Trial of Arsenic Trioxide With Ascorbic Acid in the Treatment of Adult Non-Acute Promyelocytic Leukemia (APL) Acute Myelogenous Leukemia

NCT ID: NCT00184054

Last Updated: 2014-07-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-04-30
• Study Completion Date: 2011-08-31

Brief Summary

This clinical research study is for patients with acute myelogenous leukemia (in short AML) that did not respond to previous treatment or unable to receive chemotherapy.

Arsenic has been used as a drug for many centuries. While arsenic containing drugs were used in the past for cancer treatments, the major use of arsenic in western countries has been for the treatment of uncommon tropical illnesses, such as sleeping sickness. Recently, some new information suggests that arsenic in a form called arsenic trioxide may also be useful to treat some cancers of the blood, such as leukemia, lymphoma and myeloma. Studies from China and the USA showed that patients with a type of blood cancer called acute promyelocytic leukemia, whose disease failed to respond to other treatments, responded very well to arsenic trioxide. Studies done in laboratories in the United States have shown that arsenic can kill AML cells growing in culture dishes.

Ascorbic acid (vitamin C), a natural supplement in our diet, has long been involved with cancer prevention. Laboratory tests have shown that although arsenic trioxide by itself can kill AML cells in the test tube, when vitamin C is added to arsenic trioxide in a test tube, the death of the leukemia cells increases significantly.

The purpose of this study is to find out if the combination of arsenic trioxide (Trisenox) and ascorbic acid is effective in the treatment of patients who have AML. The second purpose is to study how the two drugs affect cells in the laboratory. Samples from the blood and bone marrow (the part of the body that makes blood cells) will be collected, at specific times during treatment, in order to study them in the laboratory. By studying blood and marrow cells, researchers hope to learn the mechanisms by which the drugs work.

Conditions

Acute Myelogenous Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arsenic Trioxide (ATO) Plus Ascorbic acid

Arsenic Trioxide (ATO) given at 0.25 mg/kg/day intravenously for 25 days over a 35-day period.

Ascorbic Acid given at 1000 mg/day intravenously every other day that ATO is given

Group Type: EXPERIMENTAL

Arsenic Trioxide (ATO)

Intervention Type: DRUG

Arsenic Trioxide .25 mg/kg/day

Ascorbic Acid

Intervention Type: DRUG

Ascorbic Acid 1000 mg every other day for 25 days

Interventions

Arsenic Trioxide (ATO)

Arsenic Trioxide .25 mg/kg/day

Intervention Type: DRUG

Ascorbic Acid

Ascorbic Acid 1000 mg every other day for 25 days

Intervention Type: DRUG

Other Intervention Names

Vitamin C

Eligibility Criteria

Inclusion Criteria

• Diagnosis of non-APL AML (FAB subtypes M0 - M7 but excluding M3) confirmed by myeloperoxidase stain and/or flow cytometry.
• For patients of age 18 or older - only refractory or relapsed AML will be included. Refractory disease is defined as newly diagnosed patients who fulfill ONE of the following criteria:

• Patient aged 60 years or younger, who have failed to achieve a complete remission after at least two cycles of front line induction chemotherapy.
• Patients of any age who have AML, that is post myelodysplastic syndrome (MDS), who failed to achieve a complete remission after at least one cycle of front line induction chemotherapy.
• Patients aged 60 years or older who failed to achieve a complete remission after at least one cycle of front line induction chemotherapy.
• Newly diagnosed patients aged 55 or older who will not receive intensive anti-leukemia chemotherapy can also be enrolled.
• Post-myelodysplasia AML and secondary AML are included.
• Stem cell transplantation failures are included.
• Karnofsky performance status greater or equal to 50%.
• Adequate renal function (creatinine < 1.5 x ULN or creatinine clearance > 60 ml/min) and hepatic function (transaminases < 2.5 x ULN, serum total bilirubin < 3 mg/dl).
• Females of childbearing potential must have a negative serum pregnancy test prior to enrollment on the study, and both women and men must use an effective birth control method while on the study.
• Signed consent.

Exclusion Criteria

• Newly diagnosed patients older than age 55 who:

• Refuse chemotherapy when their treating physician recommends standard anti-leukemia induction chemotherapy.
• Have a Karnofsky performance status of greater or equal to 70%, aged < 75 years and has no prior myelodysplastic syndrome.
• Have a risk/benefit ratio that gives their treating physician good reason for administration of standard anti-leukemia induction chemotherapy.
• Patients who have already been treated with arsenics.
• CML in blastic crisis.
• Patients with cardiopathies including recurrent supraventricular arrhythmia and any type of sustained ventricular arrhythmia or conduction block (A-V block grade II or III, LBBB).
• Patients with HIV.
• Pregnant or breastfeeding women.
• QT interval > 460 msec in the presence of serum potassium > 4.0 mEq/L and magnesium > 1.8 mg/dL.
• Pre-existing neurotoxicity/neuropathy of Grade 2 or greater according to the NCI Common Toxicity Criteria Version 2.
• History of preexisting neurological disorders (grade 3 or higher by the NCI Common Toxicity Criteria; in particular, seizure disorders).
• Patients with an underlying medical condition that could be aggravated by the treatment or life threatening disease unrelated to AML as evaluated by the enrolling physician.
• Patients with active second malignancy, excluding adequately treated basal or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
• Inability or unwillingness to comply with the treatment protocol.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Southern California

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dan Douer, MD

Role: PRINCIPAL_INVESTIGATOR

University of Southern California

Locations

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States

Countries

United States

Other Identifiers

9L-02-1

Identifier Type: -

Identifier Source: org_study_id