Phase 1/2 Study of VSLI Plus Rituximab in Patients With Relapsed and/or Refractory NHL

December 31, 2019 updated by: Acrotech Biopharma Inc.

A Phase I/II Study of Rituximab Plus Vincristine Sulfate Liposomes Injection in the Treatment of Relapsed or Refractory Aggressive Non Hodgkin's Lymphoma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • West Yorkshire
      • Leeds, West Yorkshire, United Kingdom, LS1 3EX
        • Leeds General Infirmary
  • United States
    • California
      • San Francisco, California, United States, 94110
        • University of California

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • 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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: VSLI plus rituximab
VSLI (vincristine sulfate liposome injection) plus rituximab
Drug: Vincristine Sulfate Liposome Injection plus rituximab
Other Names:
  • rituxan
  • Marqibo
  • rituximab
  • VSLI

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate
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).
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).
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 Measures

Outcome Measure
Measure Description
Time Frame
Assessment of the number of events and number and percentage of patients with treatment-emergent AEs
Time Frame: AEs were assessed up to 30 days post last dose. Dosing may last up to 24 weeks.

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
AEs were assessed up to 30 days post last dose. Dosing may last up to 24 weeks.
Time to Progression
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.
Time To Progression (TTP), defined as the interval between the initial day of dosing and disease progression or death due to NHL
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.
Overall survival
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
Overall Survival (OS) was defined as the interval between the initial day of dosing and death due to any cause.
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Acrotech Biopharma Inc.

Investigators

  • Principal Investigator: Lawrence Kaplan, MD, University of California, San Francisco
  • Principal Investigator: Gareth Morgan, Prof., Leeds General Infirmary

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2001

Primary Completion (Actual)

April 1, 2004

Study Completion (Actual)

April 1, 2005

Study Registration Dates

First Submitted

April 29, 2013

First Submitted That Met QC Criteria

May 7, 2013

First Posted (Estimate)

May 10, 2013

Study Record Updates

Last Update Posted (Actual)

January 3, 2020

Last Update Submitted That Met QC Criteria

December 31, 2019

Last Verified

December 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA00005

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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