Omacetaxine Mepesuccinate, Cytarabine, and Decitabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia
Study Details
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:
-
To study the complete response rate following OAG (omacetaxine mepesuccinate, cytarabine) in newly diagnosed acute myeloid leukemia patients unfit for intensive induction therapy.
-
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:
- 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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Treatment (cytarabine, omacetaxine mepesuccinate, decitabine) 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. |
Drug: cytarabine
Given SC
Other Names:
Drug: omacetaxine mepesuccinate
Given SC
Other Names:
Drug: decitabine
Given IV
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
Outcome Measures
Primary Outcome Measures
- Proportion of the Evaluable Population of Interest Who Experience a Complete Response in the Poor and Good Prognosis Groups [Up to 4 years]
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 [Up to 30 days after last dose of study drugs]
Maximum grade per participant of any AE.
Eligibility Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263 |
Sponsors and Collaborators
- Roswell Park Cancer Institute
- National Cancer Institute (NCI)
- Teva Pharmaceutical Industries, Ltd.
Investigators
- Principal Investigator: Evelena Ontiveros, Roswell Park Cancer Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- I 245213
- NCI-2013-02425
- I 245213
- P30CA016056
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Treatment (Cytarabine, Omacetaxine Mepesuccinate, Decitabine) |
---|---|
Arm/Group 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. cytarabine: Given SC omacetaxine mepesuccinate: Given SC decitabine: Given IV laboratory biomarker analysis: Correlative studies |
Period Title: Overall Study | |
STARTED | 2 |
COMPLETED | 0 |
NOT COMPLETED | 2 |
Baseline Characteristics
Arm/Group Title | Treatment (Cytarabine, Omacetaxine Mepesuccinate, Decitabine) |
---|---|
Arm/Group 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. cytarabine: Given SC omacetaxine mepesuccinate: Given SC decitabine: Given IV laboratory biomarker analysis: Correlative studies |
Overall Participants | 2 |
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
75
(1.8)
|
Sex: Female, Male (Count of Participants) | |
Female |
0
0%
|
Male |
2
100%
|
Outcome Measures
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 |
Outcome Measure Data
Analysis Population Description |
---|
Due to the study's early termination and low accrual, data were not collected for this assessment. |
Arm/Group Title | Treatment (Cytarabine, Omacetaxine Mepesuccinate, Decitabine) |
---|---|
Arm/Group 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. cytarabine: Given SC omacetaxine mepesuccinate: Given SC decitabine: Given IV laboratory biomarker analysis: Correlative studies |
Measure Participants | 0 |
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 |
Outcome Measure Data
Analysis Population Description |
---|
All treated and eligible patients. |
Arm/Group Title | Treatment (Cytarabine, Omacetaxine Mepesuccinate, Decitabine) |
---|---|
Arm/Group 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. cytarabine: Given SC omacetaxine mepesuccinate: Given SC decitabine: Given IV laboratory biomarker analysis: Correlative studies |
Measure Participants | 2 |
Grade 1 |
0
0%
|
Grade 2 |
0
0%
|
Grade 3 |
0
0%
|
Grade 4 |
2
100%
|
Adverse Events
Time Frame | ||
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | Treatment (Cytarabine, Omacetaxine Mepesuccinate, Decitabine) | |
Arm/Group 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. cytarabine: Given SC omacetaxine mepesuccinate: Given SC decitabine: Given IV laboratory biomarker analysis: Correlative studies | |
All Cause Mortality |
||
Treatment (Cytarabine, Omacetaxine Mepesuccinate, Decitabine) | ||
Affected / at Risk (%) | # Events | |
Total | / (NaN) | |
Serious Adverse Events |
||
Treatment (Cytarabine, Omacetaxine Mepesuccinate, Decitabine) | ||
Affected / at Risk (%) | # Events | |
Total | 2/2 (100%) | |
Infections and infestations | ||
Sepsis | 2/2 (100%) | 2 |
Other (Not Including Serious) Adverse Events |
||
Treatment (Cytarabine, Omacetaxine Mepesuccinate, Decitabine) | ||
Affected / at Risk (%) | # Events | |
Total | 2/2 (100%) | |
Blood and lymphatic system disorders | ||
Febrile neutropenia | 1/2 (50%) | 4 |
Cardiac disorders | ||
Acute myocardial infarction | 1/2 (50%) | 1 |
Atrial flutter | 1/2 (50%) | 1 |
Myocardial infarction | 1/2 (50%) | 1 |
Tachycardia | 1/2 (50%) | 1 |
Gastrointestinal disorders | ||
Abdominal pain | 1/2 (50%) | 1 |
Constipation | 1/2 (50%) | 1 |
Diarrhoea | 1/2 (50%) | 1 |
Nausea | 1/2 (50%) | 1 |
Retroperitoneal haematoma | 1/2 (50%) | 1 |
General disorders | ||
Chest pain | 1/2 (50%) | 1 |
Malaise | 1/2 (50%) | 1 |
Multi-organ failure | 1/2 (50%) | 1 |
Oedema | 1/2 (50%) | 1 |
Pain | 1/2 (50%) | 1 |
Hepatobiliary disorders | ||
Jaundice | 1/2 (50%) | 1 |
Infections and infestations | ||
Candidiasis | 1/2 (50%) | 1 |
Cellulitis | 1/2 (50%) | 1 |
Injury, poisoning and procedural complications | ||
Fall | 1/2 (50%) | 1 |
Investigations | ||
Blood bilirubin increased | 1/2 (50%) | 1 |
Blood creatinine increased | 1/2 (50%) | 1 |
Platelet count decreased | 1/2 (50%) | 2 |
Metabolism and nutrition disorders | ||
Decreased appetite | 1/2 (50%) | 1 |
Fluid overload | 1/2 (50%) | 1 |
Hypoalbuminaemia | 1/2 (50%) | 1 |
Tumour lysis syndrome | 1/2 (50%) | 1 |
Musculoskeletal and connective tissue disorders | ||
Back pain | 1/2 (50%) | 1 |
Muscular weakness | 1/2 (50%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||
Cough | 1/2 (50%) | 1 |
Dyspnoea | 1/2 (50%) | 3 |
Pleural effusion | 1/2 (50%) | 1 |
Respiratory distress | 1/2 (50%) | 1 |
Respiratory failure | 2/2 (100%) | 2 |
Tachypnoea | 2/2 (100%) | 2 |
Wheezing | 1/2 (50%) | 1 |
Vascular disorders | ||
Deep vein thrombosis | 1/2 (50%) | 1 |
Hypotension | 1/2 (50%) | 1 |
Thrombophlebitis | 1/2 (50%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Senior Administrator, Compliance - Clinical Research Services |
---|---|
Organization | Roswell Park Cancer Institute |
Phone | 716-845-2300 |
- I 245213
- NCI-2013-02425
- I 245213
- P30CA016056