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. 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. 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. This agent appears to possess many of the desirable properties for a treatment for chemotherapy induced thrombocytopenia, including oral administration.
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. Patients will be randomly allocated 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. Day 1 must start in AM. Eltrombopag Open-Label by mouth daily until platelet recovery or for 35 consecutive days, whichever occurs first.
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. 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. 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.
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Acute promyelocytic leukemia patients will be excluded FAB M3. FAB classification, cytogenetics and molecular markers if applicable must be available at registration. Adequate organ function obtained within 28 days prior to registration:.
Try the modernized ClinicalTrials. Learn more about the modernization effort. Hide glossary Glossary Study record managers: refer to the Data Element Definitions if submitting registration or results information. Search for terms. Save this study. Warning You have reached the maximum number of saved studies TSQM-9 will be used to assess treatment satisfaction with medication.
The three scales of the TSQM-9 include the effectiveness scale, convenience scale, and global satisfaction scale. Eligibility Criteria.
Information from the National Library of Medicine Choosing to participate in a study is an important personal decision. Contacts and Locations.
Information from the National Library of Medicine To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor. Please refer to this study by its ClinicalTrials. More Information. National Library of Medicine U. National Institutes of Health U. Department of Health and Human Services.
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Drug: eltrombopag. Phase 2. Study Type :. Interventional Clinical Trial. Pregnant or lactating women. Subjects with liver enzymes 5x upper limit of normal or liver cirrhosis as determined by the investigator.
Patients with known history of HIV positivity. Patient with known active or uncontrolled infections not responding to appropriate therapy. Note: parallel enrollment in a disease registry is permitted. Known thrombophilic risk factors or history of thromboembolic disease. Exception: Subjects for whom the potential benefits of participating in the study outweigh the potential risks of thromboembolic events, as determined by the investigator.
Known immediate or delayed hypersensitivity reaction to eltrombopag or its excipient. Basic contraception methods include: Total abstinence when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence e. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment Male sterilization at least 6 months prior to screening.
The vasectomized male partner should be the sole partner for that subject. Barrier methods of contraception: Condom or Occlusive cap. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.
Female subjects who are nursing or pregnant positive serum or urine B-human chorionic gonadotrophin B-hCG pregnancy test at screening or pre-dose on Day 1. A condom is required to be used also by vasectomized men as well as during intercourse with a male partner in order to prevent delivery of the drug via semen.
Any condition that would prohibit the understanding or rendering of informed consent. Any condition that in the opinion of the investigator would interfere with the patient's safety or compliance on trial. Severe infection within 4 weeks prior to enrollment that in the opinion of the investigator would interfere with patient safety or compliance on trial.
Contacts and Locations. Information from the National Library of Medicine To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor. Please refer to this study by its ClinicalTrials. More Information. Upfront eltrombopag monotherapy induces stable hematologic remission in pediatric patients with nonsevere idiopathic aplastic anemia.
Pediatr Blood Cancer. Epub Jun N Engl J Med. Romiplostim Treatment of Chemotherapy-Induced Thrombocytopenia. J Clin Oncol. Epub Sep J Pediatr Hematol Oncol. Reduced proliferation of non-megakaryocytic acute myelogenous leukemia and other leukemia and lymphoma cell lines in response to eltrombopag.
Leuk Res. Epub Mar 3. Stem Cell Res. Epub May Thrombopoietin is essential for the maintenance of normal hematopoiesis in humans: development of aplastic anemia in patients with congenital amegakaryocytic thrombocytopenia. Ann N Y Acad Sci. In vitro megakaryocytopoietic and thrombopoietic activity of c-mpl ligand TPO on purified murine hematopoietic stem cells.
Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells. Cell Stem Cell. Epub Nov
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