Leukemia, Myeloid, Acute
Conditions
Keywords
Vosaroxin, Cytarabine, Remission Induction, Safety, Progression-Free Survival, Mortality Rate, Length of Stay
Brief summary
This is a pilot efficacy assessment clinical trial of vosaroxin and cytarabine for the treatment of adults 60 years of age or older with previously untreated acute myeloid leukemia. A total of 17 evaluable patients are planned to be treated on the study.
Detailed description
Primary objective: rate of complete remission (morphologic complete remission or morphologic complete remission with incomplete blood count recovery) Secondary objectives: (1) safety of this combination in induction therapy of older patients previously unexposed to intensive chemotherapy; (2) progression-free survival; (3) length of stay in hospital for induction; (4) 30- and 60-day mortality rate. The treatment period will include up to 4 cycles of treatment (induction 1, induction 2, consolidation 1, and consolidation 2). In each cycle, the first day of study treatment will be considered day 1. * Each cycle will include vosaroxin treatment on days 1 and 4 (total of 2 days) and cytarabine treatment on days 1-5 (total of 5 days) followed by a variable interval required to achieve hematologic recovery, defined as absolute neutrophil count (ANC) \> 1000 cells/L. * Up to 2 cycles of consolidation treatment may be completed by eligible patients in remission (morphologic complete remission or morphologic complete remission with incomplete blood count recovery) if safety parameters are met.
Interventions
DRUGVosaroxin and Cytarabine
Sponsors
Hamid Sayar
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 60 years * A diagnosis of AML based on WHO classification (\>20% myeloblasts in peripheral blood or bone marrow) * No previous treatment with chemotherapy for AML, other than hydroxyurea. Previous treatment with hypomethylating agents is acceptable * Patients must have an ECOG (Zubrod) performance status of 0-2 (see Appendix I). * Patients must have adequate hepatic function with a total bilirubin \< 1.5 times upper limit normal (ULN) other than cases of Gilbert disease, and ALT and AST \< 2.5 times ULN; and adequate renal function as defined by a serum creatinine \< 2 times ULN. * Clinically significant nonhematologic toxicity after prior therapy has recovered to grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or newer * Patients must have the ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to initiation of treatment * Left ventricular ejection fraction (LVEF) at least 40% by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)
Exclusion criteria
* Patients with known central nervous system (CNS) leukemia by spinal fluid cytology, flow cytometry or imaging. A lumbar puncture is not required unless CNS involvement is clinically suspected. Patients with signs or symptoms of leukemic meningitis or a history of leukemic meningitis must have a negative lumbar puncture within 2 weeks of study enrollment. * A diagnosis of acute promyelocytic leukemia (APL). The study does not require to rule APL out for every subject. However, if there is clinical suspicion for APL, such diagnosis has to be ruled out before initiation of treatment. * Active malignancy currently undergoing chemo or radiation therapy. Hormone therapy is acceptable. * Active serious infection that at the discretion of treating physician makes patient ineligible for chemotherapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Complete Remission | 2 months | Percentage of patients who have complete remission as defined by the International Working Group for AML: morphologic complete remission (CR) or morphologic complete remission with incomplete blood count recovery (CRi or CRp) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Procedure or Procedure Related Adverse Events | Up to 1 year | Number of unique patients who had a procedure or treatment related (possible, probable or definite) adverse events. (graded per NCI CTC v4.0) |
Countries
United States
Participant flow
Recruitment details
This protocol was based on enrolling 20 patients. Due to the death of 2 patients which raised safety concerns, the study was closed with 2 patients enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Vosaroxin and Cytarabine Each cycle will include vosaroxin treatment on days 1 and 4 (total of 2 days) and cytarabine treatment on days 1-5 (total of 5 days) followed by a variable interval required to achieve hematologic recovery, defined as absolute neutrophil count (ANC) \> 1000 cells/L | 2 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Disease Progression | 1 |
Baseline characteristics
| Characteristic | Vosaroxin and Cytarabine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 72.9 years STANDARD_DEVIATION 1.03 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 2 / 2 |
Outcome results
Primary
Rate of Complete Remission
Percentage of patients who have complete remission as defined by the International Working Group for AML: morphologic complete remission (CR) or morphologic complete remission with incomplete blood count recovery (CRi or CRp)
Time frame: 2 months
Population: All patients receiving at least one dose of study drug and having at least one evaluable post-baseline visit
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vosaroxin and Cytarabine | Rate of Complete Remission | 0 percentage of patients |
Secondary
Procedure or Procedure Related Adverse Events
Number of unique patients who had a procedure or treatment related (possible, probable or definite) adverse events. (graded per NCI CTC v4.0)
Time frame: Up to 1 year
Population: All patients enrolled and received treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vosaroxin and Cytarabine | Procedure or Procedure Related Adverse Events | 1 Participants |