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Omacetaxine Mepesuccinate, Cytarabine, and Decitabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

Primary Purpose

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0)

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
cytarabine
omacetaxine mepesuccinate
decitabine
laboratory biomarker analysis
Sponsored by
Roswell Park Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients who are not eligible for standard induction chemotherapy (or any standard therapy known to be life prolonging) because of poor performance status, significant tissue comorbidities, or unfavorable risk of disease
  • Have an unequivocal histologic diagnosis of acute myeloid leukemia (AML) (including secondary AML)
  • No prior therapy for AML except hydroxyurea to control counts
  • Must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
  • Subject or legal representative must understand the investigational nature of this study and sign an independent ethics committee/institutional review board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

  • Subjects with the diagnosis of acute promyelocytic leukemia (t[15;17])
  • Unwilling or unable to follow protocol requirements
  • Any condition which in the investigator's opinion deems the subject an unsuitable candidate to receive study drug
  • Patients with sickle cell disease and sickle cell crisis
  • Received an investigational agent for another disease within 30 days prior to enrollment
  • The patient has an uncontrolled and active infection that would preclude study conduct and assessment

Sites / Locations

  • Roswell Park Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (cytarabine, omacetaxine mepesuccinate, decitabine)

Arm Description

INDUCTION CHEMOTHERAPY: Patients receive cytarabine SC BID and omacetaxine mepesuccinate SC BID on days 1-14. Treatment for induction therapy repeats every 28 days for up to 4 courses or until patients achieve CR in the absence of disease progression or unacceptable toxicity. CONSOLIDATION THERAPY: Patients alternate courses between decitabine and OAG. Patients receive decitabine IV on days 1-5. Patients alternate with OAG courses, comprising cytarabine SC BID on days 1-7 and omacetaxine mepesuccinate SC BID on days 1-7. Treatment repeats every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Proportion of the Evaluable Population of Interest Who Experience a Complete Response in the Poor and Good Prognosis Groups
Defined as recovery of morphologically normal bone marrow (< 5% blasts) and blood counts (absolute neutrophil count >= 1x10^9/L, platelet counts >= 100x10^9/LO) and rare circulating leukemic blasts or evidence of extramedullary disease. Analyzed using exact binomial probabilities in a two-stage design. The number of responses will be tabulated.
Frequency of Adverse Events, Graded According to NCI CTCAE v4.0
Maximum grade per participant of any AE.

Secondary Outcome Measures

Full Information

First Posted
January 6, 2014
Last Updated
April 5, 2016
Sponsor
Roswell Park Cancer Institute
Collaborators
National Cancer Institute (NCI), Teva Pharmaceutical Industries, Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT02029417
Brief Title
Omacetaxine Mepesuccinate, Cytarabine, and Decitabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia
Official Title
OAG and Decitabine for Newly Diagnosed Acute Myeloid Leukemia Patients Greater Than or Equal to 65 Years of Age
Study Type
Interventional

2. Study Status

Record Verification Date
April 2016
Overall Recruitment Status
Terminated
Why Stopped
Major revisions needed in study
Study Start Date
July 2014 (undefined)
Primary Completion Date
November 2015 (Actual)
Study Completion Date
December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Roswell Park Cancer Institute
Collaborators
National Cancer Institute (NCI), Teva Pharmaceutical Industries, Ltd.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial studies the side effects and how well omacetaxine mepesuccinate, cytarabine, and decitabine work in treating older patients with newly diagnosed acute myeloid leukemia. Omacetaxine mepesuccinate, cytarabine, and decitabine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Detailed Description
PRIMARY OBJECTIVES: I. To study the complete response rate following OAG (omacetaxine mepesuccinate, cytarabine) in newly diagnosed acute myeloid leukemia patients unfit for intensive induction therapy. II. To assess the toxicity of OAG using the Cancer Therapy Evaluation Program (CTEP) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.0). SECONDARY OBJECTIVES: I. To study the disease-free and overall survival of OAG and decitabine in newly diagnosed acute myeloid leukemia patients unfit for intensive induction therapy. OUTLINE: INDUCTION CHEMOTHERAPY: Patients receive cytarabine subcutaneously (SC) twice daily (BID) and omacetaxine mepesuccinate SC BID on days 1-14. Treatment for induction therapy repeats every 28 days for up to 4 courses or until patients achieve complete response (CR) in the absence of disease progression or unacceptable toxicity. CONSOLIDATION THERAPY: Patients alternate courses between decitabine and OAG. Patients receive decitabine intravenously (IV) on days 1-5. Patients alternate with OAG courses, comprising cytarabine SC BID on days 1-7 and omacetaxine mepesuccinate SC BID on days 1-7. Treatment repeats every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, 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 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, Untreated Adult Acute Myeloid Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (cytarabine, omacetaxine mepesuccinate, decitabine)
Arm Type
Experimental
Arm Description
INDUCTION CHEMOTHERAPY: Patients receive cytarabine SC BID and omacetaxine mepesuccinate SC BID on days 1-14. Treatment for induction therapy repeats every 28 days for up to 4 courses or until patients achieve CR in the absence of disease progression or unacceptable toxicity. CONSOLIDATION THERAPY: Patients alternate courses between decitabine and OAG. Patients receive decitabine IV on days 1-5. Patients alternate with OAG courses, comprising cytarabine SC BID on days 1-7 and omacetaxine mepesuccinate SC BID on days 1-7. Treatment repeats every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
cytarabine
Other Intervention Name(s)
ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside
Intervention Description
Given SC
Intervention Type
Drug
Intervention Name(s)
omacetaxine mepesuccinate
Other Intervention Name(s)
CGX-635, homoharringtonine
Intervention Description
Given SC
Intervention Type
Drug
Intervention Name(s)
decitabine
Other Intervention Name(s)
5-aza-dCyd, 5AZA, DAC
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Proportion of the Evaluable Population of Interest Who Experience a Complete Response in the Poor and Good Prognosis Groups
Description
Defined as recovery of morphologically normal bone marrow (< 5% blasts) and blood counts (absolute neutrophil count >= 1x10^9/L, platelet counts >= 100x10^9/LO) and rare circulating leukemic blasts or evidence of extramedullary disease. Analyzed using exact binomial probabilities in a two-stage design. The number of responses will be tabulated.
Time Frame
Up to 4 years
Title
Frequency of Adverse Events, Graded According to NCI CTCAE v4.0
Description
Maximum grade per participant of any AE.
Time Frame
Up to 30 days after last dose of study drugs

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients who are not eligible for standard induction chemotherapy (or any standard therapy known to be life prolonging) because of poor performance status, significant tissue comorbidities, or unfavorable risk of disease Have an unequivocal histologic diagnosis of acute myeloid leukemia (AML) (including secondary AML) No prior therapy for AML except hydroxyurea to control counts Must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation Subject or legal representative must understand the investigational nature of this study and sign an independent ethics committee/institutional review board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: Subjects with the diagnosis of acute promyelocytic leukemia (t[15;17]) Unwilling or unable to follow protocol requirements Any condition which in the investigator's opinion deems the subject an unsuitable candidate to receive study drug Patients with sickle cell disease and sickle cell crisis Received an investigational agent for another disease within 30 days prior to enrollment The patient has an uncontrolled and active infection that would preclude study conduct and assessment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Evelena Ontiveros
Organizational Affiliation
Roswell Park Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Omacetaxine Mepesuccinate, Cytarabine, and Decitabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

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