Acute Myelogenous Leukemia (AML)
Conditions
Brief summary
The purpose of this pilot study is to assess the safety and tolerability of omacetaxine for consolidation in patients age 55 and older with acute myelogenous leukemia (AML) in first complete remission following induction with cytarabine and an anthracycline, and also to assess the safety and tolerability of omacetaxine for maintenance in patients age 55 and older with acute AML in first complete remission following 3 consolidation courses with omacetaxine.
Interventions
DRUGOmacetaxine
Omacetaxine 1.25 mg/m² sub-cutaneously twice daily for 5 consecutive days every 28 (± 8) days for 3 cycles. Patients in continuous remission after 3 cycles of consolidation will receive maintenance omacetaxine 1.25 mg/m² twice daily for 3 days, every 28 days for up to 6 cycles
Sponsors
Teva Pharmaceuticals USA
Emory University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of AML including de novo, secondary, or with an antecedent hematologic disorder (AHD) according to the World Health Organization (WHO) criteria. 2. Age ≥ 55 years. 3. Patient eligible for standard induction chemotherapy based on Eastern Cooperative Oncology Group (ECOG) performance status and vital organ function at the discretion of the treating physician. 4. Patients who received 1-2 cycles of hypomethylating therapy (decitabine azacitidine) are eligible. 5. Provide signed written informed consent. 6. Be able to comply with study procedures and follow-up examinations. 7. Be non-fertile or agree to use birth control during the study through the end of last treatment visit. 8. Adequate renal and hepatic function at the time of second registration: * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN); and * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN; and * Serum creatinine ≤ 1.2 x ULN. 9. ECOG performance ≤ 2 at the time of second registration. 10. Patients with a history of carcinoma in remission, on no therapy or on hormonal therapy for the adjuvant treatment of breast carcinoma or prostate carcinoma are included in the study.
Exclusion criteria
1. Diagnosis of acute promyelocytic leukemia (APL, French-American-British \[FAB\] classification M3 or WHO classification of APL with t (15;17)(q22;q12), (PML/retinoic acid receptor alpha \[RARa\] and variants). 2. Prior treatment with omacetaxine. 3. Relapsed or refractory AML. 4. Investigational agent received within 30 days prior to the first dose of study drug. If received any investigational agent prior to this time point, drug-related toxicities must have recovered to Grade 2 or less prior to first dose of study drug. 5. Psychiatric disorders that would interfere with consent, study participation, or follow-up. 6. Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment). 7. Any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo the proposed therapy. This includes uncontrolled hypertension and uncontrolled diabetes, as cases of life threatening hyperglycemia have been reported (using continuous infusion at higher doses of omacetaxine). 8. Active carcinoma requiring systemic chemotherapy or radiation therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Status Assessment Prior to Each Consolidation Cycle | 14 days | Disease status will be assessed by a bone marrow aspirate and biopsy prior to each of 3 consolidation cycles (to ensure that patients are still in remission). |
| Assessment of Disease Status | 1 month | Bone marrow biopsy and aspirate will be obtained. |
| Bone Marrow Aspirate to Confirm Continuous Remission | 3 months | Bone marrow aspirate to confirm continuous remission will be obtained before starting maintenance and at 3 and 6 months from the start of maintenance. |
| Maintenance Toxicities | 24 weeks | Toxicities will be monitored by history, physical examination, and laboratory monitoring during maintenance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Consolidation Toxicities | 12 weeks | Toxicities will be monitored by history, physical examination, and laboratory monitoring (CBC, serum chemistries to include renal and liver function tests) obtained weekly during consolidation and monthly during maintenance according to standard of care (Appendices C and D). Toxicity will be assessed according to the NCI Common Toxicity Criteria Version 4.0 (available at the NCI web site http://ctep.cancer.gov/reporting/ctc.html). |
Countries
United States
Participant flow
Recruitment details
Patients were enrolled between 5/8/2013 and 7/23/2018 at Winship Cancer Institute of Emory University.
Participants by arm
| Arm | Count |
|---|---|
| Omacetaxine: Consolidation/Maintenance Omacetaxine: Omacetaxine 1.25 mg/m² sub-cutaneously twice daily for 5 consecutive days every 28 (± 8) days for 3 cycles.
Patients in continuous remission after 3 cycles of consolidation will receive maintenance omacetaxine 1.25 mg/m² twice daily for 3 days, every 28 days for up to 6 cycles | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | AML (Acute Myelogenous Leukemia) Relapse | 1 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Removed for Transplantation | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Omacetaxine: Consolidation/Maintenance |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 7 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 1 / 7 |
| serious Total, serious adverse events | 1 / 7 |
Outcome results
Primary
Assessment of Disease Status
Bone marrow biopsy and aspirate will be obtained.
Time frame: 1 month
Population: Seven patients completed at least one cycle of omacetaxine.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Omacetaxine: Consolidation/Maintenance | Assessment of Disease Status | Relapsed AML | 1 Participants |
| Omacetaxine: Consolidation/Maintenance | Assessment of Disease Status | Remission | 6 Participants |
Primary
Bone Marrow Aspirate to Confirm Continuous Remission
Bone marrow aspirate to confirm continuous remission will be obtained before starting maintenance and at 3 and 6 months from the start of maintenance.
Time frame: 3 months
Population: No patients entered the maintenance phase of this study.
Primary
Disease Status Assessment Prior to Each Consolidation Cycle
Disease status will be assessed by a bone marrow aspirate and biopsy prior to each of 3 consolidation cycles (to ensure that patients are still in remission).
Time frame: 14 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Omacetaxine: Consolidation/Maintenance | Disease Status Assessment Prior to Each Consolidation Cycle | Relapsed AML | 0 Participants |
| Omacetaxine: Consolidation/Maintenance | Disease Status Assessment Prior to Each Consolidation Cycle | Remission | 7 Participants |
Primary
Maintenance Toxicities
Toxicities will be monitored by history, physical examination, and laboratory monitoring during maintenance.
Time frame: 24 weeks
Population: No patients entered the maintenance phase of this study.
Secondary
Consolidation Toxicities
Toxicities will be monitored by history, physical examination, and laboratory monitoring (CBC, serum chemistries to include renal and liver function tests) obtained weekly during consolidation and monthly during maintenance according to standard of care (Appendices C and D). Toxicity will be assessed according to the NCI Common Toxicity Criteria Version 4.0 (available at the NCI web site http://ctep.cancer.gov/reporting/ctc.html).
Time frame: 12 weeks
Population: Two participants experienced toxicities: thrombocytopenia and atrial flutter.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Omacetaxine: Consolidation/Maintenance | Consolidation Toxicities | No Toxicities | 5 Participants |
| Omacetaxine: Consolidation/Maintenance | Consolidation Toxicities | Thrombocytopenia | 1 Participants |
| Omacetaxine: Consolidation/Maintenance | Consolidation Toxicities | Atrial Flutter | 1 Participants |