF by lumbar puncture) within 28 days of registration.
- No prior or concomitant malignancy in the past 5 years which is currently active and likely to interfere with the patient's treatment for AML or which is likely to increase the patient's morbidity or mortality. No prior chemotherapy or radiation therapy allowed (unless related to AML treatment).
- No concurrent organ damage or medical problems that would prohibit therapy.
Who cannot join
None listed.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University Hospitals Case Medical Center
Cleveland, Ohio, 44106
Penn State Hershey Cancer Institute
Hershey, Pennsylvania, 17033
Vanderbilt University
Nashville, Tennessee, 37232
Mayo Clinic, Rochester
Rochester, Minnesota, 55905
University of Massachusetts Worcester
Worcester, Massachusetts, 01655
About this study
Official title: Phase I Dose Finding/Phase II Placebo-Controlled Trial of Eltrombopag During Consolidation Therapy in Adults With Acute Myeloid Leukemia (AML) in Complete Remission
Patients with Acute Myeloid Leukemia (AML) in complete remission will receive eltrombopag while undergoing consolidation chemotherapy with high-dose cytarabine. Eltrombopag may help increase the number of platelets during chemotherapy and may help prevent the risk of bleeding.
Phase I will study the side effects, best dose and platelet effects of eltrombopag when given with consolidation chemotherapy. After the maximum safe and tolerated dose and schedule is found in Phase I, the study will proceed to Phase II. Phase II will confirm the dose and schedule of eltrombopag identified in Phase I that can increase platelet counts in patients receiving consolidation therapy.
Read the detailed description
Consolidation chemotherapy with high dose cytarabine usually causes myelosuppression for 14 to 21 days after each treatment. Patients have low blood counts for days or weeks before the bone marrow resumes function. This may result in e.g., hospitalization, treatment with antibiotics, and transfusions with blood and/or platelets. In addition, this may cause a delay in treatment and reduction in dose. To achieve the best outcome from treatment, dose reductions and delays in treatment must be avoided.
The incidence and duration of decreased white blood cells (neutropenia) and neutropenic complications have been reduced by the use of growth colony stimulating factors. Additionally, the use of erythropoietin-stimulating factors has reduced anemia and the need for red blood cell transfusions. Thrombocytopenia remains an important limiting factor in administration of chemotherapy and maintaining dose intensity in some patients. Additionally, the risk of bleeding secondary to low platelet counts may increase sickness or even death in patients undergoing cancer treatment.
Thrombopoietin (TPO) is the principal cytokine involved in the regulation of megakaryopoiesis and platelet production. Eltrombopag is an orally bioavailable, small molecule, TPO-receptor agonist that stimulates platelet production by a similar, but not identical, mechanism to endogenous TPO. Eltrombopag has been approved in the U.S. for the treatment of chronic Idiopathic Thrombocytopenic Purpura. Eltrombopag is also under development for other indications such as Hepatitis C Virus-associated thrombocytopenia, Myelodysplastic Syndrome/AML, and oncology related thrombocytopenias. This agent appears to possess many of the desirable properties for a treatment for chemotherapy induced thrombocytopenia, including oral administration.
The Phase I portion of this study will be conducted using a dose escalation/de-escalation strategy for patients in either the first or second complete remission. Dose escalations are planned in the form of both acceleration of date of initiation of eltrombopag relative to the start of consolidation chemotherapy as well as increasing daily dosing.
The Phase II portion will be conducted using the dose and schedule selected from the Phase I portion of the study for those patients in first complete remission. Patients will be used as their own controls, e.g., a two-period two-treatment cross-over design. Patients will be randomly allocated 1:1 to one of two sequences. Patients randomized to Sequence A will receive eltrombopag with their first cycle of consolidation and placebo with Cycle 2. Patients randomized to Sequence B will receive placebo with their first cycle of consolidation and eltrombopag with Cycle 2. The treatment assignment will be blinded to the patient and all study/sponsor personnel.
Patients will undergo blood sample collection for Thrombopoietin(TPO)/ Erythropoietin(EPO) and pharmacokinetic analysis of eltrombopag in Phase I and pharmacokinetic analysis of eltrombopag in the Phase II portion of the study.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Phase I- Cytarabine & Eltrombopag, Phase II- Sequence A, Phase II- Sequence B
- Keywords
- Acute Leukemia, Complete Remission, Consolidation, Consolidation Chemotherapy, Cytarabine, Eltrombopag, Leukemia, Thrombocytopenia, Thrombopoietin
- Medical subject headings
- Leukemia, Myeloid, Acute, Pathologic Complete Response, Leukemia, Thrombocytopenia, Jacobs syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Phase I- Cytarabine & EltrombopagDrug
Also called Ara-C, Cytosar-U, Cytosine Arabinoside, Promacta
Cycle 1= Cytarabine 3 g/m² IV twice daily on Days 1, 3 and 5 (Patients >60 years of age will receive cytarabine 1.5 g/m² IV per dose). Day 1 must start in AM.
Eltrombopag (Open-Label) by mouth daily until platelet recovery or for 35 consecutive days, whichever occurs first. Phase I will determine the dose and schedule of Eltrombopag to be used in Phase II.
One cycle of consolidation therapy with high-dose cytarabine and eltrombopag will be received on study. Additional chemotherapy may be administered at the investigators discretion without eltrombopag.
Phase II- Sequence ADrug
Also called Ara-C, Cytosar-U, Cytosine Arabinoside, Promacta
Cytarabine 3 g/m² IV twice daily on Days 1, 3 and 5 (Patients >60 years of age will receive cytarabine 1.5 g/m² IV per dose). Day 1 must start in AM.
Eltrombopag by mouth daily (dose and schedule as determined in Phase I) with 1st cycle of high-dose consolidation chemotherapy and placebo by mouth daily with 2nd cycle.
Eltrombopag/placebo will continue until platelet recovery or for 35 consecutive days, whichever occurs first.
Additional chemotherapy may be administered at the investigators discretion without eltrombopag.
Phase II- Sequence BDrug
Also called Ara-C, Cytosar-U, Cytosine Arabinoside, Promacta
Cytarabine 3 g/m² IV twice daily on Days 1, 3 and 5 (Patients >60 years of age will receive cytarabine 1.5 g/m² IV per dose). Day 1 must start in AM.
Placebo by mouth daily with 1st cycle of high-dose consolidation therapy and Eltrombopag by mouth daily (dose and schedule as determined in Phase I) with 2nd cycle.
Eltrombopag/placebo will continue until platelet recovery or for 35 consecutive days, whichever occurs first.
Additional chemotherapy may be administered at the investigators discretion without eltrombopag.
| Study group | Role | What they receive |
|---|---|---|
| Phase I- Cytarabine & Eltrombopag | Experimental | Cycle 1= Cytarabine twice daily on Days 1, 3 and 5 and Eltrombopag (Open-Label) until platelet recovery or for 35 consecutive days, whichever occurs first. Phase I will determine the dose and schedule of Eltrombopag to be used in Phase II. Receives: Drug: Phase I- Cytarabine & Eltrombopag |
| Phase II- Sequence A | Experimental | Cytarabine twice daily on Days 1, 3 and 5. Eltrombopag(dose and schedule as determined in Phase I) with 1st cycle of high-dose consolidation chemotherapy and placebo with 2nd cycle. Treatment sequence will be blinded to the patient and all study/sponsor personnel. Receives: Drug: Phase II- Sequence A |
| Phase II- Sequence B | Experimental | Cytarabine twice daily on Days 1, 3 and 5. Placebo with 1st cycle of high-dose consolidation therapy and Eltrombopag(dose and schedule as determined in Phase I) with 2nd cycle. Treatment sequence will be blinded to the patient and all study/sponsor personnel. Receives: Drug: Phase II- Sequence B |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I- Optimal Tolerated Dose of Eltrombopag
To determine the safety, tolerability and optimal dose of eltrombopag in acute myeloid leukemia patients in complete remission receiving intensive consolidation chemotherapy. The optimal dose was based on rules involving observation of Dose Limiting Toxicity (DLT events), defined as a CTCAE Version 4 non-hematologic adverse event of grade 3 or higher occurring within 30 days of the last dose of eltrombopag judged by the investigator to be at least possibly related to eltrombopag administration.
Measured: 13 months
Phase I - Dose Level With Best Kinetics of Platelet Count Recovery
To describe the kinetics of platelet count recovery in acute myeloid leukemia patients in complete remission receiving intensive consolidation chemotherapy who will be receiving eltrombopag. This is assessed graphically by plotting platelet count vs. days relative to start of cytarabine for each patient.
Measured: 13 months
Phase II- Assess if Platelet Count Recovery is Increased With Eltrombopag
To determine if platelet recovery following consolidation chemotherapy is accelerated with eltrombopag.
Measured: 62 months
Secondary outcomes (8)
Phase I & Phase II- Pharmacokinetics of Eltrombopag
To determine the plasma concentrations of eltrombopag in acute myeloid leukemia patients in complete remission receiving intensive consolidation chemotherapy (selected dosing regimen only).
Measured: 62 months
Phase II- Platelet Transfusion Requirements
To determine the impact of eltrombopag on platelet transfusion requirements in the setting of consolidation chemotherapy.
Measured: 62 months
Phase II- Red Blood Cell Transfusion Requirements
To determine the impact of eltrombopag on red blood cell transfusion requirements.
Measured: 62 months
Phase II- Bleeding Event Occurrence
To determine the impact of eltrombopag on occurrence of bleeding events.
Measured: 62 months
Phase II- Time to Platelet Count Recovery
To determine the impact of eltrombopag on time to platelet recovery following consolidation chemotherapy.
Measured: 62 months
Phase II- Depth of Platelet Nadir
To determine the impact of eltrombopag on the depth of platelet nadir following a cycle of consolidation chemotherapy.
Measured: 62 months
Phase II- Duration of Platelet Nadir
To determine the duration of platelet nadir in the setting of eltrombopag exposure.
Measured: 62 months
Phase II- Safety of Eltrombopag With Consolidation
To determine the safety and tolerability of eltrombopag when given at the optimal dose in the setting of consolidation chemotherapy.
Measured: 62 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2012 (estimated)
- Study startJul 2012
- Primary completionMar 2016
- Study completionMar 2016
Why it stopped: Study stopped per Novartis request due to futility from another study.
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 (5)Papers the sponsor has linked to this study.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- PrECOG, LLC.
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline, Novartis
- Responsible party
- Sponsor
- Investigators
- Hillard M Lazarus, MD, Study chair, University Hospitals Cleveland Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01656252
- Sponsor's protocol ID
- PrE0901
- Other IDs
- ELT114465
- Acronym
- PrE0901
- Status last verified
- Oct 2020
- First submitted
- 31 Jul 2012
- Last updated
- 3 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: Data is proprietary.
Publications
Mavroudi I, Pyrovolaki K, Pavlaki K, Kozana A, Psyllaki M, Kalpadakis C, Pontikoglou C, Papadaki HA. Effect of the nonpeptide thrombopoietin receptor agonist eltrombopag on megakaryopoiesis of patients with lower risk myelodysplastic syndrome. Leuk Res. 2011 Mar;35(3):323-8. doi: 10.1016/j.leukres.2010.06.029. Epub 2010 Aug 4.
PubMed 20688394Will B, Kawahara M, Luciano JP, Bruns I, Parekh S, Erickson-Miller CL, Aivado MA, Verma A, Steidl U. Effect of the nonpeptide thrombopoietin receptor agonist Eltrombopag on bone marrow cells from patients with acute myeloid leukemia and myelodysplastic syndrome. Blood. 2009 Oct 29;114(18):3899-908. doi: 10.1182/blood-2009-04-219493. Epub 2009 Aug 26.
PubMed 19710504Kellum A, Jagiello-Gruszfeld A, Bondarenko IN, Patwardhan R, Messam C, Mostafa Kamel Y. A randomized, double-blind, placebo-controlled, dose ranging study to assess the efficacy and safety of eltrombopag in patients receiving carboplatin/paclitaxel for advanced solid tumors. Curr Med Res Opin. 2010 Oct;26(10):2339-46. doi: 10.1185/03007995.2010.510051.
PubMed 20735290Vadhan-Raj S. Management of chemotherapy-induced thrombocytopenia: current status of thrombopoietic agents. Semin Hematol. 2009 Jan;46(1 Suppl 2):S26-32. doi: 10.1053/j.seminhematol.2008.12.007.
PubMed 19245931Strickland SA, Wang XV, Cerny J, Rowe JM, Rybka W, Tallman MS, Litzow M, Lazarus HM. A novel PrECOG (PrE0901) dose-escalation trial using eltrombopag: enhanced platelet recovery during consolidation therapy in acute myeloid leukemia. Leuk Lymphoma. 2020 Sep;61(9):2191-2199. doi: 10.1080/10428194.2020.1762878. Epub 2020 May 30.
PubMed 32476546
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Dose Finding/Phase II Placebo-Controlled Trial of Eltrombopag During Consolidation Therapy in Adults With Acute Myeloid Leukemia (AML) in Complete Remission
- ClinicalTrials.gov ID
- NCT01656252
- Acronym / sponsor ID
- PrE0901 / PrE0901
- Conditions
- Acute Myeloid Leukemia
- Keywords
- Acute Leukemia, Complete Remission, Consolidation, Consolidation Chemotherapy, Cytarabine, Eltrombopag, Leukemia, Thrombocytopenia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study stopped per Novartis request due to futility from another study.
- Enrolment
- 15 participants (actual)
- Lead sponsor
- PrECOG, LLC.University, hospital or other
- Collaborators
- GlaxoSmithKline, Novartis
- Study start
- Jul 2012
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 2 Aug 2012 (estimated)
- Results
- Posted 28 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with Acute Myeloid Leukemia (AML) in complete remission will receive eltrombopag while undergoing consolidation chemotherapy with high-dose cytarabine. Eltrombopag may help increase the number of platelets during chemotherapy and may help prevent the risk of bleeding.
Phase I will study the side effects, best dose and platelet effects of eltrombopag when given with consolidation chemotherapy. After the maximum safe and tolerated dose and schedule is found in Phase I, the study will proceed to Phase II. Phase II will confirm the dose and schedule of eltrombopag identified in Phase I that can increase platelet counts in patients receiving consolidation therapy.
Detailed description
Consolidation chemotherapy with high dose cytarabine usually causes myelosuppression for 14 to 21 days after each treatment. Patients have low blood counts for days or weeks before the bone marrow resumes function. This may result in e.g., hospitalization, treatment with antibiotics, and transfusions with blood and/or platelets. In addition, this may cause a delay in treatment and reduction in dose. To achieve the best outcome from treatment, dose reductions and delays in treatment must be avoided.
The incidence and duration of decreased white blood cells (neutropenia) and neutropenic complications have been reduced by the use of growth colony stimulating factors. Additionally, the use of erythropoietin-stimulating factors has reduced anemia and the need for red blood cell transfusions. Thrombocytopenia remains an important limiting factor in administration of chemotherapy and maintaining dose intensity in some patients. Additionally, the risk of bleeding secondary to low platelet counts may increase sickness or even death in patients undergoing cancer treatment.
Thrombopoietin (TPO) is the principal cytokine involved in the regulation of megakaryopoiesis and platelet production. Eltrombopag is an orally bioavailable, small molecule, TPO-receptor agonist that stimulates platelet production by a similar, but not identical, mechanism to endogenous TPO. Eltrombopag has been approved in the U.S. for the treatment of chronic Idiopathic Thrombocytopenic Purpura. Eltrombopag is also under development for other indications such as Hepatitis C Virus-associated thrombocytopenia, Myelodysplastic Syndrome/AML, and oncology related thrombocytopenias. This agent appears to possess many of the desirable properties for a treatment for chemotherapy induced thrombocytopenia, including oral administration.
The Phase I portion of this study will be conducted using a dose escalation/de-escalation strategy for patients in either the first or second complete remission. Dose escalations are planned in the form of both acceleration of date of initiation of eltrombopag relative to the start of consolidation chemotherapy as well as increasing daily dosing.
The Phase II portion will be conducted using the dose and schedule selected from the Phase I portion of the study for those patients in first complete remission. Patients will be used as their own controls, e.g., a two-period two-treatment cross-over design. Patients will be randomly allocated 1:1 to one of two sequences. Patients randomized to Sequence A will receive eltrombopag with their first cycle of consolidation and placebo with Cycle 2. Patients randomized to Sequence B will receive placebo with their first cycle of consolidation and eltrombopag with Cycle 2. The treatment assignment will be blinded to the patient and all study/sponsor personnel.
Patients will undergo blood sample collection for Thrombopoietin(TPO)/ Erythropoietin(EPO) and pharmacokinetic analysis of eltrombopag in Phase I and pharmacokinetic analysis of eltrombopag in the Phase II portion of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Phase I- Cytarabine & Eltrombopag | Experimental | Drug: Phase I- Cytarabine & EltrombopagCycle 1= Cytarabine twice daily on Days 1, 3 and 5 and Eltrombopag (Open-Label) until platelet recovery or for 35 consecutive days, whichever occurs first. Phase I will determine the dose and schedule of Eltrombopag to be used in Phase II. |
| Phase II- Sequence A | Experimental | Drug: Phase II- Sequence ACytarabine twice daily on Days 1, 3 and 5. Eltrombopag(dose and schedule as determined in Phase I) with 1st cycle of high-dose consolidation chemotherapy and placebo with 2nd cycle. Treatment sequence will be blinded to the patient and all study/sponsor personnel. |
| Phase II- Sequence B | Experimental | Drug: Phase II- Sequence BCytarabine twice daily on Days 1, 3 and 5. Placebo with 1st cycle of high-dose consolidation therapy and Eltrombopag(dose and schedule as determined in Phase I) with 2nd cycle. Treatment sequence will be blinded to the patient and all study/sponsor personnel. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (42 listed)
- Cytomorphologically documented diagnosis of acute myeloid leukemia (AML). Acute promyelocytic leukemia patients will be excluded (FAB M3). FAB classification, cytogenetics and molecular markers (if applicable) must be available at registration.
- Must be in first or second complete remission, e.g., no evidence of active disease in blood, bone marrow (<5% blasts), or other tissues.
- For each remission, may have received no more than 2 cycles of induction treatment (any type).
- May have received no more than one course of consolidation for the current remission prior to enrollment (any type)
- Must be in first complete remission, e.g., no evidence of active disease in blood, bone marrow (<5% blasts), or other tissues.
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Phase I- Cytarabine & EltrombopagAlso: Ara-C, Cytosar-U, Cytosine Arabinoside, PromactaCycle 1= Cytarabine 3 g/m² IV twice daily on Days 1, 3 and 5 (Patients >60 years of age will receive cytarabine 1.5 g/m² IV per dose). Day 1 must start in AM. Eltrombopag (Open-Label) by mouth daily until platelet recovery or for 35 consecutive days, whichever occurs first. Phase I will determine the dose and schedule of Eltrombopag to be used in Phase II. One cycle of consolidation therapy with high-dose cytarabine and eltrombopag will be received on study. Additional chemotherapy may be administered at the investigators discretion without eltrombopag. | Drug | Phase I- Cytarabine & Eltrombopag |
| Phase II- Sequence AAlso: Ara-C, Cytosar-U, Cytosine Arabinoside, PromactaCytarabine 3 g/m² IV twice daily on Days 1, 3 and 5 (Patients >60 years of age will receive cytarabine 1.5 g/m² IV per dose). Day 1 must start in AM. Eltrombopag by mouth daily (dose and schedule as determined in Phase I) with 1st cycle of high-dose consolidation chemotherapy and placebo by mouth daily with 2nd cycle. Eltrombopag/placebo will continue until platelet recovery or for 35 consecutive days, whichever occurs first. Additional chemotherapy may be administered at the investigators discretion without eltrombopag. | Drug | Phase II- Sequence A |
| Phase II- Sequence BAlso: Ara-C, Cytosar-U, Cytosine Arabinoside, PromactaCytarabine 3 g/m² IV twice daily on Days 1, 3 and 5 (Patients >60 years of age will receive cytarabine 1.5 g/m² IV per dose). Day 1 must start in AM. Placebo by mouth daily with 1st cycle of high-dose consolidation therapy and Eltrombopag by mouth daily (dose and schedule as determined in Phase I) with 2nd cycle. Eltrombopag/placebo will continue until platelet recovery or for 35 consecutive days, whichever occurs first. Additional chemotherapy may be administered at the investigators discretion without eltrombopag. | Drug | Phase II- Sequence B |
Primary outcome
Phase I- Optimal Tolerated Dose of Eltrombopag
Time frame: 13 months
To determine the safety, tolerability and optimal dose of eltrombopag in acute myeloid leukemia patients in complete remission receiving intensive consolidation chemotherapy. The optimal dose was based on rules involving observation of Dose Limiting Toxicity (DLT events), defined as a CTCAE Version 4 non-hematologic adverse event of grade 3 or higher occurring within 30 days of the last dose of eltrombopag judged by the investigator to be at least possibly related to eltrombopag administration.
Phase I - Dose Level With Best Kinetics of Platelet Count Recovery
Time frame: 13 months
To describe the kinetics of platelet count recovery in acute myeloid leukemia patients in complete remission receiving intensive consolidation chemotherapy who will be receiving eltrombopag. This is assessed graphically by plotting platelet count vs. days relative to start of cytarabine for each patient.
Phase II- Assess if Platelet Count Recovery is Increased With Eltrombopag
Time frame: 62 months
To determine if platelet recovery following consolidation chemotherapy is accelerated with eltrombopag.
8 secondary outcomes
Phase I & Phase II- Pharmacokinetics of Eltrombopag
Time frame: 62 months
Phase II- Platelet Transfusion Requirements
Time frame: 62 months
Phase II- Red Blood Cell Transfusion Requirements
Time frame: 62 months
Phase II- Bleeding Event Occurrence
Time frame: 62 months
Phase II- Time to Platelet Count Recovery
Time frame: 62 months
Phase II- Depth of Platelet Nadir
Time frame: 62 months
Phase II- Duration of Platelet Nadir
Time frame: 62 months
Phase II- Safety of Eltrombopag With Consolidation
Time frame: 62 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20688394Mavroudi I, Pyrovolaki K, Pavlaki K, Kozana A, Psyllaki M, Kalpadakis C, Pontikoglou C, Papadaki HA. Effect of the nonpeptide thrombopoietin receptor agonist eltrombopag on megakaryopoiesis of patients with lower risk myelodysplastic syndrome. Leuk Res. 2011 Mar;35(3):323-8. doi: 10.1016/j.leukres.2010.06.029. Epub 2010 Aug 4.
- Background: PubMed 19710504Will B, Kawahara M, Luciano JP, Bruns I, Parekh S, Erickson-Miller CL, Aivado MA, Verma A, Steidl U. Effect of the nonpeptide thrombopoietin receptor agonist Eltrombopag on bone marrow cells from patients with acute myeloid leukemia and myelodysplastic syndrome. Blood. 2009 Oct 29;114(18):3899-908. doi: 10.1182/blood-2009-04-219493. Epub 2009 Aug 26.
- Background: PubMed 20735290Kellum A, Jagiello-Gruszfeld A, Bondarenko IN, Patwardhan R, Messam C, Mostafa Kamel Y. A randomized, double-blind, placebo-controlled, dose ranging study to assess the efficacy and safety of eltrombopag in patients receiving carboplatin/paclitaxel for advanced solid tumors. Curr Med Res Opin. 2010 Oct;26(10):2339-46. doi: 10.1185/03007995.2010.510051.
- Background: PubMed 19245931Vadhan-Raj S. Management of chemotherapy-induced thrombocytopenia: current status of thrombopoietic agents. Semin Hematol. 2009 Jan;46(1 Suppl 2):S26-32. doi: 10.1053/j.seminhematol.2008.12.007.
- Results publication: PubMed 32476546Strickland SA, Wang XV, Cerny J, Rowe JM, Rybka W, Tallman MS, Litzow M, Lazarus HM. A novel PrECOG (PrE0901) dose-escalation trial using eltrombopag: enhanced platelet recovery during consolidation therapy in acute myeloid leukemia. Leuk Lymphoma. 2020 Sep;61(9):2191-2199. doi: 10.1080/10428194.2020.1762878. Epub 2020 May 30.
- Individual participant dataSharing planned: No. Data is proprietary.
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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.
Hillard M Lazarus, MD study chair
University Hospitals Cleveland Medical Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Phase I- Cytarabine & Eltrombopag, Phase II- Sequence A and Phase II- Sequence B in people with Acute Myeloid Leukemia, run by PrECOG, LLC. 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 42 inclusion and 0 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 3 Nov 2020. 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 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 28 Jun 2017). 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?
Phase I- Optimal Tolerated Dose of Eltrombopag (time frame: 13 months). The study lists 3 primary outcomes in all. 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 NCT01656252, which also lists 5 linked publications.
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 3 Nov 2020.