Adult Acute Megakaryoblastic Leukemia (M7)Phase 1NCT01839240

Azacitidine, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With High-Risk Acute Myeloid Leukemia

A Phase 1 study testing azacitidine, cytarabine and mitoxantrone hydrochloride in people with Adult Acute Megakaryoblastic Leukemia (M7) and Adult Acute Monoblastic Leukemia (M5a), run by University of Chicago at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b)
What is being tested?: azacitidine, cytarabine and mitoxantrone hydrochloride
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 50 participants
Where: 1 siteUnited States
Study dates: 6 Jun 2012to 16 Aug 2019
Phase: Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients must have one of the following disease characteristics:
Therapy-related myeloid neoplasm (t-MN) age >= 18 years
Patients must have received cytotoxic chemotherapy, radiation, or a drug known to affect the properties of deoxyribonucleic acid (DNA) or cell growth, prior to current diagnosis of therapy-related myeloid neoplasm (t-MN); this broad definition is meant to include any prior therapy with chemicals that affect DNA replication, DNA integrity, or DNA structure, or chemicals that alter cell growth; this includes traditional cytotoxic chemotherapy, newer immunologic agents that have been shown to have cytotoxic activities in addition to immunosuppressive functions, and other chemicals; note that patients with primary AML could be diagnosed with a t- MN if morphology/cytogenetic analysis clearly indicated that the second process is not a relapse of the original disease
AML arising from an antecedent hematological disorder age >= 18 years
De novo AML in patients age >= 60 years
Relapsed and/or refractory AML >= 18 years

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Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment
Male and female patients must use an effective contraceptive method during the study and for at least 6 months after study treatment
Patients must be at least 2 weeks from major surgery, radiation therapy, participation in other investigational trials and must have recovered from clinically significant toxicities of these prior treatments
Ability to understand and willingness to sign the informed consent form

Who cannot join

Concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in this protocol
Diagnosis of acute promyelocytic leukemia (APL)
Use of investigational agents/any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea (note: for patients with hyperleukocytosis [white blood cell (WBC) > 20,000/uL], hydroxyurea [and leukapheresis, if clinically indicated] will be initiated and these patients will receive 5-azacytidine when the WBC count has decreased to =< 20,000/uL; hydroxyurea can be overlapped with 5-azacytidine in selected cases, after consultation with the study chair; hydroxyurea must be discontinued before the initiation of the HiDAC/mitoxantrone chemotherapy)
Prior treatment with 5-azacytidine followed immediately by HiDAC and mitoxantrone as proposed in this study (note: prior therapy with 5-azacytidine or decitabine or HiDAC or mitoxantrone would be allowed-in patients with relapsed/refractory disease- unless the prior therapy was identical to the schema/schedule proposed in this study)
Active second cancer other than specified; active cancer refers to cancer that requires systemic chemotherapy or biological therapy within 6 months of the study entry; patients who have received only hormonal therapy in the neoadjuvant or adjuvant setting in the past 6 months may participate in this study
Have any other severe concurrent disease, or have a history of serious organ dysfunction (e.g. uncontrolled or severe cardiovascular disease, diabetes, pulmonary disease, infection, psychiatric illness) that may in the judgment of the treating physician/ principal investigator place the patient at undue risk to undergo treatment
Pregnant or lactating patients
Any significant concurrent illness that would, in the judgment of the treating physician/principal investigator, compromise patient safety or compliance, or study participation

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637-1470

Other trials in United States

About this study

Official title: Phase I Investigation of the Feasibility of Combining 5-azacytidine With Highdose Cytarabine (HiDAC) and Mitoxantrone Chemotherapy in a Sequential Manner for Remission Induction in High-risk Acute Myelogenous Leukemia (AML)

This phase I trial studies the side effects and best dose of azacitidine when given together with cytarabine and mitoxantrone hydrochloride in treating patients with high-risk acute myeloid leukemia. Drugs used in chemotherapy, such as azacitidine, cytarabine, and mitoxantrone hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Azacitidine may also help cytarabine and mitoxantrone hydrochloride work better by making the cancer cells more sensitive to the drugs

Read the detailed description

PRIMARY OBJECTIVES:

To establish the recommended phase II dose of 5-azacytidine (azacitidine) when combined with high-dose cytarabine (HiDAC) and mitoxantrone (mitoxantrone hydrochloride) chemotherapy in high-risk acute myeloid leukemia (AML) patients.

SECONDARY OBJECTIVES:

To determine the complete remission (CR) rate following the use of induction chemotherapy regimen of 5-azacytidine followed by high-dose cytarabine (HiDAC) and mitoxantrone chemotherapy in high-risk AML patients.

II. To determine the toxicity of the combination regimen. III. To determine the disease-free survival (DFS) and overall survival (OS) of the patient population.

IV. To determine the gene expression levels of topoisomerase II and deoxycytidine kinase in leukemia blasts pre-treatment and following therapy with 5-azacytidine.

To collect specimens for banking for use in future research studies with a view to elucidating the predictors of response to epigenetic therapies.

OUTLINE: This is a dose-escalation study of azacitidine.

INDUCTION: Patients receive azacitidine intravenously (IV) over 10-40 minutes or subcutaneously (SC) once daily (QD) on days 1-5, cytarabine IV over 4 hours on days 6 and 10, and mitoxantrone hydrochloride IV over 60 minutes on days 6 and 10.

CONSOLIDATION: Patients receive azacitidine IV over 10-40 minutes or SC QD on days 1-5. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients ineligible for allogeneic stem cell transplantation continue on to maintenance.

MAINTENANCE: Patients receive azacitidine IV over 10-40 minutes or SC QD on days 1-5. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years.

Conditions: Adult Acute Megakaryoblastic Leukemia (M7), 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
Being tested: azacitidine, cytarabine, mitoxantrone hydrochloride, laboratory biomarker analysis
Medical subject headings: Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Erythroblastic, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

azacitidineDrug
Also called 5-AC, 5-azacytidine, azacytidine, Vidaza
Given IV or SC
cytarabineDrug
Also called ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U
Given IV
mitoxantrone hydrochlorideDrug
Also called CL 232315, DHAD, DHAQ, Novantrone
Given IV
laboratory biomarker analysisOther
Correlative studies

Study groups in NCT01839240
Study group	Role	What they receive
Treatment (azacitidine, cytarabine, and mitoxantrone)	Experimental	INDUCTION: Patients receive azacitidine IV over 10-40 minutes or SC QD on days 1-5, cytarabine IV over 4 hours on days 6 and 10, and mitoxantrone hydrochloride IV over 60 minutes on days 6 and 10. CONSOLIDATION: Patients receive azacitidine IV over 10-40 minutes or SC QD on days 1-5. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients ineligible for allogeneic stem cell transplantation continue on to maintenance. MAINTENANCE: Patients receive azacitidine IV over 10-40 minutes or SC QD on days 1-5. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Receives: Drug: azacitidine; Drug: cytarabine; Drug: mitoxantrone hydrochloride; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

Recommended phase II dose of azacitidine when combined with high-dose cytarabine and mitoxantrone hydrochloride, based on incidence of dose limiting toxicity (DLT) graded according to the National Cancer Institute Common Toxicity Criteria, version 4
DLT defined as any grade 4 or greater non-hematologic toxicity (except transient [less than 48 hours] nausea/vomiting, transient [less than 48 hours] liver function test derangements) or a grade 3 non-hematological toxicity lasting more than 7 days. Persistent bone marrow aplasia (in the absence of bone marrow involvement with disease) lasting more than 56 days would also be regarded as a DLT.
Measured: 56 days

Secondary outcomes (1)

Change in gene expression levels of topoisomerase II and deoxycytidine kinase in leukemic blasts pre-treatment and following therapy with azacitidine will be measured by real-time polymerase chain reaction (RT-PCR)
Will be compared using a two-sample t test. If the data do not appear to be normally distributed, a Wilcoxon rank sum test will be used in place of the t-test. Normality will be assessed using graphical techniques, such as normality probability plots.
Measured: From baseline to day 56

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 Jun 201216 Aug 2019

First posted24 Apr 2013 (estimated)
Study start6 Jun 2012
Primary completion16 Aug 2019
Study completion16 Aug 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Adult Acute Megakaryoblastic Leukemia (M7)Studies of the same condition, open and under way.
More trials run by University of ChicagoThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 50 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01839240
Sponsor's protocol ID: 12-0111
Other IDs: NCI-2012-02028
Status last verified: May 2020
First submitted: 19 Apr 2013
Last updated: 15 May 2020
Results posted: No
Data monitoring committee: No

Publications

Cahill KE, Karimi YH, Karrison TG, Jain N, Green M, Weiner H, Fulton N, Kadri S, Godley LA, Artz AS, Liu H, Thirman MJ, Le Beau MM, McNerney ME, Segal J, Larson RA, Stock W, Odenike O. A phase 1 study of azacitidine with high-dose cytarabine and mitoxantrone in high-risk acute myeloid leukemia. Blood Adv. 2020 Feb 25;4(4):599-606. doi: 10.1182/bloodadvances.2019000795.
PubMed 32074275