Eltrombopag Olamine in Improving Platelet Recovery in Older Patients With Acute Myeloid Leukemia Undergoing Chemotherapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2016 by Case Comprehensive Cancer Center
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT02071901
First received: February 24, 2014
Last updated: February 17, 2016
Last verified: February 2016
  Purpose
This phase II trial studies how well eltrombopag olamine works in improving the recovery of platelet counts in older patients with acute myeloid leukemia undergoing induction (the first treatment given for a disease) chemotherapy. Platelet counts recover more slowly in older patients, leading to risk of complications and the delay of post-remission therapy. Eltrombopag olamine may cause the body to make platelets after chemotherapy.

Condition Intervention Phase
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
Adult Acute Basophilic Leukemia
Adult Acute Eosinophilic Leukemia
Adult Acute Megakaryoblastic Leukemia (M7)
Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
Adult Acute Monoblastic Leukemia (M5a)
Adult Acute Monocytic Leukemia (M5b)
Adult Acute Myeloblastic Leukemia With Maturation (M2)
Adult Acute Myeloblastic Leukemia Without Maturation (M1)
Adult Acute Myeloid Leukemia in Remission
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Adult Acute Myelomonocytic Leukemia (M4)
Adult Erythroleukemia (M6a)
Adult Pure Erythroid Leukemia (M6b)
Secondary Acute Myeloid Leukemia
Drug: eltrombopag olamine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official 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

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Patients with a median platelet count >= 50,000/uL [ Time Frame: Day 24 of Treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Median time needed to reach platelet count >= 50,000 /µL [ Time Frame: up to 12 weeks ] [ Designated as safety issue: No ]
    Defined as the average number of days from the first day of eltrombopag until the first of five consecutive days with platelet counts >= 50,000 /µL without a platelet transfusion. The time will be summarized using the Kaplan-Meier method and will use the logrank test and proportional hazards models.

  • Number of days of platelet transfusions [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    Defined as the average number of days from the first day of eltrombopag until the patient stopped treatment. The time will be summarized using the Kaplan-Meier method and will use the log-rank test and proportional hazards models.

  • Rates of clinically significant bleeding events [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: Yes ]
    The number of bleeding events experienced by patients during treatment including hematuria, gastrointestinal bleed (with or without requiring intervention, retroperitoneal bleeding, intra-cranial bleed, epistaxis not controlled by conservative measures and muscle or soft tissue hematomas.

  • Median time of absolute neutrophil recovery, defined as > 500/uL [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    The average number of days patients take to reach a neutrophil count >500/ul as summarized using the Kaplan-Meier method and modeled using logrank test and proportional hazards.

  • Median rise in hemoglobin level in patients with pretreatment hemoglobin of < 8 g/dL [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    The median increase in hemoglobin levels in g/dL among patients with a starting hemoglobin level <8g/dL

  • Complete Response rate [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    Complete Response rate is defined as the number of patients with a sustained improvement of platelet counts (independent of platelet transfusions) to ≥ 50,000 /µL lasting for at least 2 weeks.

  • Time to attain Complete Response [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    The average number of days patients take to achieve a complete response as defined as a sustained improvement of platelet counts (independent of platelet transfusions) to ≥ 50,000 /µL lasting for at least 2 weeks. This measurement will be summarized using the Kaplan-Meier method and will use the logrank test and proportional hazards models.

  • Partial Complete Response rate [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    Partial complete response rate is defined as the number of patients with a sustained improvement of platelet counts (independent of platelet transfusions) seen by at least a doubling of platelet count from the pretreatment thrombocytopenic level (defined as < 10000 /µL, ) or an absolute increase in platelet counts to between 30000 /µL and 50000 /µL, whichever is higher but not achieving complete response. Or if there is a need to restart eltrombopag due to drop in platelet count to below 50000 /µL following interruption of eltrombopag therapy after achieving platelet counts of > 100000 /µL on the drug.

  • Time to initiation of post-remission therapy [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    The average number of days from the the beginning of treatment to the onset of post-remission therapy as summarized using the Kaplan-Meier method and calculated using the logrank test and proportional hazards models.

  • Rate of refractory or persistent disease [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    The number of patients without complete or partial response to treatment

  • Overall Survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Survival is defined as the number of days from the day of study registration until the last follow-up or death

  • Incidence of adverse events, determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 4 weeks after last dose of eltrombopag olamine ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 31
Study Start Date: August 2014
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Supportive care (eltrombopag olamine)
Patients receive eltrombopag olamine PO QD until platelet counts reach >= 50,000/uL or for 8 weeks, whichever comes earlier. Treatment continues in the absence of unacceptable toxicity.
Drug: eltrombopag olamine
Given PO
Other Names:
  • Promacta
  • SB 497115
  • SB-497115
  • SB497115

Detailed Description:

PRIMARY OBJECTIVES:

I.To determine whether eltrombopag leads to early platelet recovery in older AML patients (≥ 60years) who attain morphologic remission on day 14 (range, day 14-17) bone marrow assessment following remission induction chemotherapy (IC).

SECONDARY OBJECTIVES:

I. 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 transfusion independence.

II. To determine the effect of eltrombopag on the rates of clinically significant bleeding events (CSBE).

III. To determine the effect of eltrombopag on erythropoiesis the median time to red blood cell transfusion independence.

IV. To determine the effect of eltrombopag on granulopoiesis- the time taken to reach an absolute neutrophil count of ≥ 500 /μL. V. To determine the safety and tolerability of eltrombopag in AML patients undergoing remission IC - incidence and severity of eltrombopag-related adverse events. VI. To determine rates of complete remission (CR), rates of partial complete remission (CRp), time to attain CR, and time to initiation of postremission consolidation therapy.

OUTLINE:

Patients receive eltrombopag olamine orally (PO) once daily (QD) until platelet counts reach ≥50,000/uL or for 8 weeks, whichever comes earlier. Treatment continues in the absence of unacceptable toxicity.

After completion of study treatment, patients are followed up for 2 years.

  Eligibility

Ages Eligible for Study:   60 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All categories of acute leukemia under the World Health Organization (WHO) 2008 classification except for acute promyelocytic leukemia (APL) and acute megakaryocytic leukemia, undergoing 7 + 3 IC with cytarabine and an anthracycline (daunorubicin or idarubicin or mitoxantrone); 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
  • No morphological evidence of disease on day 14 bone marrow examination following IC
  • Must not be using greater than physiologic doses of a corticosteroid agent (dose equivalent to > 10 mg/day of prednisone) within 28 days of the first day of treatment
  • Must be able to give voluntary informed written consent to participate in the study; informed consent will be obtained prior to initiation of remission IC and before any study-related 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
  • 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
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3
  • Patients with secondary AML arising out of MDS (all subtypes under WHO classification), chronic myelomonocytic leukemia (CMML); therapy-related AML and those patients with a prior autologous hematopoietic cell transplant are eligible

Exclusion Criteria:

  • 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
  • Prior malignancy in the 2 years before treatment in this study (other than curatively treated carcinoma in-situ of the cervix or non-melanoma skin cancer)
  • 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.
  • 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.
  • Prior history of treatment with recombinant thrombopoietin (TPO) or TPO-receptor (R) agonists
  • 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).
  • Evidence of fibrosis on bone marrow examination at the time of diagnosis
  • Active participation in any other investigational treatment study
  • Uncontrolled intercurrent illness including, but not limited to uncontrolled infection, symptomatic congestive heart failure, cardiac arrhythmia, unstable angina or renal insufficiency (acute or chronic) on hemodialysis
  • Liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) can not be greater than or equal to 2.5 times the upper limits of normal (ULN)
  • Total bilirubin >= 1.5 x ULN within 14 days of enrollment, unless considered disease-related
  • Serum creatinine should be >= 1.5 x ULN within 14 days of enrollment
  • 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)
  • Known history of human immunodeficiency virus (HIV) or active hepatitis B or C
  • No major surgery within 4 weeks prior to trial enrollment
  • 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 post-menopausal or surgically sterilized women
  • Patient has received any standard or investigational therapy for their leukemia within 14 days before enrollment (except for hydroxyurea)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02071901

Locations
United States, Ohio
Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44106-5065
Contact: Sudipto Mukherjee, MD    216-445-9353    sekerem@ccf.org   
Principal Investigator: Sudipto Mukherjee         
Sponsors and Collaborators
Case Comprehensive Cancer Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Sudipto Mukherjee, MD Case Comprehensive Cancer Center
  More Information

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT02071901     History of Changes
Other Study ID Numbers: CASE4913  NCI-2014-00252  CASE4913  P30CA043703 
Study First Received: February 24, 2014
Last Updated: February 17, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Leukemia, Monocytic, Acute
Leukemia, Myelomonocytic, Acute
Hypereosinophilic Syndrome
Leukemia, Megakaryoblastic, Acute
Leukemia, Erythroblastic, Acute
Leukemia, Eosinophilic, Acute
Leukemia, Basophilic, Acute
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Eosinophilia
Leukocyte Disorders
Myeloproliferative Disorders

ClinicalTrials.gov processed this record on August 29, 2016