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

NCT00184054 | Terminated Phase 2 Results

• 1 other identifier: 9L-02-1
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a Response (Complete Remissions (CR) and Complete Remission With Incomplete Blood Count Recovery (CRi)

  Complete Remission (CR): ANC \>=1000/mcl, Platelet count \>=100,000/mcl, Bone marrow \<5% blasts. Complete Remission with incomplete blood count recovery (CRi): Same as CR but ANC may be \<1,000/mcl and/or platelet count \<100,000/mcl. Patients who failed to achieve CR or CRi after two cycles were considered treatment failures. Patients who did not complete at least two cycles were not evaluated for response.

  Up to 1 year

Secondary Outcomes (1)

• Number of Participants With Severe (Grades 3-5) Adverse Events

  Days 1, 8, 15, 21, 28, 35 of each cycle and at end of treatment (30 days after last dose or start of new therapy)

Study Arms (1)

Arsenic Trioxide (ATO) Plus Ascorbic acid

EXPERIMENTAL

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

Drug: Arsenic Trioxide (ATO); Drug: Ascorbic Acid

Interventions

Arsenic Trioxide (ATO) DRUG

Arsenic Trioxide .25 mg/kg/day

Arsenic Trioxide (ATO) Plus Ascorbic acid

Ascorbic Acid DRUG

Ascorbic Acid 1000 mg every other day for 25 days

Also known as: Vitamin C

Arsenic Trioxide (ATO) Plus Ascorbic acid

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Southern California: lead

Study Sites (1)

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, 90032, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Arsenic Trioxide; Ascorbic Acid

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Results Point of Contact

• Title: Victoria Soto, Project Specialist, Clinical Investigations Support Office
• Organization: USC Norris Comprehensive Cancer Center

victoria.soto@med.usc.edu

323-226-6384

Study Officials

• Dan Douer, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 16, 2005
• Study Start: April 1, 2002
• Primary Completion: June 1, 2009
• Study Completion: August 1, 2011
• Last Updated: July 25, 2014
• Results First Posted: July 17, 2014

Record last verified: 2014-07

Locations

US (1)