Phase II Study of Vismodegib in Patients With Refractory or Relapsed B-cell Lymphoma or Chronic Lymphocytic Leukemia (VISMOLY)
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|ClinicalTrials.gov Identifier: NCT01944943|
Recruitment Status : Terminated (lack of efficacy)
First Posted : September 18, 2013
Last Update Posted : March 13, 2017
|Condition or disease||Intervention/treatment||Phase|
|Diffuse Large B-cell Lymphoma Indolent Non-hodgkin Lymphoma Primary Central Nervous System Lymphoma Chronic Lymphocytic Leukemia||Drug: Vismodegib||Phase 2|
This is a multicenter open-label phase II study.
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.
- 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).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||31 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of Vismodegib in Patients With Refractory or Relapsed B-cell Lymphoma or Chronic Lymphocytic Leukemia|
|Study Start Date :||February 2013|
|Actual Primary Completion Date :||August 2014|
|Actual Study Completion Date :||October 2014|
Vismodegib 150 mg will be administrated orally at a dosage of 150 mg (1 capsule) once a day during 12 months.
150 mg (1 capsule) of Vismodegib per day orally in continue during 12 months
Other Name: GDC-0449, ERIVEDGE®
- The best overall response rate(ORR) [ Time Frame: 12 months ]
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.
- Overall Response rate [ Time Frame: 2, 4, 6, 9, and 12 months ]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.
- Progression Free Survival (PFS) [ Time Frame: Up to 3 year ]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.
- Response Duration [ Time Frame: Up to 3 year ]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.
- Overall survival [ Time Frame: Up to 3 year ]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.
- Correlation between Hedgehog (Hh) signaling in the tumor and the efficacy of Vismodegib [ Time Frame: At baseline and at 28 days (+/- 7 days) ]
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
- Safety endpoints [ Time Frame: Up to 2 year ]Description of all adverse events (AEs), laboratory data, vital signs and ECOG performance status, performed by cycle/visit and for the entire study.
- Overall Response rate [ Time Frame: 12 months ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01944943
|Hôpital Henri MONDOR|
|Creteil, France, 94010|
|CHU Dijon _ Hôpital d'Enfants|
|Dijon, France, 21000|
|CHRU de Lille _ Hôpital Huriez|
|Lille, France, 59800|
|CHU de Nantes _ Hôtel Dieu|
|Nantes, France, 44093|
|Paris, France, 75475|
|CHU Haut Lévèque|
|Pessac, France, 33604|
|CH Lyon Sud|
|Pierre-Bénite, France, 69495|
|Rennes, France, 35003|
|Centre Henri Becquerel|
|Rouen, France, 76038|
|Hôpital René Huguenin _ Institut Curie|
|Saint-Cloud, France, 92210|
|Principal Investigator:||Roch HOUOT, MD|