Recurrent Adult Acute Myeloid Leukemia
Conditions
Brief summary
This pilot phase II trial studies how well vincristine sulfate liposome works in treating patients with acute myeloid leukemia that has returned after a period of improvement or has not responded to previous treatment. Drugs used in chemotherapy, such as vincristine sulfate liposome, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Liposomal encapsulation prolongs bioavailability (proportion of drug that enters the circulation when introduced into the body) of vincristine sulfate, and may increase its delivery to cancer cells with fewer side effects.
Detailed description
PRIMARY OBJECTIVES: I. To determine the feasibility of administering vincristine sulfate liposome injection (VSLI) to relapsed or refractory acute myeloid leukemia (AML) patients having failed, refused or not a candidate for at least one chemotherapy salvage regimen. II. To observe the hematologic improvement-rate of VSLI in this patient population. SECONDARY OBJECTIVES: I. To observe the overall survival of patients treated with VSLI. II. To observe the response rate (complete remission \[CR\], complete remission with incomplete count recovery \[CRi\], partial response \[PR\], and morphologic leukemia free state \[MLFS\]) of VSLI in this patient population. OUTLINE: Patients receive vincristine sulfate liposome via injection on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for up to 6 months.
Interventions
Given via injection
OTHERLaboratory Biomarker Analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Spectrum Pharmaceuticals, Inc
Wake Forest University Health Sciences
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
* Patients must have histologically or cytologically documented relapsed and/or refractory acute myeloid leukemia * Patients must be ineligible for, refused or having failed at least one previous salvage regimen * Eastern Cooperative Oncology Group (ECOG) performance status of =\< 3 * Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted contraceptive methods (abstinence, intrauterine device \[IUD\], oral contraceptive or double barrier device), and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation * Fertile men must practice effective contraceptive methods during the study period, unless documentation of infertility exists * Mentally competent, ability to understand and willingness to sign the informed consent form * No serious medical illness that would potentially increase patients' risk for toxicity * No active central nervous system (CNS) disease * No active uncontrolled bleeding/bleeding diathesis * No condition or abnormality which may, in the opinion of the investigator, compromise the safety of the patient * No unwillingness or inability to follow protocol requirements * No evidence of ongoing, uncontrolled infection * No requirement for immediate palliative treatment of any kind including surgery * No option for immediate bone marrow transplant unless patient refuses this therapy * Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) =\< 3 x upper normal limit (UNL), alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =\< 3 x UNL * Bilirubin =\< 3 x UNL * Glomerular filtration rate (GFR) \> 50 ml/min/1.72 m\^2 or creatinine \< 2 g/dL
Exclusion criteria
* Serious medical illness or severe debilitating pulmonary disease that would potentially increase the patients' risk for toxicity * Patients with persistent grade 3 or higher prior vincristine (VCR) (vincristine sulfate)-related neuropathy * Patients with active central nervous system (CNS) disease * Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease) * Pregnant women, or women of child-bearing potential not using reliable means of contraception * Lactating females * Fertile men unwilling to practice contraceptive methods during the study period * Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients * Unwilling or unable to follow protocol requirements * Evidence of ongoing, uncontrolled infection * Patients with known human immunodeficiency virus (HIV) infection * Requirement for immediate palliative treatment of any kind including surgery * Evidence of inadequate hepatic function (aspartate aminotransferase \[AST/SGOT\] =\< 3 x upper normal limit \[UNL\], alanine aminotransferase \[ALT/SGPT\] =\< 3 x UNL \[=\< 5 x ULN if liver metastases present\], bilirubin =\< 1.5 x UNL) * Evidence of inadequate renal function (creatinine \> 2 g/dL)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Able to Complete Two or More Courses of Therapy Regardless of Dose Modifications | Up to 56 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (CR, CRi, PR, and MLFS) | Up to 6 months after completion of study treatment | Confidence intervals will be calculated around the estimates of the response rate (CR, CRi, PR, and MLFS) of VSLI. Assuming a response rate of 0.1, with 39 participants, 95 percent confidence intervals with a 0.09 margin of error (0.01, 0.19) or a margin of error of 0.16 around a response rate of 0.5 will be created. (Complete remission (CR) bone marrow blasts \<5%, absence of blasts with Auer rods; absence of extramedullary disease, absolute neutrophil count \>1,000, platelet count \>100,000, independence of red cell transfusions; Complete remission with incomplete recovery (CRi) all complete remission except for residual neutropenia or thrombocytopenia; partial remission (PR), decrease of bone marrow blast to 5-25%, decrease of pre-treatment bone marrow blast by at least 50%; morphologic leukemia-free state (MLFS) Bone marrow blasts \<5%, absence of Aeur rods, absence of extramedullary disease, no hematologic recovery required). |
| Overall Survival | Up to 6 months after completion of therapy | Kaplan-Meier estimation will be used to analyze overall survival. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Vincristine Sulfate Liposome) Patients receive vincristine sulfate liposome via injection on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Vincristine Sulfate Liposome: Given via injection
Laboratory Biomarker Analysis: Correlative studies | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 5 |
Baseline characteristics
| Characteristic | Treatment (Vincristine Sulfate Liposome) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 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 | 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 | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 5 |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 5 / 5 |
Outcome results
Primary
Number of Participants Able to Complete Two or More Courses of Therapy Regardless of Dose Modifications
Time frame: Up to 56 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Vincristine Sulfate Liposome) | Number of Participants Able to Complete Two or More Courses of Therapy Regardless of Dose Modifications | 0 Participants |
Secondary
Overall Survival
Kaplan-Meier estimation will be used to analyze overall survival.
Time frame: Up to 6 months after completion of therapy
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment (Vincristine Sulfate Liposome) | Overall Survival | 1.5 months |
Secondary
Response Rate (CR, CRi, PR, and MLFS)
Confidence intervals will be calculated around the estimates of the response rate (CR, CRi, PR, and MLFS) of VSLI. Assuming a response rate of 0.1, with 39 participants, 95 percent confidence intervals with a 0.09 margin of error (0.01, 0.19) or a margin of error of 0.16 around a response rate of 0.5 will be created. (Complete remission (CR) bone marrow blasts \<5%, absence of blasts with Auer rods; absence of extramedullary disease, absolute neutrophil count \>1,000, platelet count \>100,000, independence of red cell transfusions; Complete remission with incomplete recovery (CRi) all complete remission except for residual neutropenia or thrombocytopenia; partial remission (PR), decrease of bone marrow blast to 5-25%, decrease of pre-treatment bone marrow blast by at least 50%; morphologic leukemia-free state (MLFS) Bone marrow blasts \<5%, absence of Aeur rods, absence of extramedullary disease, no hematologic recovery required).
Time frame: Up to 6 months after completion of study treatment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Vincristine Sulfate Liposome) | Response Rate (CR, CRi, PR, and MLFS) | Partial response | 0 Participants |
| Treatment (Vincristine Sulfate Liposome) | Response Rate (CR, CRi, PR, and MLFS) | No response | 5 Participants |
| Treatment (Vincristine Sulfate Liposome) | Response Rate (CR, CRi, PR, and MLFS) | Complete response | 0 Participants |
| Treatment (Vincristine Sulfate Liposome) | Response Rate (CR, CRi, PR, and MLFS) | Complete reponse (incomplete) | 0 Participants |
| Treatment (Vincristine Sulfate Liposome) | Response Rate (CR, CRi, PR, and MLFS) | Morphologic leukemia free state | 0 Participants |