Vincristine Sulfate Liposome in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Open Label, Phase II Study of the Feasibility and Efficacy of Vincristine Sulfate Liposome Injection in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)

Conditions
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Recurrent Adult Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Vincristine Sulfate Liposome
* Other: Laboratory Biomarker Analysis


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (vincristine sulfate liposome)<br>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. | Drug: Vincristine Sulfate Liposome<br>* Given via injection<br>* Other names: vincristine sulfate liposome injection;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Able to Complete Two or More Courses of Therapy Regardless of Dose Modifications |  | Up to 56 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Up to 6 months after completion of study treatment | 
| Overall Survival | Kaplan-Meier estimation will be used to analyze overall survival. | Up to 6 months after completion of therapy |