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

• Sponsor: Wake Forest University Health Sciences (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02337478
• Collaborator: National Cancer Institute (NCI) (NIH), Spectrum Pharmaceuticals, Inc (Industry)
• Enrollment: 5
• Location: 1
• Arm: 1
• Actual Duration (Months): 27
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Adult Acute Myeloid Leukemia	Drug: Vincristine Sulfate Liposome; Other: Laboratory Biomarker Analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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.

2. To observe the hematologic improvement-rate of VSLI in this patient population.

SECONDARY OBJECTIVES:

1. 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 Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: Jun 5, 2015
• Actual Primary Completion Date: Mar 31, 2016
• Actual Study Completion Date: Sep 4, 2017

Arms and Interventions

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.	Drug: Vincristine Sulfate Liposome; Given via injection; Other Names: liposomal vincristine Marqibo vincristine liposomal vincristine sulfate liposome injection ; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Number of Participants Able to Complete Two or More Courses of Therapy Regardless of Dose Modifications [Up to 56 days]

Secondary Outcome Measures

1. 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).

2. Overall Survival [Up to 6 months after completion of therapy]

   Kaplan-Meier estimation will be used to analyze overall survival.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157

Sponsors and Collaborators

• Wake Forest University Health Sciences
• National Cancer Institute (NCI)
• Spectrum Pharmaceuticals, Inc

Investigators

• Principal Investigator: Timothy Pardee, Wake Forest University Health Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT02337478
• Other Study ID Numbers: IRB00030674; NCI-2014-02535; CCCWFU 22214; P30CA012197
• First Posted: Jan 13, 2015
• Last Update Posted: Aug 14, 2019
• Last Verified: Jul 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Vincristine

Study Results

Participant Flow

Arm/Group Title	Treatment (Vincristine Sulfate Liposome)
Arm/Group Description	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
Period Title: Overall Study
STARTED	5
COMPLETED	0
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Treatment (Vincristine Sulfate Liposome)
Arm/Group Description	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
Overall Participants	5
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 40%
>=65 years	3 60%
Sex: Female, Male (Count of Participants)
Female	2 40%
Male	3 60%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	5 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	5 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	5 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Able to Complete Two or More Courses of Therapy Regardless of Dose Modifications
Time Frame	Up to 56 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Vincristine Sulfate Liposome)
Arm/Group Description	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
Measure Participants	5
Count of Participants [Participants]	0 0%

2. Secondary Outcome

Title	Response Rate (CR, CRi, PR, and MLFS)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Vincristine Sulfate Liposome)
Arm/Group Description	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
Measure Participants	5
No response	5 100%
Complete response	0 0%
Complete reponse (incomplete)	0 0%
Partial response	0 0%
Morphologic leukemia free state	0 0%

3. Secondary Outcome

Title	Overall Survival
Description	Kaplan-Meier estimation will be used to analyze overall survival.
Time Frame	Up to 6 months after completion of therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Vincristine Sulfate Liposome)
Arm/Group Description	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
Measure Participants	5
Mean (95% Confidence Interval) [months]	1.5

Adverse Events

Time Frame	Over 6 months
Adverse Event Reporting Description	Adverse events were captured for 8 days after the last dose of Vincristine Sulfate Liposome Injection (VSLI). Serious adverse events includes all Grade 5 and unexpected Grade 4 toxicities
Arm/Group Title	Treatment (Vincristine Sulfate Liposome)
Arm/Group Description	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
All Cause Mortality
	Treatment (Vincristine Sulfate Liposome)
	Affected / at Risk (%)	# Events
Total	5/5 (100%)
Serious Adverse Events
	Treatment (Vincristine Sulfate Liposome)
	Affected / at Risk (%)	# Events
Total	5/5 (100%)
General disorders
Death	2/5 (40%)	2
Investigations
Neutrophil count decreased	1/5 (20%)	1
Platelet count decreased	1/5 (20%)	1
White blood cell decreased	1/5 (20%)	1
Metabolism and nutrition disorders
Hyponatremia	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Vincristine Sulfate Liposome)
	Affected / at Risk (%)	# Events
Total	5/5 (100%)
Blood and lymphatic system disorders
Anemia	5/5 (100%)	6
Disseminated intravascular coagulation	4/5 (80%)	4
Cardiac disorders
Atrial fibrillation	1/5 (20%)	1
Cardiac disorders, other	2/5 (40%)	2
Sinus tachycardia	3/5 (60%)	3
Ventricular arrhythmia	1/5 (20%)	1
Eye disorders
Blurred vision	1/5 (20%)	1
Scleral disorder	1/5 (20%)	1
Gastrointestinal disorders
Abdominal distension	2/5 (40%)	2
Abdominal pain	3/5 (60%)	3
Bloating	2/5 (40%)	2
Constipation	4/5 (80%)	4
Diarrhea	2/5 (40%)	2
Dry mouth	2/5 (40%)	2
Dysphagia	1/5 (20%)	1
Esophagitis	1/5 (20%)	1
Gastroesophageal reflux disease	4/5 (80%)	4
Gastrointestinal disorders, other	1/5 (20%)	2
Nausea	5/5 (100%)	5
Vomiting	2/5 (40%)	3
General disorders
Chills	2/5 (40%)	2
Edema limbs	4/5 (80%)	4
Fatigue	4/5 (80%)	4
Fever	1/5 (20%)	1
General disorders and administration site conditions - Other	3/5 (60%)	3
Non-cardiac chest pain	2/5 (40%)	2
Pain	2/5 (40%)	2
Infections and infestations
Catheter related infection	1/5 (20%)	1
Mucosal infection	1/5 (20%)	1
Sepsis	1/5 (20%)	1
Skin infection	1/5 (20%)	1
Injury, poisoning and procedural complications
Bruising	4/5 (80%)	4
Investigations
Activated partial thromboplastin time prolonged	1/5 (20%)	1
Alanine aminotransferase increased	1/5 (20%)	1
Alkaline phosphatase increased	1/5 (20%)	1
Aspartate aminotransferase increased	3/5 (60%)	3
Cardiac troponin I increased	1/5 (20%)	1
Electrocardiogram QT corrected interval prolonged	2/5 (40%)	2
Investigations - other	2/5 (40%)	2
Lymphocyte count decreased	5/5 (100%)	5
Neutrophil count decreased	4/5 (80%)	5
Platelet count decreased	4/5 (80%)	5
White blood cell decreased	4/5 (80%)	5
Metabolism and nutrition disorders
Alkalosis	1/5 (20%)	1
Anorexia	5/5 (100%)	5
Dehydration	1/5 (20%)	1
Hyperglycemia	5/5 (100%)	6
Hypermagnesemia	1/5 (20%)	1
Hyperuricemia	1/5 (20%)	1
Hypoalbuminemia	4/5 (80%)	4
Hypocalcemia	1/5 (20%)	1
Hypokalemia	4/5 (80%)	4
Hypomagnesemia	5/5 (100%)	6
Hyponatremia	3/5 (60%)	4
Hypophosphastemia	1/5 (20%)	1
Weight loss	3/5 (60%)	3
Musculoskeletal and connective tissue disorders
Arthralgia	1/5 (20%)	1
Back pain	2/5 (40%)	2
Generalized muscle weakness	5/5 (100%)	6
Myalgia	1/5 (20%)	1
Pain in extremity	2/5 (40%)	2
Nervous system disorders
Dizziness	3/5 (60%)	3
Headache	2/5 (40%)	2
Lethargy	1/5 (20%)	1
Nervous system disorders Other	1/5 (20%)	2
Peripheral sensory neuropathy	4/5 (80%)	4
Presyncope	1/5 (20%)	1
Psychiatric disorders
Agitation	1/5 (20%)	1
Anxiety	4/5 (80%)	4
Confusion	3/5 (60%)	3
Delirium	1/5 (20%)	1
Depression	1/5 (20%)	1
Insomnia	3/5 (60%)	3
Renal and urinary disorders
Chronic kidney disease	1/5 (20%)	1
Urinary incontinence	1/5 (20%)	1
Reproductive system and breast disorders
Reproductive system and breast disorder - other	1/5 (20%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	3/5 (60%)	3
Epistaxis	1/5 (20%)	1
Hoarseness	1/5 (20%)	1
Pleural effusion	2/5 (40%)	2
Respiratory, thoracic and mediastinal disorder - other	2/5 (40%)	2
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/5 (20%)	1
Skin and subcutaneous tissue disorders - other	3/5 (60%)	3
Vascular disorders
Hot flashes	1/5 (20%)	1
Hypertension	2/5 (40%)	2
Hypotension	1/5 (20%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.