Details

Details

Title A Single Arm, Phase II study of Eltrombopag to Enhance Platelet Count Recovery in Elderly Patients with Acute Myeloid Leukemia undergoing Remission Induction therapy

IRB CASE4913

CC 14-147

Hospital Main Campus

Phase Phase 2

Disease Leukemia - Acute Myeloid (AML)

Drug Eltrombopag

Description

Description

Primary Objective
  • To determine whether eltrombopag leads to early platelet recovery in older AML patients (> 60 years) who attain morphologic remission on day 14 (range, day 14-17) bone marrow assessment following remission IC.
Secondary Objectives
  • To determine the effect of eltrombopag on megakaryopoiesis - median time to reach platelet count ≥ 50,000 /μL and ≥ 100,000 /μL, number of days of platelet transfusion, rates of platelet transfusion-independence and the median time to reach platelet transfusionindependence.
  • To determine the effect of eltrombopag on the rates of clinically significant bleeding events (CSBE) [Appendix I].
  • To determine the effect of eltrombopag on erythropoiesis the median time to red blood cell transfusion independence.
  • To determine the effect of eltrombopag on granulopoiesis-the time taken to reach an absolute neutrophil count of > 500 /μL.
  • To determine the safety and tolerability of eltrombopag in AML patients undergoing remission IC - incidence and severity of eltrombopag-related adverse events.
  • To determine the rates of CR, rates of CRp, time to attain CR, and time to initiation of postremission therapy.
Inclusion Criteria

Inclusion Criteria

  1. Patients must be > 60 years of age
  2. All categories of AML will be included except for acute promyelocytic leukemia (APL) [AML-M3 as defined by 1976 French-American-British (FAB) classification, or APL with t(15;17)(q22;q12); PML-RARA as defined by the revised 2008 World Health Organization (WHO) classification of myeloid neoplasms and acute leukemias], acute megakaryocytic leukemia [AML-M7 type as per FAB or AML (megakaryoblastic) with t(1;22)(p13;q13); RBM15-MKL1 as per WHO 2008 revised classification] and acute leukemias of ambiguous lineage (as per WHO 2008 revised classification)], undergoing 7 + 3 remission IC with cytarabine and an anthracycline (daunorubicin or idarubicin). All cases have to be histopathologically confirmed by a diagnostic bone marrow biopsy. Use of granulocyte colony-stimulating factor (G-CSF) for any indication must have been discontinued at least 7 days prior to entry into the study.
  3. Patients with secondary AML arising out of MDS (all subtypes under WHO classification), chronic myelomonocytic leukemia (CMML); therapy-related AML and those with a prior autologous hematopoietic cell transplantation are eligible.
  4. No morphological evidence of disease (defined as marrow myeloblast percentage of < 5%) on day 14 bone marrow examination (range, day 14-17; day 1 refers to the first day of IC) following remission IC.
  5. Must not be using greater than physiologic doses of a corticosteroid agent (dose equivalent to > 10mg/day of prednisone) within 28 days of the first day of the study drug.
  6. Must be able to give voluntary informed written consent to participate in the study. Informed consent will be obtained prior to starting remission IC (can be obtained even on the first day of remission IC if obtained before administration of chemotherapy) and before any studyrelated procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
  7. Male subject, even if surgically sterilized (ie, status post-vasectomy) must agree to one of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse.
  8. ECOG performance status of 0 to 2 (Appendix II).
Exclusion Criteria

Exclusion Criteria

  1. Any serious medical condition, laboratory abnormality, or psychiatric illness that, in the view of the treating physician, would place the participant at an unacceptable risk if he or she were to participate in the study or would prevent that person from giving informed consent.
  2. Prior malignancy in the 2 years before enrollment in the study (other than curatively treated carcinoma in-situ of the cervix or non-melanoma skin cancer).
  3. Secondary AML arising out of myeloproliferative neoplasms [as per the revised 2008 WHO classification of myeloid neoplasms and acute leukemias] and MDS/MPD neoplasms other than CMML [as per the revised 2008 WHO classification of myeloid neoplasms and acute leukemias]. Refractory Anemia with Ringed Sideroblasts with thrombocytosis (RARS-T) classified as MDS/MPN neoplasm, unclassifiable will be excluded. AML patients with presenting features suspicious of underlying unrecognized MPD such as marked splenomegaly (> 20 cm) and or platelet counts in excess of 100000/μL will be excluded. Patients with relapsed or refractory AML will be excluded.
  4. Radiation therapy, cytotoxic chemotherapy, and combined modality (both radiation and chemotherapy) used to treat other cancers or medical conditions and administered within 12 months prior to signing informed consent. Use of hydroxyurea or emergent leukapheresis (for cytoreduction of highly elevated white blood cell counts) is permissible. Those AML patients who initially receive treatment with all-trans retinoic acid (ATRA) for presumptive diagnosis of APL but if APL is ruled out in final pathology will be eligible for the study.
  5. Prior history of treatment with recombinant TPO or TPO-R agonists.
  6. History of arterial or venous thrombosis [excluding line-thrombosis] within the last 1 year, or those with known inherited coagulopathies. Arterial or venous thrombosis includes pulmonary embolism, deep vein thrombosis of both upper [excluding line-thrombosis] and lower extremities, coronary artery disease managed medically or requiring intervention (percutaneous stent placement or coronary bypass surgery), cerebrovascular accident (for transient ischemic attacks clinical documentation is required), or involvement of other organs (such as hepatic, renal, spleen or other sites).
  7. Any evidence of fibrosis on morphological examination of bone marrow at the time of AML diagnosis.
  8. Concomitant participation in any other investigational treatment study. Simultaneous participation in non-therapeutic or observational studies will not be an exclusion criterion.
  9. Uncontrolled intercurrent illness including, but not limited to uncontrolled infection, symptomatic or decompensated congestive heart failure, cardiac arrhythmia, unstable angina, cirrhosis or renal insufficiency (acute or chronic) on hemodialysis (at the time of diagnosis of AML).
  10. Liver enzymes (AST and ALT) > 2.5 times the upper limit of normal (ULN), and or total bilirubin > 1.5 x ULN.
  11. Serum creatinine > 1.5 x ULN.
  12. A known immediate or delayed hypersensitivity reaction or idiosyncrasy that, in the opinion of the Medical Monitor is due to drugs chemically related to eltrombopag or excipients (e.g. mannitol).
  13. Known history of HIV or active hepatitis B or C.
  14. No major surgery within 4 weeks prior to signing of informed consent.
  15. Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum b-human chorionic gonadotropin (b-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for postmenopausal or surgically sterilized women.