Acute Myelogenous LeukemiaPhase 2NCT00184054
Trial of Arsenic Trioxide With Ascorbic Acid in the Treatment of Adult Non-Acute Promyelocytic Leukemia (APL) Acute Myelogenous Leukemia
A Phase 2 study testing Arsenic Trioxide (ATO) and Ascorbic Acid in people with Acute Myelogenous Leukemia, run by University of Southern California at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myelogenous Leukemia
- What is being tested?
- Arsenic Trioxide (ATO) and Ascorbic Acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2002to Aug 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, 90032
About this study
Official title: Phase II Trial of Arsenic Trioxide With Ascorbic Acid in the Treatment of Adult Non-APL Acute Myelogenous Leukemia
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.
Read more
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
- Being tested
- Arsenic Trioxide (ATO), Ascorbic Acid
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arsenic Trioxide (ATO)Drug
Arsenic Trioxide .25 mg/kg/day
Ascorbic AcidDrug
Also called Vitamin C
Ascorbic Acid 1000 mg every other day for 25 days
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Arsenic Trioxide (ATO); Drug: Ascorbic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 1 year
Secondary outcomes (1)
Number of Participants With Severe (Grades 3-5) Adverse Events
Patients who received any amount of ATO plus Ascorbic Acid are included in the safety analyses.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2005 (estimated)
- Study startApr 2002
- Primary completionJun 2009
- Study completionAug 2011
Why it stopped: Competing studies
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Myelogenous LeukemiaStudies of the same condition, open and under way.
- More trials run by University of Southern CaliforniaThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dan Douer, MD, Principal investigator, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00184054
- Sponsor's protocol ID
- 9L-02-1
- Status last verified
- Jul 2014
- First submitted
- 12 Sep 2005
- Last updated
- 25 Jul 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Arsenic Trioxide With Ascorbic Acid in the Treatment of Adult Non-APL Acute Myelogenous Leukemia
- ClinicalTrials.gov ID
- NCT00184054
- Acronym / sponsor ID
- 9L-02-1
- Conditions
- Acute Myelogenous Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Competing studies
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Study start
- Apr 2002
- Primary completion
- Jun 2009 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 16 Sep 2005 (estimated)
- Results
- Posted 17 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arsenic Trioxide (ATO) Plus Ascorbic acid | Experimental | Drug: Arsenic Trioxide (ATO), Drug: Ascorbic AcidArsenic 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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:
- 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.
Key exclusion criteria (15 listed)
- Newly diagnosed patients older than age 55 who:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Arsenic Trioxide (ATO)Arsenic Trioxide .25 mg/kg/day | Drug | Arsenic Trioxide (ATO) Plus Ascorbic acid |
| Ascorbic AcidAlso: Vitamin CAscorbic Acid 1000 mg every other day for 25 days | Drug | Arsenic Trioxide (ATO) Plus Ascorbic acid |
Primary outcome
Number of Participants With a Response (Complete Remissions (CR) and Complete Remission With Incomplete Blood Count Recovery (CRi)
Time frame: Up to 1 year
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.
1 secondary outcome
Number of Participants With Severe (Grades 3-5) Adverse Events
Time frame: 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dan Douer, MD principal investigator
University of Southern California
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Arsenic Trioxide (ATO) and Ascorbic Acid in people with Acute Myelogenous Leukemia, run by University of Southern California at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With a Response (Complete Remissions (CR) and Complete Remission With Incomplete Blood Count Recovery (CRi) (time frame: Up to 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2014.