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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Recurrent Adult Acute Myeloid Leukemia
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Vincristine Sulfate Liposome

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Vincristine Sulfate Liposome; Given via injection; Other Names: liposomal vincristine; Marqibo; vincristine liposomal; vincristine sulfate liposome injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI); Spectrum Pharmaceuticals, Inc
• Investigators: Principal Investigator: Timothy Pardee, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2015
• Primary Completion (Actual): March 31, 2016
• Study Completion (Actual): September 4, 2017

Study Registration Dates

• First Submitted: January 9, 2015
• First Submitted That Met QC Criteria: January 9, 2015
• First Posted (Estimate): January 13, 2015

Study Record Updates

• Last Update Posted (Actual): August 14, 2019
• Last Update Submitted That Met QC Criteria: July 31, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Vincristine
• Other Study ID Numbers: IRB00030674; P30CA012197 (U.S. NIH Grant/Contract); NCI-2014-02535 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CCCWFU 22214 (Other Identifier: Wake Forest University Health Sciences)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No