Clinical trial NCT01851551: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: Acrotech Biopharma Inc.
Sponsor class: INDUSTRY
First posted: 2013-05-10
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Objective response rate
timeFrame: 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 outcomes:
measure: Assessment of the number of events and number and percentage of patients with treatment-emergent AEs
timeFrame: AEs were assessed up to 30 days post last dose. Dosing may last up to 24 weeks.
measure: Time to Progression
timeFrame: 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.
measure: Overall survival
timeFrame: 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
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California
state: California
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
state: West Yorkshire
Study officials:
affiliation: University of California, San Francisco
name: Lawrence Kaplan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Leeds General Infirmary
name: Gareth Morgan, Prof.
role: PRINCIPAL_INVESTIGATOR
References: