Acute Myeloid Leukemia
Conditions
Keywords
acute myeloid leukemia, high dose cytarabine, HiDAC, consolidation, chemotherapy schedule, bone marrow, elderly
Brief summary
This phase 2, open label, non-randomized study will evaluate the safety of administering high dose cytarabine (HiDAC) consolidation therapy on days 1-3 of each cycle, as compared to standard administration on days 1, 3, and 5 of each cycle, in patients 61 years and older with de novo acute myeloid leukemia (AML).
Interventions
DRUGCytarabine
Subjects on this arm will prospectively receive consolidation therapy with cytarabine. Subjects will be treated with 1000 mg/m2 cytarabine intravenously every 12 hours on Days 1-3 of each consolidation cycle. Subjects will receive up to four consolidation cycles.
Sponsors
University of Florida
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
61 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Both males and females ≥ 61 years of age * A clinical diagnosis of de novo, non-M3 acute myeloid leukemia (AML) confirmed by greater than 20% blasts in peripheral blood or on diagnostic bone marrow biopsy who have completed intensive induction chemotherapy and are confirmed in complete remission #1 (defined by \< 5% myeloblasts on recovery bone marrow biopsy, Absolute neutrophil count \> 1000/uL and platelets \> 100x103/uL) and able to receive HiDAC consolidation #1 * Patients on the prospective arm must be willing to have labs/clinic visits at UF Health Shands approximately every 48 hours +/- 24 hours after discharge from chemotherapy admission to be included. If prospective subjects cannot be followed at the UF site then telephone visits are allowed to follow for toxicity and transfusions. Records can be requested from subject's local physician office. * Written informed consent obtained from the subject and the subject agrees to comply with all the study-related procedures. For subjects on the historical arm, there will be a waiver of informed consent (as these patients may be deceased or not be available for retrospective consent).
Exclusion criteria
* Age \< 61 years * Patients unable to provide informed consent for prospective arm * Secondary AML (documented history of antecedent hematological disorder, such as myelodysplastic syndrome or therapy-related AML) or chronic myeloid leukemia (CML) in blast crisis * Patients receiving, received, or who will receive a FLT3 inhibitor * Patients receiving, received, or who will receive an IDH1 or IDH2 inhibitor * Serum creatinine greater than 2 mg/dL * History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician * Prisoners or subjects who are involuntarily incarcerated, or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness * For historical arm, subjects will be excluded if adequate data is not available in electronic medical record (e.g., if patient was followed by their local oncologist between chemotherapy cycles and labs/transfusions/clinic notes, etc. are not available) * Karnofsky performance status of 40 or less at study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Neutropenia | 5 months | Determine the duration of neutropenia in older patients with de novo AML after consolidation chemotherapy with HiDAC 123, as compared to historical controls treated with HiDAC 135. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Thrombocytopenia | 5 months | Determine the duration of thrombocytopenia in older patients with de novo AML after consolidation chemotherapy with HiDAC 123, as compared to historical controls treated with HiDAC 135. |
| Incidence of Documented Infections | 5 months | Compare the incidence of documented infections (bloodstream infection, pneumonia, invasive fungal infection, Clostridium difficile infection, typhlitis, and febrile neutropenia) in patients receiving HiDAC 123 and HiDAC 135. |
| Number of Transfusions | 4 months | Compare the number of red blood cell and platelet transfusions per cycle in patients receiving HiDAC 123 and HiDAC 135. |
| Readmission Rates and Length of Readmission Stay | 5 months | Compare the incidence of readmission and the length of readmission stay in patients receiving HiDAC 123 and HiDAC 135. |
| Time to Next Treatment | 5 months | Compare the time to next treatment (next chemotherapy cycle, transplant, etc.) in patients receiving HiDAC 123 and HiDAC 135. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prospective HiDAC Treatment (HiDAC 123) Subject on this arm will be treated with HiDAC prospectively.
Cytarabine: Subjects on this arm will prospectively receive consolidation therapy with cytarabine. Subjects will be treated with 1000 mg/m2 cytarabine intravenously every 12 hours on Days 1-3 of each consolidation cycle. Subjects will receive up to four consolidation cycles. | 5 |
| Historical HiDAC Treatment (HiDAC 135) Subjects on this arm will be historical controls who have previously received treatment with HiDAC.
Cytarabine: Subjects on this arm will have received consolidation therapy with cytarabine between 2/1/2017 and 2/1/2019. Subjects will have received 1000 mg/m2 cytarabine intravenously every 12 hours on days 1, 3, and 5 of each consolidation cycle and will have received up to 4 consolidation cycles. | 0 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study termination | 3 | 0 |
Baseline characteristics
| Characteristic | Historical HiDAC Treatment (HiDAC 135) | Total | Prospective HiDAC Treatment (HiDAC 123) |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 4 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Continuous | — | 66.8 years | 66.8 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | — | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | — | 5 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | — | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | — | 4 Participants | 4 Participants |
| Region of Enrollment United States | — | 5 participants | 5 participants |
| Sex: Female, Male Female | — | 4 Participants | 4 Participants |
| Sex: Female, Male Male | — | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 5 | 0 / 0 |
| other Total, other adverse events | 5 / 5 | 0 / 0 |
| serious Total, serious adverse events | 4 / 5 | 0 / 0 |
Outcome results
Primary
Duration of Neutropenia
Determine the duration of neutropenia in older patients with de novo AML after consolidation chemotherapy with HiDAC 123, as compared to historical controls treated with HiDAC 135.
Time frame: 5 months
Population: Data were not collected for subjects on either arm. No subjects were enrolled on the historical control arm.
Secondary
Duration of Thrombocytopenia
Determine the duration of thrombocytopenia in older patients with de novo AML after consolidation chemotherapy with HiDAC 123, as compared to historical controls treated with HiDAC 135.
Time frame: 5 months
Population: Data were not collected for subjects on either arm. No subjects were enrolled on the historical control arm.
Secondary
Incidence of Documented Infections
Compare the incidence of documented infections (bloodstream infection, pneumonia, invasive fungal infection, Clostridium difficile infection, typhlitis, and febrile neutropenia) in patients receiving HiDAC 123 and HiDAC 135.
Time frame: 5 months
Population: Data were not collected for subjects on either arm. No subjects were enrolled on the historical control arm.
Secondary
Number of Transfusions
Compare the number of red blood cell and platelet transfusions per cycle in patients receiving HiDAC 123 and HiDAC 135.
Time frame: 4 months
Population: Data were not collected for subjects on either arm. No subjects were enrolled on the historical control arm.
Secondary
Readmission Rates and Length of Readmission Stay
Compare the incidence of readmission and the length of readmission stay in patients receiving HiDAC 123 and HiDAC 135.
Time frame: 5 months
Population: Data were not collected for subjects on either arm. No subjects were enrolled on the historical control arm.
Secondary
Time to Next Treatment
Compare the time to next treatment (next chemotherapy cycle, transplant, etc.) in patients receiving HiDAC 123 and HiDAC 135.
Time frame: 5 months
Population: Data were not collected for subjects on either arm. No subjects were enrolled on the historical control arm.