NCT01944943

Brief Summary

The purpose of this study is to determine the efficacy of Vismodegib drug in treatment of patients with relapsed or refractory B-cell lymphoma or chronic lymphocytic leukemia (CLL).

Trial Health

57
Monitor

Trial Health Score

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

Enrollment
31

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Feb 2013

Geographic Reach
1 country

10 active sites

Status
terminated

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

Study Start

First participant enrolled

February 1, 2013

Completed
21 days until next milestone

First Submitted

Initial submission to the registry

February 22, 2013

Completed
7 months until next milestone

First Posted

Study publicly available on registry

September 18, 2013

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2014

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2014

Completed
Last Updated

March 13, 2017

Status Verified

March 1, 2017

Enrollment Period

1.5 years

First QC Date

February 22, 2013

Last Update Submit

March 8, 2017

Conditions

Diffuse Large B-cell LymphomaIndolent Non-hodgkin LymphomaPrimary Central Nervous System LymphomaChronic Lymphocytic Leukemia

Keywords

refractory/relapseddiffuse large B-cell lymphomaindolent non-hodgkin lymphomaPrimary central nervous system lymphomachronic lymphocytic leukemia

Outcome Measures

Primary Outcomes (1)

  • The best overall response rate(ORR)

    ORR will be measured by the best overall response (complete response (CR), uncofirmed complete response (CRu) or partial response (PR)) recorded during whole treatment period from the baseline until the end of treatment. ORR will be assessed according to Cheson 1999 for DLBCL and iNHL, according to Abey 2005 (IPCG response criteria) for PCNSL and to Hallek 2008 (IWCLL response criteria) for CLL.

    12 months

Secondary Outcomes (7)

  • Overall Response rate

    2, 4, 6, 9, and 12 months

  • Progression Free Survival (PFS)

    Up to 3 year

  • Response Duration

    Up to 3 year

  • Overall survival

    Up to 3 year

  • Correlation between Hedgehog (Hh) signaling in the tumor and the efficacy of Vismodegib

    At baseline and at 28 days (+/- 7 days)

  • +2 more secondary outcomes

Study Arms (1)

Vismodegib

EXPERIMENTAL

Vismodegib 150 mg will be administrated orally at a dosage of 150 mg (1 capsule) once a day during 12 months.

Drug: Vismodegib

Interventions

VismodegibDRUG

150 mg (1 capsule) of Vismodegib per day orally in continue during 12 months

Also known as: GDC-0449, ERIVEDGE®
Vismodegib

Eligibility Criteria

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

You may qualify if:

  • Histologically confirmed diagnosis of B-cell lymphoma (DLBCL, MCL, FL, MZL, LPL/WM, SLL or PCNSL) or CLL (Matutes score ≥4) requiring treatment that is recurrent after at least one prior therapy for which no potentially curative therapy nor better treatment option is available. Specifically, the patient should have received all treatments considered to be standards of care, including stem cell transplantation (when appropriate, if patient eligible), and agents known to have significant clinical efficacy in their disease.Patient must be eligible for tumor biopsy. Biopsy at relapse is mandatory for all patients except for PCNSL (optional) and should provide enough tumor tissue for biological tests (paraffin-embedded and frozen or RNAlater-conserved tissue).
  • Age 18 and older
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
  • Signed inform consent
  • Life expectancy ≥ 3 months
  • Patients who have received up to a maximum of 4 lines of treatment (including radiotherapy)
  • Patients must have recovered from all toxicities related to prior treatments to ≤ grade 1.
  • Adequate Laboratory Parameters (unless abnormalities are related to underlying disease) within 28 days prior to signing informed consent, including:
  • Absolute neutrophil count (ANC) ≥ 1000/μL
  • Platelet ≥ 75,000/μL
  • Hemoglobin \> 8.5 g/dL
  • Total bilirubin ≤ 1.5 x upper limit of normal (UNL)
  • Hepatic enzymes (AST, ALT) ≤ 3 x institutional ULN
  • Measurable disease:
  • Cohort 1 and 2 (DLBCL and iNHL): Bi-dimensionally measurable disease at CT scan with at least 2cm in their longest diameter.
  • +12 more criteria

You may not qualify if:

  • Pregnant or breastfeeding lactating females.
  • For CLL patients, clinically significant auto-immune cytopenia, Coombs-positive hemolytic anemia as judged by the treating physician
  • Concomitant anti-tumor therapy (e.g., chemotherapy, corticosteroids, other targeted therapy, radiation therapy). Corticosteroids may be authorized for PCNSL only during maximum 3 weeks (before and/or at the beginning of treatment with vismodegib) at a maximum dose of 1mg/kg of prednisone or equivalent.
  • Use of any standard or experimental anti-cancer drug therapy within 28 days prior to the study drug therapy (Day 1).
  • Patients with severe renal failure (creatinine clearance \< 30 ml/min according to Cockcroft \& Gault formula) and/or undergoing dialysis.
  • Note: Patients with moderate renal insufficiency (i.e. creatinine clearance ≥ 30 ml/min) may be included.
  • Uncontrolled and/or unstable concomitant disease such as infection requiring treatment with intravenous antibiotics.
  • HIV positive serology
  • Active hepatitis B or C
  • History of other disease, metabolic dysfunction, physical examination, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the study results or to expose the patient to high risk from treatment complications.
  • Patients unable to comply with the protocol requirements according to the investigator

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Hôpital Henri MONDOR

Créteil, 94010, France

Location

CHU Dijon _ Hôpital d'Enfants

Dijon, 21000, France

Location

CHRU de Lille _ Hôpital Huriez

Lille, 59800, France

Location

CHU de Nantes _ Hôtel Dieu

Nantes, 44093, France

Location

Hôpital Saint-Louis

Paris, 75475, France

Location

CHU Haut Lévèque

Pessac, 33604, France

Location

CH Lyon Sud

Pierre-Bénite, 69495, France

Location

CHU Pontchaillou

Rennes, 35003, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Hôpital René Huguenin _ Institut Curie

Saint-Cloud, 92210, France

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, DiffuseLeukemia, Lymphocytic, Chronic, B-CellRecurrence

Interventions

HhAntag691

Condition Hierarchy (Ancestors)

Lymphoma, B-CellLymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLeukemia, B-CellLeukemia, LymphoidLeukemiaHematologic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Roch HOUOT, MD

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 22, 2013

First Posted

September 18, 2013

Study Start

February 1, 2013

Primary Completion

August 1, 2014

Study Completion

October 1, 2014

Last Updated

March 13, 2017

Record last verified: 2017-03

Locations

FR(10)