NCT02257242

Brief Summary

This study evaluates addition of Vincristine Sulfate Liposome Injection (Marqibo®) to the standard regimen of Bendamustine and Rituximab in adult patients with indolent B-cell lymphoma. This is a dose-escalation study.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
11

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started May 2017

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 30, 2014

Completed
6 days until next milestone

First Posted

Study publicly available on registry

October 6, 2014

Completed
2.6 years until next milestone

Study Start

First participant enrolled

May 10, 2017

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 22, 2020

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 18, 2020

Completed
2.2 years until next milestone

Results Posted

Study results publicly available

February 9, 2023

Completed
Last Updated

February 9, 2023

Status Verified

May 1, 2022

Enrollment Period

3.3 years

First QC Date

September 30, 2014

Results QC Date

November 4, 2021

Last Update Submit

May 12, 2022

Conditions

Lymphoma, Non-HodgkinLymphoma, FollicularLymphoma, Mantle-CellLymphoma, Small-CellWaldenstrom MacroglobulinemiaLymphoma, B-Cell, Marginal Zone

Keywords

BendamustineRituximabVincristine sulfateVincristine sulfate liposome injectionPhase IEscalation With Overdose Control

Outcome Measures

Primary Outcomes (1)

  • Maximum Tolerated Dose

    Determined as the median of the marginal posterior distribution using data from all available patients

    Up to 6 cycles of treatment (approximately 6 months)

Secondary Outcomes (3)

  • Number of Participants Who Completed Six Cycles of Study Treatment

    Up to 6 cycles of treatment (approximately 6 months)

  • Response Rate

    Up to 6 cycles of treatment (approximately 6 months)

  • Complete Response Rate

    Up to 6 cycles of treatment (approximately 6 months)

Study Arms (9)

Vincristine sulfate liposome injection 1.8 mg/m^2

EXPERIMENTAL

Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.

Drug: RituximabDrug: BendamustineDrug: Vincristine sulfate liposome injection

Vincristine sulfate liposome injection 1.95 mg/m^2

EXPERIMENTAL

Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.

Drug: RituximabDrug: BendamustineDrug: Vincristine sulfate liposome injection

Vincristine sulfate liposome injection 1.98 mg/m^2

EXPERIMENTAL

Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.

Drug: RituximabDrug: BendamustineDrug: Vincristine sulfate liposome injection

Vincristine sulfate liposome injection 2.04 mg/m^2

EXPERIMENTAL

Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.

Drug: RituximabDrug: BendamustineDrug: Vincristine sulfate liposome injection

Vincristine sulfate liposome injection 2.10 mg/m^2

EXPERIMENTAL

Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.

Drug: RituximabDrug: BendamustineDrug: Vincristine sulfate liposome injection

Vincristine sulfate liposome injection 2.14 mg/m^2

EXPERIMENTAL

Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.

Drug: RituximabDrug: BendamustineDrug: Vincristine sulfate liposome injection

Vincristine sulfate liposome injection 2.19 mg/m^2

EXPERIMENTAL

Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.

Drug: RituximabDrug: BendamustineDrug: Vincristine sulfate liposome injection

Vincristine sulfate liposome injection 2.22 mg/m^2

EXPERIMENTAL

Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.

Drug: RituximabDrug: BendamustineDrug: Vincristine sulfate liposome injection

Vincristine sulfate liposome injection 2.24 mg/m^2

EXPERIMENTAL

Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.

Drug: RituximabDrug: BendamustineDrug: Vincristine sulfate liposome injection

Interventions

RituximabDRUG

375 mg/m2 I.V. on Day 1 of each cycle

Also known as: Rituxan, anti-CD20 antibody
Vincristine sulfate liposome injection 1.8 mg/m^2Vincristine sulfate liposome injection 1.95 mg/m^2Vincristine sulfate liposome injection 1.98 mg/m^2Vincristine sulfate liposome injection 2.04 mg/m^2Vincristine sulfate liposome injection 2.10 mg/m^2Vincristine sulfate liposome injection 2.14 mg/m^2Vincristine sulfate liposome injection 2.19 mg/m^2Vincristine sulfate liposome injection 2.22 mg/m^2Vincristine sulfate liposome injection 2.24 mg/m^2
BendamustineDRUG

90 mg/m2 I.V. on Day 1 and 2 of each cycle

Also known as: Treanda
Vincristine sulfate liposome injection 1.8 mg/m^2Vincristine sulfate liposome injection 1.95 mg/m^2Vincristine sulfate liposome injection 1.98 mg/m^2Vincristine sulfate liposome injection 2.04 mg/m^2Vincristine sulfate liposome injection 2.10 mg/m^2Vincristine sulfate liposome injection 2.14 mg/m^2Vincristine sulfate liposome injection 2.19 mg/m^2Vincristine sulfate liposome injection 2.22 mg/m^2Vincristine sulfate liposome injection 2.24 mg/m^2
Vincristine sulfate liposome injectionDRUG

Dose per dose escalation protocol, I.V. on Day 2 of each cycle

Also known as: Marqibo
Vincristine sulfate liposome injection 1.8 mg/m^2Vincristine sulfate liposome injection 1.95 mg/m^2Vincristine sulfate liposome injection 1.98 mg/m^2Vincristine sulfate liposome injection 2.04 mg/m^2Vincristine sulfate liposome injection 2.10 mg/m^2Vincristine sulfate liposome injection 2.14 mg/m^2Vincristine sulfate liposome injection 2.19 mg/m^2Vincristine sulfate liposome injection 2.22 mg/m^2Vincristine sulfate liposome injection 2.24 mg/m^2

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically confirmed indolent B-cell non-Hodgkin lymphoma.
  • Radiological measurable disease.
  • Previous treatment for lymphoma is allowed, with the exception of use of bendamustine within 6 months or any prior use of vincristine sulfate liposome injection
  • Eastern Cooperative Oncology Group performance status 0 or 1;
  • Life expectancy of at least 6 months;
  • Adequate organ and marrow function;
  • Women of child-bearing potential and men must agree to use adequate contraception.
  • Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

  • History of allergic reactions attributed to any drug used in the study.
  • Any lymphoma-directed therapy within 4 weeks.
  • Any prior treatment with vincristine sulfate liposome injection.
  • Prior treatment with bendamustine or vincristine sulfate within 180 days of enrollment.
  • Patients who are receiving any other investigational agents with the exception of endocrine therapy for breast or prostate cancer.
  • Central nervous system involvement.
  • Peripheral sensory or motor neuropathy.
  • History of a demyelinating condition.
  • Positive test for the Human Anti-Chimeric Antibody (HACA).
  • Patients receiving any medications or substances that are strong inhibitors or inducers of Cytochrome P450, family 3, subfamily A (CYP3A) enzyme are ineligible.
  • Uncontrolled intercurrent illness.
  • Prisoners.
  • Pregnant or breast-feeding women.
  • Known Human Immunodeficiency Virus (HIV) or active Hepatitis B infection
  • Any prior or active cancer, which in the opinion of the investigator would preclude safe participation in this study.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Rhode Island Hospital and The Miriam Hospital

Providence, Rhode Island, 02903, United States

Location

Related Publications (1)

  • Ollila T, Butera J, Egan P, Reagan J, Thomas A, Yakirevich I, MacKinnon K, Margolis J, McMahon J, Rosati V, Olszewski AJ. Vincristine Sulfate Liposome Injection with Bendamustine and Rituximab as First-Line Therapy for B-Cell Lymphomas: A Phase I Study. Oncologist. 2022 Jul 5;27(7):532-e542. doi: 10.1093/oncolo/oyab079.

    PMID: 35641232DERIVED

MeSH Terms

Conditions

Lymphoma, Non-HodgkinLymphoma, FollicularLymphoma, Mantle-CellLeukemia, Lymphocytic, Chronic, B-CellWaldenstrom MacroglobulinemiaLymphoma, B-Cell, Marginal Zone

Interventions

RituximabBendamustine HydrochlorideVincristine

Condition Hierarchy (Ancestors)

LymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLeukemia, B-CellLeukemia, LymphoidLeukemiaHematologic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersLymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsButyratesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsBenzimidazolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsVinca AlkaloidsSecologanin Tryptamine AlkaloidsIndole AlkaloidsAlkaloidsIndolesIndolizidinesIndolizines

Results Point of Contact

Title
BrUOG
Organization
Brown University Oncology Research Group
BrUOG@BROWN.EDU
4018633000

Study Officials

  • Adam J Olszewski, MD

    Rhode Island Hospital

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 30, 2014

First Posted

October 6, 2014

Study Start

May 10, 2017

Primary Completion

August 22, 2020

Study Completion

November 18, 2020

Last Updated

February 9, 2023

Results First Posted

February 9, 2023

Record last verified: 2022-05

Data Sharing

IPD Sharing
Will not share

Locations

US(1)