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

• Sponsor: Roswell Park Cancer Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02029417
• Collaborator: National Cancer Institute (NCI) (NIH), Teva Pharmaceutical Industries, Ltd. (Industry)
• Enrollment: 2
• Location: 1
• Arm: 1
• Duration (Months): 17
• Patients Per Site Per Month: 0.1

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: cytarabine; Drug: omacetaxine mepesuccinate; Drug: decitabine; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To study the complete response rate following OAG (omacetaxine mepesuccinate, cytarabine) in newly diagnosed acute myeloid leukemia patients unfit for intensive induction therapy.

2. 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:

1. 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

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: OAG and Decitabine for Newly Diagnosed Acute Myeloid Leukemia Patients Greater Than or Equal to 65 Years of Age
• Study Start Date: Jul 1, 2014
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Dec 1, 2015

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: ARA-C arabinofuranosylcytosine arabinosylcytosine Cytosar-U cytosine arabinoside ; Drug: omacetaxine mepesuccinate; Given SC; Other Names: CGX-635 homoharringtonine ; Drug: decitabine; Given IV; Other Names: 5-aza-dCyd 5AZA DAC ; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

• Responsible Party: Roswell Park Cancer Institute
• ClinicalTrials.gov Identifier: NCT02029417
• Other Study ID Numbers: I 245213; NCI-2013-02425; I 245213; P30CA016056
• First Posted: Jan 7, 2014
• Last Update Posted: May 9, 2016
• Last Verified: Apr 1, 2016

• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute; Myelodysplastic Syndromes; Cytarabine; Decitabine; Azacitidine; Homoharringtonine

Study Results

Participant Flow

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

1. Primary Outcome

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

2. Primary Outcome

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

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

Due to the study's early termination and low accrual no statistical inference of the primary aims were carried forth.

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.