Arsenic Trioxide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

A Phase II Study of Arsenic Trioxide in Patients With Relapsed and/or Refractory Acute Myeloid Leukemia (AML) and Mutated Nucleophosmin 1 (NPM1) Gene

This phase II trial studies how well arsenic trioxide works in treating patients with relapsed or refractory acute myeloid leukemia. Drugs used in chemotherapy, such as arsenic trioxide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

Study Overview

• Status: Withdrawn
• Conditions: Recurrent Adult Acute Myeloid Leukemia; 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)
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: arsenic trioxide

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the complete remission rate of relapsed and refractory acute myeloid leukemia (AML) patients with Mutated Nucleophosmin 1 (NPM1) gene.

SECONDARY OBJECTIVES:

I. Determine the duration of remission in these patients. II. Determine the in vivo biological effect of arsenic trioxide in AML with mutated NPM1.

OUTLINE:

Patients receive arsenic trioxide intravenously (IV) over 1-2 hours daily for up to 45 days. Patients achieving complete remission, receive arsenic trioxide IV over 1-2 hours daily 5 days a week for 4 weeks. Treatment repeats every 8 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• AML, any French- American- British (FAB) subtype except M3, with confirmed mutation in the NPM1 gene
• Relapsed and/or refractory AML from any duration of complete remission (CR); any number of prior therapies allowed
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2, life expectancy > 3 months
• Serum creatinine =< 2.0 mg/dL
• Bilirubin =< 2.0 mg/dL
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN)
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies; pregnancy tests must be obtained in women; sexually active males or females may not participate unless they have agreed to use an effective contraceptive method
• Patients who are currently receiving another investigational drug
• Patients who are currently receiving other anti-cancer agents
• Uncontrolled systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
• Known hypersensitivity to arsenic trioxide

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (arsenic trioxide); Patients receive arsenic trioxide IV over 1-2 hours daily for up to 45 days. Patients achieving complete remission, receive arsenic trioxide IV over 1-2 hours daily 5 days a week for 4 weeks. Treatment repeats every 8 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.	Other: laboratory biomarker analysis; Correlative studies; Drug: arsenic trioxide; Given IV; Other Names: Arsenic (III) Oxide; Arsenic Sesquioxide; Arsenous Acid Anhydride; AS2O3; Trisenox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of complete remission following arsenic trioxide induction	After 4 weeks of therapy

Secondary Outcome Measures

Outcome Measure	Time Frame
Median duration of remission	Time from documented complete remission until time of disease relapse, assessed up to 2 years

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Anticipated): May 1, 2015

Study Registration Dates

• First Submitted: April 15, 2013
• First Submitted That Met QC Criteria: April 15, 2013
• First Posted (Estimate): April 18, 2013

Study Record Updates

• Last Update Posted (Actual): May 21, 2018
• Last Update Submitted That Met QC Criteria: May 16, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Monocytic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute; Antineoplastic Agents; Arsenic Trioxide
• Other Study ID Numbers: IRB-26938; NCI-2013-00767 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); HEMAML0023 (Other Identifier: OnCore)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No