Back to resultsPhase 1/2 Study of VSLI Plus Rituximab in Patients With Relapsed and/or Refractory NHL
Primary Purpose
Non-Hodgkin's Lymphoma, Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Vincristine Sulfate Liposome Injection plus rituximab
Sponsored by
About this trial
This is an interventional treatment trial for Non-Hodgkin's Lymphoma focused on measuring NHL, non-Hodgkin's lymphoma, diffuse large b-cell lymphoma, mantle cell lymphoma
Eligibility Criteria
Inclusion Criteria:
Histologically-confirmed diffuse large B-cell non-Hodgkin's lymphoma (NHL), as defined by the Revised European American Lymphoma/WHO classification. This included: diffuse large B-cell, primary mediastinal large B-cell lymphoma with sclerosis,intravascular large B-cell lymphoma, immunoblastic B-cell lymphoma, T-cell rich B-cell lymphoma or anaplastic large B-cell lymphoma. In the US protocol only, patients who had transformation from an indolent lymphoma and those who had mantle cell lymphoma were eligible.
- Confirmation of CD20 expression on lymphoma cells.
- Eastern Cooperative Oncology Group (ECOG) ≤2.
- One or more prior chemotherapy regimens. Patients who had received prior rituximab therapy as part of an induction chemotherapy regimen or who had a previous response to rituximab as a single agent were eligible.
- Measurable disease in at least 1 site, which had not been previously irradiated.
Measurable disease was defined as at least 1 bidimensionally measurable lesion with clearly defined margins that were ≥1.5 cm in the largest dimension determined by physical examination or computed tomography (CT) scan.
- Total bilirubin and serum creatinine ≤2 times the ULN.
- Absolute neutrophil count (ANC) ≥0.5 × 109/L, and platelets ≥50 × 109/L.
- 18 years of age or older.
- Women of childbearing potential who were willing to use an acceptable method of contraception throughout the course of the study.
Signed and dated informed consent form.
Exclusion Criteria:
- Known transformation from an indolent lymphoma (UK protocol only).
- Eligible for conventional or high-dose chemotherapy with curative intent.
- Radiotherapy, chemotherapy, immunotherapy, or corticosteroids (>10 mg/day of prednisone or equivalent) within the past 4 weeks.
- Any previous malignancies with less than a 5-year complete remission interval, except for curatively resected basal cell carcinoma or curatively resected in situ carcinoma of the uterine cervix.
- History of or active CNS-lymphoma, AIDS-related lymphoma, or any uncontrolled severe medical illness or infection.
- History of neurologic disorders unrelated to chemotherapy (including familial neurologic diseases and acquired demyelinating disorders).
- Grade 3 or 4 sensory or motor neuropathy at screening related to prior chemotherapy.
- Major surgery (excluding that for diagnosis) within 4 weeks of enrollment.
- Pregnant or lactating women (women of childbearing potential underwent a pregnancy test).
- Allergy to vincristine, or other vinca alkaloids.
- Progressive disease while receiving or within 1 month of having received previous rituximab therapy (US protocol only).
- Hypersensitivity to any component of rituximab or to murine proteins (UK protocol only).
Sites / Locations
- University of California
- Leeds General Infirmary
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
VSLI plus rituximab
Arm Description
VSLI (vincristine sulfate liposome injection) plus rituximab
Outcomes
Primary Outcome Measures
Objective response rate
The primary efficacy endpoint was the objective response rate (ORR) defined as the proportion of patients whose best responses were complete response (CR) and partial response (PR) (ORR = CR + PR).
Secondary Outcome Measures
Assessment of the number of events and number and percentage of patients with treatment-emergent AEs
The number of events and number and percentage of patients with treatment-emergent AEs that occurred from the time of first study treatment up to 30 days following the last study treatment were summarized by MedDRA system organ class and preferred term, NCI CTC grade, and relationship to study drug.
Safety variables included adverse events, neurologic assessments, chemistry and hematology laboratory tests, physical examinations, and vital signs.
Neurologic symptom scores were summarized for baseline and worst score on study. The number and percentage of patients with neurologic symptom abnormalities were tabulated and presented by severity and cycle for each symptom.
Neurologic sign scores were summarized for baseline and worst score on study. The number and percentage of patients with neurologic sign abnormalities were tabulated and presented by severity and cycle for each sign.
Shifts from baseline to worst value were tabulated by cycle based on NCI CTC grades
Time to Progression
Time To Progression (TTP), defined as the interval between the initial day of dosing and disease progression or death due to NHL
Overall survival
Overall Survival (OS) was defined as the interval between the initial day of dosing and death due to any cause.
Full Information
NCT ID
NCT01851551
First Posted
April 29, 2013
Last Updated
December 31, 2019
Sponsor
Acrotech Biopharma Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01851551
Brief Title
Phase 1/2 Study of VSLI Plus Rituximab in Patients With Relapsed and/or Refractory NHL
Official Title
A Phase I/II Study of Rituximab Plus Vincristine Sulfate Liposomes Injection in the Treatment of Relapsed or Refractory Aggressive Non Hodgkin's Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
September 2001 (undefined)
Primary Completion Date
April 2004 (Actual)
Study Completion Date
April 2005 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Acrotech Biopharma Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This was a Phase 1/2 study performed at two clinical centers in the US and UK. It was a single arm, open label study evaluating VSLI plus rituximab in adults with aggressive relapsed or refractory non-Hodgkin's lymphoma.
Detailed Description
The primary efficacy endpoint was objective response rate, defined as the proportion of patients with a response of CR + PR.
Duration of response, time to progression, and overall survival were analyzed. Descriptive statistics were used for demographics, disease characteristics, treatment exposures, efficacy, and safety variables.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkin's Lymphoma, Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma
Keywords
NHL, non-Hodgkin's lymphoma, diffuse large b-cell lymphoma, mantle cell lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
VSLI plus rituximab
Arm Type
Experimental
Arm Description
VSLI (vincristine sulfate liposome injection) plus rituximab
Intervention Type
Drug
Intervention Name(s)
Vincristine Sulfate Liposome Injection plus rituximab
Other Intervention Name(s)
Marqibo, VSLI, rituximab, rituxan
Primary Outcome Measure Information:
Title
Objective response rate
Description
The primary efficacy endpoint was the objective response rate (ORR) defined as the proportion of patients whose best responses were complete response (CR) and partial response (PR) (ORR = CR + PR).
Time Frame
Assessed prior to each cycle for up to 12 cycles (24 weeks). For patients achieving a complete or partial response, follow-up assessments were to be made 2, 8, 16, and 24 weeks after treatment was discontinued (up to ~48 wks).
Secondary Outcome Measure Information:
Title
Assessment of the number of events and number and percentage of patients with treatment-emergent AEs
Description
The number of events and number and percentage of patients with treatment-emergent AEs that occurred from the time of first study treatment up to 30 days following the last study treatment were summarized by MedDRA system organ class and preferred term, NCI CTC grade, and relationship to study drug.
Safety variables included adverse events, neurologic assessments, chemistry and hematology laboratory tests, physical examinations, and vital signs.
Neurologic symptom scores were summarized for baseline and worst score on study. The number and percentage of patients with neurologic symptom abnormalities were tabulated and presented by severity and cycle for each symptom.
Neurologic sign scores were summarized for baseline and worst score on study. The number and percentage of patients with neurologic sign abnormalities were tabulated and presented by severity and cycle for each sign.
Shifts from baseline to worst value were tabulated by cycle based on NCI CTC grades
Time Frame
AEs were assessed up to 30 days post last dose. Dosing may last up to 24 weeks.
Title
Time to Progression
Description
Time To Progression (TTP), defined as the interval between the initial day of dosing and disease progression or death due to NHL
Time Frame
First dose to disease progression. Follow up was reported approximately every 3 months post-dose up to the date of patient death. Patients were followed up to 2 yrs.
Title
Overall survival
Description
Overall Survival (OS) was defined as the interval between the initial day of dosing and death due to any cause.
Time Frame
The interval between first dose and death due to any cause. Reported every 3 months post dose up to patient death. Follow up was approximately 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically-confirmed diffuse large B-cell non-Hodgkin's lymphoma (NHL), as defined by the Revised European American Lymphoma/WHO classification. This included: diffuse large B-cell, primary mediastinal large B-cell lymphoma with sclerosis,intravascular large B-cell lymphoma, immunoblastic B-cell lymphoma, T-cell rich B-cell lymphoma or anaplastic large B-cell lymphoma. In the US protocol only, patients who had transformation from an indolent lymphoma and those who had mantle cell lymphoma were eligible.
Confirmation of CD20 expression on lymphoma cells.
Eastern Cooperative Oncology Group (ECOG) ≤2.
One or more prior chemotherapy regimens. Patients who had received prior rituximab therapy as part of an induction chemotherapy regimen or who had a previous response to rituximab as a single agent were eligible.
Measurable disease in at least 1 site, which had not been previously irradiated.
Measurable disease was defined as at least 1 bidimensionally measurable lesion with clearly defined margins that were ≥1.5 cm in the largest dimension determined by physical examination or computed tomography (CT) scan.
Total bilirubin and serum creatinine ≤2 times the ULN.
Absolute neutrophil count (ANC) ≥0.5 × 109/L, and platelets ≥50 × 109/L.
18 years of age or older.
Women of childbearing potential who were willing to use an acceptable method of contraception throughout the course of the study.
Signed and dated informed consent form.
Exclusion Criteria:
Known transformation from an indolent lymphoma (UK protocol only).
Eligible for conventional or high-dose chemotherapy with curative intent.
Radiotherapy, chemotherapy, immunotherapy, or corticosteroids (>10 mg/day of prednisone or equivalent) within the past 4 weeks.
Any previous malignancies with less than a 5-year complete remission interval, except for curatively resected basal cell carcinoma or curatively resected in situ carcinoma of the uterine cervix.
History of or active CNS-lymphoma, AIDS-related lymphoma, or any uncontrolled severe medical illness or infection.
History of neurologic disorders unrelated to chemotherapy (including familial neurologic diseases and acquired demyelinating disorders).
Grade 3 or 4 sensory or motor neuropathy at screening related to prior chemotherapy.
Major surgery (excluding that for diagnosis) within 4 weeks of enrollment.
Pregnant or lactating women (women of childbearing potential underwent a pregnancy test).
Allergy to vincristine, or other vinca alkaloids.
Progressive disease while receiving or within 1 month of having received previous rituximab therapy (US protocol only).
Hypersensitivity to any component of rituximab or to murine proteins (UK protocol only).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lawrence Kaplan, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Gareth Morgan, Prof.
Organizational Affiliation
Leeds General Infirmary
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Facility Name
Leeds General Infirmary
City
Leeds
State/Province
West Yorkshire
ZIP/Postal Code
LS1 3EX
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Phase 1/2 Study of VSLI Plus Rituximab in Patients With Relapsed and/or Refractory NHL
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