Acute Myeloid Leukemia
Conditions
Keywords
Leukemia, AML, chemotherapy-naïve, Clofarabine, Clofarex, Clolar, Idarubicin, Idamycin, Cytarabine, Ara-C, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride
Brief summary
The goal of this clinical research study is to learn if the combination of clofarabine, cytarabine, and idarubicin can help to control Acute Myeloid Leukemia (AML) in patients who are between the ages of 18 and 60 years old. The safety of this study drug combination will also be studied.
Detailed description
The Study Drugs: Clofarabine is designed to interfere with the growth and development of cancer cells. Idarubicin is designed to cause breaks in DNA (the genetic material of cells) of cancer cells and interfere with their growth and development. Cytarabine is designed to insert itself into DNA of cancer cells and stop the DNA from repairing itself. Study Drug Administration: If you are found to be eligible to take part in this study, you will receive the study drug combination over 1 or 2 Induction Cycles of treatment. Whether or not you receive a second Induction Cycle depends on the disease's response to the first Induction Cycle. Each Induction Cycle will last about 4-6 weeks, depending on your reaction to the study drugs. During each Induction Cycle, you will receive the study drugs by the following schedule: * Clofarabine, by vein, over 1-2 hours on Days 1-5. * Cytarabine, by vein, over 2-3 hours on Days 1-5. * Idarubicin, by vein, over about 30-60 minutes on Days 1-3. If the disease shows a response to the treatment during the Induction Cycle(s), you may continue to receive up to 6 Consolidation Cycles of treatment. Each Consolidation Cycle will last about 3-10 weeks, depending on your reaction to the study drugs. During each Consolidation Cycle, you will receive the study drugs by the following schedule: * Clofarabine, by vein, over 1-2 hours on Days 1-3. * Cytarabine, by vein, over 2-3 hours on Days 1-3. * Idarubicin, by vein, over 30-60 minutes on Days 1-2. Study Visits: On Day 1 of every cycle: * You will have a physical exam, including measurement of your weight and vital signs. * Your performance status will be recorded. * Blood (about 1-2 teaspoons) will be drawn for routine tests. Throughout the study, you will have blood and bone marrow tests to check the status of the disease and to help the doctor decide if you need additional cycles of treatment. Blood (about 1-2 tablespoons each time) will be drawn 2 times each week for routine tests during the Induction Cycles. This blood will also be drawn every week during the Consolidation Cycles. About 3 weeks after you first receive the study drugs, you will have a bone marrow aspirate to check the status of the disease. After that, you will have a bone marrow aspirate every 2 weeks (or more often if your doctor thinks it is needed). However, if the routine blood tests show that there is still leukemia present, these bone marrow samples may not need to be collected. You will need to stay in Houston for up to the first 5 weeks of treatment. After that, you will need to return to Houston to receive treatment, but you can have check-up visits and blood tests with your local doctor in between treatments. Length of Study: You will be able to receive the study drugs for up to 8 cycles (a maximum of 2 induction cycles and 6 consolidation cycles). You will be taken off study if the disease gets worse or you experience any intolerable side effects. Follow-up Scan: Within 8 weeks after you have stopped taking the study drug, you will have an echocardiogram or a Multiple gate acquisition scan (MUGA) scan to check your heart function. This is an investigational study. Cytarabine and idarubicin are both FDA approved and commercially available for the treatment of patients with AML. Clofarabine is FDA approved and commercially available for the treatment of patients with acute lymphoblastic leukemia (ALL). The use of this drug combination for the treatment of AML is investigational. Up to 60 patients will take part in this study. All will be enrolled at M. D. Anderson.
Interventions
DRUGIdarubicin
Induction Cycle: 10 mg/m\^2 IV over approximately 30 minutes daily for 3 days (days 1-3), following clofarabine by 1 to 2 hours
DRUGCytarabine
Induction Cycle: 1 g/m\^2 IV over approximately 2 hours daily for 5 days (days 1-5), follow clofarabine by 3 to 6 hours.
DRUGClofarabine
Induction Cycle: 20 mg/m\^2 IV over approximately 1 hour daily for 5 days (days 1-5)
Sponsors
Genzyme, a Sanofi Company
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of AML (World Health Organization (WHO) classification) 2. Patients must be chemotherapy-naïve, i.e. not have received any prior cytotoxic chemotherapy for AML (with the exception of hydroxyurea). They could have received prior therapy with hypomethylating agents, targeted, or biological agents. 3. Age 18 to 60 years. 4. Eastern Cooperative Oncology Group (ECOG) performance status \</= 2. 5. Serum creatinine \</= 1.0 mg/dL; if serum creatinine \> 1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be \> 60 mL/min/1.73m\^2 as calculated by the Modification of Diet in Renal Disease equation where Predicted GFR (ml/min/1.73m\^2)=186 \* (serum creatinine)\^-1.154 x (age in years)\^-0.023 \* (0.742 if patient is female) \* (1.212 if patient is black), where SCr is serum creatinine measured in mg/dL. serum bilirubin \</= 1.5 \* upper limit of normal (ULN) (unless increase is due to hemolysis or a congenital disorder); serum transaminases (SGPT and/or SGOT) \</= 2.5 \* ULN. 6. Cardiac ejection fraction \>/= 45% (by either echocardiography or MUGA scan). 7. Ability to understand and provide signed informed consent.
Exclusion criteria
1. Patients with acute promyelocytic leukemia (APL). 2. Any coexisting medical condition that in the judgment of the treating physician is likely to interfere with study procedures or results. 3. Nursing women, women of childbearing potential with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception (such as birth control pills, intrauterine device (IUD), diaphragm, abstinence, or condoms by their partner) over the entire course of therapy. 4. Active and uncontrolled infection requiring therapy with IV antibiotics or antifungal therapy. Prior or concurrent history of one or more opportunistic infections (e.g., cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response: Number of Participants With Complete Remission or Complete Remission Without Platelet Recovery | 8 weeks after Induction therapy (induction cycle 4-6 weeks) | Overall Response (CR+CRp) defined as Complete remission (CR): Disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count \> 1.0 x 10\^9/L and platelet count \> 100 x 10\^9/L, and normal bone marrow differential (\< 5% blasts); and, Complete Remission without Platelet Recovery (CRp): Peripheral blood and bone marrow results as for CR, but with platelet counts of \< 100 x 10\^9/L. Response evaluated within 8 weeks after induction therapy. |
| Median Event-Free Survival (EFS) | 2 years | Event-free survival (EFS) defined as time from start of treatment to first documentation of disease relapse or death. Bayesian time-to-event model will be used to monitor progression free survival. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period 1/28/2010 - 2/20/2013; All participants were registered at The University of Texas MD Anderson Cancer Center.
Pre-assignment details
Of the 63 participants registered, four (4) were excluded prior to study starting.
Participants by arm
| Arm | Count |
|---|---|
| Clofarabine, Cytarabine + Idarubicin Induction Cycle: Clofarabine 20 mg/m\^2 intravenous (IV) daily for 5 days; Idarubicin 10 mg/m\^2 IV daily for 3 days; Cytarabine 1 g/m\^2 IV daily for 5 days | 59 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Clofarabine, Cytarabine + Idarubicin |
|---|---|
| Age, Continuous | 48 years |
| Region of Enrollment United States | 59 participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 56 / 59 |
| serious Total, serious adverse events | 36 / 59 |
Outcome results
Primary
Median Event-Free Survival (EFS)
Event-free survival (EFS) defined as time from start of treatment to first documentation of disease relapse or death. Bayesian time-to-event model will be used to monitor progression free survival.
Time frame: 2 years
Population: Two of the fifty-nine participants were not included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clofarabine, Cytarabine + Idarubicin | Median Event-Free Survival (EFS) | 13.5 Months |
Primary
Overall Response: Number of Participants With Complete Remission or Complete Remission Without Platelet Recovery
Overall Response (CR+CRp) defined as Complete remission (CR): Disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count \> 1.0 x 10\^9/L and platelet count \> 100 x 10\^9/L, and normal bone marrow differential (\< 5% blasts); and, Complete Remission without Platelet Recovery (CRp): Peripheral blood and bone marrow results as for CR, but with platelet counts of \< 100 x 10\^9/L. Response evaluated within 8 weeks after induction therapy.
Time frame: 8 weeks after Induction therapy (induction cycle 4-6 weeks)
Population: Two of the fifty-nine participants were not evaluable.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clofarabine, Cytarabine + Idarubicin | Overall Response: Number of Participants With Complete Remission or Complete Remission Without Platelet Recovery | Complete Remission | 42 participants |
| Clofarabine, Cytarabine + Idarubicin | Overall Response: Number of Participants With Complete Remission or Complete Remission Without Platelet Recovery | Complete Remission without Platelet Recovery | 3 participants |