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

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Clinical Trial

Official title:

OAG and Decitabine for Newly Diagnosed Acute Myeloid Leukemia Patients Greater Than or Equal to 65 Years of Age

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02029417
• Other study ID #: I 245213
• Secondary ID: NCI-2013-02425I
• Status: Terminated
• Phase: Phase 2
• First received: January 6, 2014
• Last updated: January 11, 2016
• Start date: July 2014
• Est. completion date: December 2015

Study information

• Verified date: January 2016
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: December 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 65 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• 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)
• Leukemia
• Leukemia, Erythroblastic, Acute
• Leukemia, Megakaryoblastic, Acute
• Leukemia, Monocytic, Acute
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic
• Myelodysplastic Syndromes
• Preleukemia
• Secondary Acute Myeloid Leukemia
• Untreated Adult Acute Myeloid Leukemia

Intervention

Drug:
• cytarabine
Given SC
• omacetaxine mepesuccinate
Given SC
• decitabine
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York

Sponsors (3)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute	National Cancer Institute (NCI), Teva Pharmaceutical Industries, Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 4 years	No
Primary	Frequency of adverse events, graded according to NCI CTCAE v4.0	Tabulated by grade across.	Up to 30 days after last dose of study drugs	Yes