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Diffuse Large B-cell LymphomaPhase 2VISMOLYNCT01944943

Phase II Study of Vismodegib in Patients With Refractory or Relapsed B-cell Lymphoma or Chronic Lymphocytic Leukemia

A Phase 2 study testing Vismodegib in people with Diffuse Large B-cell Lymphoma and Indolent Non-hodgkin Lymphoma, run by The Lymphoma Academic Research Organisation at 10 sites in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Vismodegib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
10 sitesFrance
Study dates
Feb 2013to Oct 2014
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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.
  • Cohort 3 (PCNSL): Measurable PCNSL on MRI with gadolinium enhancement (no minimal size) or, for intraocular lymphoma (IOL), measurable disease at fundoscopic examination with elevated level of IL10 (>10 pg/ml) in the acqueous humor.
  • Cohort 4 (CLL): Measurable disease assessable in the blood (lymphocytosis, cytopenia) and/or by imaging (bi-dimensionally measurable disease at CT scan with at least 2cm in their longest diameter)
  • Patient must be able to take oral medication
  • Females of childbearing potential (FCBP) must :
  • have a negative pregnancy test (serum or urine, sensitivity < or = 25IU HCG/L) within 96 hours prior to starting study drug administration.
  • Agree to use two reliable forms of contraception or to practice complete abstinence from heterosexual contact during whole treatment period and up to 7 months after discontinuation of study drug treatment
  • Male patients must agree :
  • to use a condom with female of childbearing potential or to practice complete abstinence during whole treatment period and up to 7 months after discontinuation of study drug treatment.
  • To abstain from donating semen during whole treatment period and up to 7 months after discontinuation of study drug treatment
  • For all patients receiving vismodegib (GDC-0449):
  • To agree to abstain from donating blood during the whole study and for at least 7 months after discontinuation of study drug treatment
  • To agree not to share the study medication with another person

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

France10 sites

  • Hôpital Henri MONDOR

    Créteil, 94010

  • CHU Dijon _ Hôpital d'Enfants

    Dijon, 21000

  • CHRU de Lille _ Hôpital Huriez

    Lille, 59800

  • CHU de Nantes _ Hôtel Dieu

    Nantes, 44093

  • Hôpital Saint-Louis

    Paris, 75475

  • CHU Haut Lévèque

    Pessac, 33604

  • CH Lyon Sud

    Pierre-Bénite, 69495

  • CHU Pontchaillou

    Rennes, 35003

  • Centre Henri Becquerel

    Rouen, 76038

  • Hôpital René Huguenin _ Institut Curie

    Saint-Cloud, 92210

Other trials in France

About this study

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).

Read the detailed description

This is a multicenter open-label phase II study.

Primary objective:

To evaluate the efficacy of vismodegib in patients with relapsed/refractory B-cell lymphoma and CLL as measured by the best overall response rate (ORR) during the treatment period.

Secondary objectives:

  • To evaluate the tolerability and the safety of vismodegib in patients with relapsed/refractory B-cell lymphoma and CLL
  • To evaluate the efficacy of vismodegib in patients with relapsed/refractory B-cell lymphoma and CLL by measuring the overall (OR) and complete response (CR) rate during the study period, the maximum tumor shrinkage, the duration of response, the progression-free survival (PFS) and the overall survival (OS).
  • To examine the expression of GLI-1 and other Hedgehog (Hh) signalling components in the tumor specimens before and during treatment with vismodegib and corresponding efficacy in patients. 44 patients will be included in the study equally distributed into 4 cohorts according to their histological subtype:
  • Cohort 1: 11 patients with Diffuse large B-cell lymphomas (DLBCL)
  • Cohort 2: 11 patients with "indolent" lymphomas (iNHL): Follicular (FL), mantle cell (MCL) and marginal zone lymphoma (MZL) lymphoplasmacytic lymphoma (LPL)/ Waldenstrom macroglobulinemia (WM), small lymphocytic lymphoma (SLL)
  • Cohort 3: 11 patients with Primary central nervous system lymphomas (PCNSL)
  • Cohort 4: 11 patients with Chronic lymphocytic leukemia (CLL).

After 28 days screening period (Baseline), each patient will be treated by Vismodegib 150 mg per os during for a maximum of 12 months until disease progression, unacceptable toxicities, patient consent withdrawal, death, reasons deemed by the treating physician or study termination by the Sponsor.

Tumour assessment (clinical examination, laboratory tests, abdominal and chest CT scan (for PCNSL only at baseline), +/- PET scan for DLBCL, +/- brain MRI and CSF examination and ophthalmic examination for PCNSL, +/- bone marrow examination (except for PCNSL) will be performed at baseline, and then every 2 months during the first 6 months of treatment, and every 3 months thereafter until disease progression or up to 6 months after study treatment stop.

Response to treatment will be assessed also by Pharmacodynamic study in tumor samples by immunohistochimic and qPCR analysis at baseline and after one month of treatment with vismodegib.

Pharmacokinetic studies (before and after 1 month of treatment) will also be performed.

After study treatment discontinuation, the patients will be followed up every 3 months until disease progression or up to 6 months (after 1 year treatement).

Being tested
Vismodegib
Keywords
refractory/relapsed, diffuse large B-cell lymphoma, indolent non-hodgkin lymphoma, Primary central nervous system lymphoma, chronic lymphocytic leukemia
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Leukemia, Lymphocytic, Chronic, B-Cell, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VismodegibDrug

    Also called GDC-0449, ERIVEDGE®

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

Study groups in NCT01944943
Study groupRoleWhat they receive
VismodegibExperimentalVismodegib 150 mg will be administrated orally at a dosage of 150 mg (1 capsule) once a day during 12 months.
Receives: Drug: Vismodegib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 12 months

Secondary outcomes (7)

  1. Overall Response rate

    Overall response rate will be evaluated as ORR, CR, CRu, PR, stable disease (SD) and progressive disease (PD) after 2, 4, 6, 9, and 12 months of treatment and every 3 months for 6 months after treatment discontinuation, until disease progression.

    Measured: 2, 4, 6, 9, and 12 months

  2. Progression Free Survival (PFS)

    Progression-Free Survival will be measured from the date of inclusion to the date of first documented disease progression, relapse or death from any cause. Responding patients and patients who are lost to follow up will be censored at their last tumor assessment date.

    Measured: Up to 3 year

  3. Response Duration

    Duration of response will be measured from the time of attainment of first CR, CRu or PR to the date of first documented disease progression, relapse or death from any cause. Subjects with no documented progression after CR, CRu or PR will be censored at the last tumor assessment date.

    Measured: Up to 3 year

  4. Overall survival

    Overall survival will be measured from the date of inclusion to the date of death from any cause. Alive patients will be censored at their last date known to be alive.

    Measured: Up to 3 year

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

    Hh signaling cascade will be evaluated in tumors at baseline and at the end of cycle 1 (at Day 28 +/- 7 days) in order to:

    • Study pharmacodynamic of the drug (extinction of Hh signaling under treatment with Vismodegib)
    • Search for correlation between Hh signaling and clinical response to Vismodegib

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

  6. Safety endpoints

    Description of all adverse events (AEs), laboratory data, vital signs and ECOG performance status, performed by cycle/visit and for the entire study.

    Measured: Up to 2 year

  7. Overall Response rate

    Overall response will also be assessed using the Cheson 2007 criteria in patients with DLBCL. Patient without response assessment (due to whatever reason) will be considered as non-responder.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Sep 2013 (estimated)
  2. Study startFeb 2013
  3. Primary completionAug 2014
  4. Study completionOct 2014

Why it stopped: lack of efficacy

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01944943
Sponsor's protocol ID
VISMOLY
Acronym
VISMOLY
Status last verified
Mar 2017
First submitted
22 Feb 2013
Last updated
13 Mar 2017
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Vismodegib in people with Diffuse Large B-cell Lymphoma and Indolent Non-hodgkin Lymphoma, run by The Lymphoma Academic Research Organisation at 10 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 13 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: lack of efficacy). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The best overall response rate(ORR) (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01944943.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2017.

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