Acute Myelogenous Leukemia
Conditions
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.
Interventions
Arsenic Trioxide .25 mg/kg/day
DRUGAscorbic Acid
Ascorbic Acid 1000 mg every other day for 25 days
Sponsors
University of Southern California
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Response (Complete Remissions (CR) and Complete Remission With Incomplete Blood Count Recovery (CRi) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Patients who received any amount of ATO plus Ascorbic Acid are included in the safety analyses. |
Countries
United States
Participant flow
Recruitment details
Recruitment for this study opened in April 2002 and closed in May 2008. All subjects were seen at USC.
Pre-assignment details
The study has no pre-assignment. All subjects were given the same treatment.
Participants by arm
| Arm | Count |
|---|---|
| Arsenic Trioxide (ATO) Plus Ascorbic Acid All subjects received ATO 0.25 mg/kg/day intravenously for 25 days over a 35-day period and Ascorbic Acid 1000 mg/day intravenously every other day that ATO is given | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Arsenic Trioxide (ATO) Plus Ascorbic Acid |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 11 / 11 |
| serious Total, serious adverse events | 11 / 11 |
Outcome results
Primary
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.
Time frame: Up to 1 year
Population: All subjects who received at least 2 cycles of treatment as part of this study are included in the analysis of response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arsenic Trioxide (ATO) Plus Ascorbic Acid | Number of Participants With a Response (Complete Remissions (CR) and Complete Remission With Incomplete Blood Count Recovery (CRi) | CR | 1 participants |
| Arsenic Trioxide (ATO) Plus Ascorbic Acid | Number of Participants With a Response (Complete Remissions (CR) and Complete Remission With Incomplete Blood Count Recovery (CRi) | CRi | 5 participants |
| Arsenic Trioxide (ATO) Plus Ascorbic Acid | Number of Participants With a Response (Complete Remissions (CR) and Complete Remission With Incomplete Blood Count Recovery (CRi) | Treatment Failure | 4 participants |
| Arsenic Trioxide (ATO) Plus Ascorbic Acid | Number of Participants With a Response (Complete Remissions (CR) and Complete Remission With Incomplete Blood Count Recovery (CRi) | Not Evaluable | 1 participants |
Secondary
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.
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)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arsenic Trioxide (ATO) Plus Ascorbic Acid | Number of Participants With Severe (Grades 3-5) Adverse Events | Differentiation syndrome | 1 Participants |
| Arsenic Trioxide (ATO) Plus Ascorbic Acid | Number of Participants With Severe (Grades 3-5) Adverse Events | Anorexia | 1 Participants |
| Arsenic Trioxide (ATO) Plus Ascorbic Acid | Number of Participants With Severe (Grades 3-5) Adverse Events | Alanine aminotransferase increased | 1 Participants |
| Arsenic Trioxide (ATO) Plus Ascorbic Acid | Number of Participants With Severe (Grades 3-5) Adverse Events | Conjunctivitis infective | 2 Participants |
| Arsenic Trioxide (ATO) Plus Ascorbic Acid | Number of Participants With Severe (Grades 3-5) Adverse Events | Electrocardiogram QT corrected interval prolonged | 1 Participants |
| Arsenic Trioxide (ATO) Plus Ascorbic Acid | Number of Participants With Severe (Grades 3-5) Adverse Events | Neuropathy: sensory | 1 Participants |
| Arsenic Trioxide (ATO) Plus Ascorbic Acid | Number of Participants With Severe (Grades 3-5) Adverse Events | Sepsis | 4 Participants |