A Phase Ib/II Study of OBINUTUZUMAB Combined to LENALIDOMIDE for the Treatment of Relapsed/Refractory Follicular and Aggressive (DLBCL and MCL) B-cell Lymphoma
Conditions
Follicular Lymphoma Patients (Phase IB) - Follicular and Agressive (DLBCL&MCL) B-cell Lymphoma Patients (Phase II)
Conditions: official terms
Lymphoma - Lymphoma, B-Cell - Lymphoma, Follicular
Study Type
Interventional
Study Phase
Phase 1/Phase 2
Study Design
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Lenalidomide and GA101
Type: Drug
Overall Status
Recruiting
Summary
This study is to determine first the appropriate dose of lenalidomide to administer in combination with fixed doses of obinutuzumab in relapsed/refractory follicular lymphoma patients.

In a second step, this study aims to determine the efficacy of this combiation in 2 separate populations: relapsed/refractory follicular lymphoma in one cohort and relapsed/refractory aggressive lymphoma (diffuse large B-cell lymphoma and mantle cell lymphoma) in the second cohort.
Detailed Description
This study is an open label, multicenter study with two phases:

The Phase IB part of the study is a dose escalation study of lenalidomide (Revlimid) administered orally during on 3 weeks of every 28-day cycle, in combination with fixed doses of obinutuzumab (GA101) in relapsed/refractory follicular lymphoma patients.

The Phase II part of the study is an efficacy study of the association of the recommended dose of lenalidomide associated with GA101 in 2 separate populations of patients: relapsed/refractory follicular lymphoma in one cohort and relapsed/refractory aggressive lymphoma (diffuse large B-cell lymphoma and mantle cell lymphoma) in the second cohort. First, all patients will receive a combination of obinutuzumab and lenalidomide for a total of 6 cycles. Patients who achieve at least a partial response after 6 cycles will receive a maintenance treatment with obinutuzumab for 2 years and Lenalidomide for 1 year as tolerated, or until disease progression.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

- Phase IB only: Histologically documented CD20-positive follicular lymphoma (WHO grade 1, 2, or 3a) patients

- Phase II: Patients with either histologically documented CD20-positive Diffuse large-cell lymphoma or Mantle cell lymphoma (cohort 1) or follicular lymphoma, WHO grade 1, 2 or 3a (cohort 2)

- Phase IB and II:

- Relapsed/refractory NHL after ≥1 prior R-containing regimen with no curative option

- Aged 18 years or more

- ECOG performance status 0, 1 or 2

- At least one bi-dimensionally measurable nodal or tumor lesion defined by CT scan as: greatest transverse diameter > 1.5 cm and a short axis ≥ 10mm

- Signed inform consent

- Life expectancy ≥ 3 months.

- All subjects must be able to understand and fulfill the lenalidomide Pregnancy Prevention Plan requirements (see in appendix)

- Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual contact during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; 3) dose interruptions; and 4) for at least 2 months after discontinuation of all study treatments.

Exclusion Criteria:

- Previous treatment with obinutuzumab or lenalidomide

- Known CD20 negative status at relapse/progression. Biopsy at relapse/progression is recommended but not mandatory

- Central nervous system or meningeal involvement by lymphoma

- Contraindication to any drug contained in the study treatment regimen

- Known HIV or HTLV-1 infection, positive serology to HB surface antigen [HBsAg] or total HB core antibody [anti-HB-c]) and Hepatitis C (Hepatitis C virus [HCV] antibody)

- Any serious active disease or co-morbid medical condition (such as New York Heart Association Class II or IV cardiac disease, severe arrhythmia, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm or other according to investigator's decision)

- Any of the following laboratory abnormalities unless secondary to underlying lymphoma:

- Absolute neutrophil count (ANC) < 1,500 cells/mm3 (1.5 x 109/L).

- Platelet count < 100,000/mm3 (100 x 109/L) unless due to lymphoma for phase II part.

- Serum SGOT/AST or SGPT/ALT 3.0 x upper limit of normal (ULN) unless disease involvement.

- Serum total bilirubin > 2.0 mg/dL (34 μmol/L), except if disease related or in case of Gilbert syndrome

- Calculated creatinine clearance (Cockcroft-Gault formula or MDRD) of < 50 mL /min. For phase II part of the study, patients with calculated creatinine clearance between 30 and 50ml/min can be included and lenalidomide dose will be adjusted as follows (10mg once daily)

- Prior history of malignancies other than lymphoma unless the subject has been free of the disease for ≥ 5 years

- Any serious medical condition, laboratory abnormality (other than mentioned above), or psychiatric illness that would prevent the subject from signing the informed consent form.

- Pregnant or lactating females.

- Prior ≥ Grade 3 allergic reaction/hypersensitivity to thalidomide.

- Prior ≥ Grade 3 rash or any desquamating (blistering) rash while taking thalidomide.

- Subjects with ≥ Grade 2 neuropathy.

- Use of any standard or experimental anti-cancer drug therapy within 28 days of the initiation (Day 1) of study drug therapy

- Patients taking corticosteroids during 4 weeks before inclusion, unless administered at a dose equivalent to ≤ 10 mg/day prednisone (over these 4 weeks)

- Prior history of Progressive Multifocal Leukoencephalopathy (PML)
Locations
ZNA Stuivenberg
Antwerpen, Belgium
Status: Not yet recruiting
Contact: Pierre Zachee, PhD - 0032 32 17 74 87 - pierre.zachee@zna.be
A.Z. Sint Jan AV
Bruges, Belgium
Status: Not yet recruiting
Contact: Achiel Van Hoof, PhD - 0032 50 45 26 27 - Achiel.VanHoof@azsintjan.be
institut Jules Bordet
Bruxelles, Belgium
Status: Not yet recruiting
Contact: Dominique Bron, MD - 0032 25 41 32 12 - ique.bron@bordet.be
Université Catholique de Louvain Saint Luc
Bruxelles, Belgium
Status: Not yet recruiting
Contact: Eric Van den Neste, MD - 0032 27 64 18 00 - eric.vandenneste@uclouvain.be
AZ Groeninge - Campus Maria's Voorzienigheid
Kortrijk, Belgium
Status: Not yet recruiting
Contact: Koenraad Van Eygen, MD - 0032 56 23 45 07 - koen.vaneygen@azgroeninge.be
CHU de Liège
Liège, Belgium
Status: Not yet recruiting
Contact: Christophe Bonnet, MD - 0032 43 66 84 20 - cbonnet@ulg.ac.be
Université Catholique de Louvain Mont Godinne
Yvoir, Belgium
Status: Not yet recruiting
Contact: Marc Andre, PhD - 00 32 81 42 38 64 - marc.andre@uclouvain.be
CHU d'Amiens
Amiens, France
Status: Not yet recruiting
Contact: Jean-Pierre Marolleau, PhD - +333 22 45 59 14 - marolleau.jean-pierre@chu-amiens.fr
Institut Bergonié
Bordeaux, France
Status: Not yet recruiting
Contact: Fontanet Bijou, MD - +335 56 33 32 67 - f.bijou@bordeaux.unicancer.fr
Centre François Baclesse
Caen, France
Status: Recruiting
Contact: Christophe Fruchart, MD - +332 31 45 50 93 - c.fruchart@baclesse.unicancer.fr
CHU d'Estaing
Clermont-Ferrand, France
Status: Not yet recruiting
Contact: Romain Guieze, MD - rguieze@chu-clermontferrand.fr
Hôpital Henri Mondor
Créteil, France
Status: Recruiting
Contact: Corinne Haioun, PhD - +331 49 81 41 54
CHU de Dijon
Dijon, France
Status: Not yet recruiting
Contact: Olivier Casasnovas, PhD - +333 80 29 50 41 - olivier.casasnovas@chu-dijon.fr
CHU de Grenoble
Grenoble, France
Status: Not yet recruiting
Contact: Lysaine Molina, MD - +334 76 76 92 09 - lmolina@chu-grenoble.fr
CHRU de Lille
Lille, France
Status: Recruiting
Contact: Franck Morschhauser, MD - +33 20 44 42 90
Centre Léon Bérard
Lyon, France
Status: Not yet recruiting
Contact: Emmanuelle Nicolas Virelizier, MD - +334 78 78 27 57 - emmanuelle.nicolas@lyon.unicancer.fr
Institut Paoli Calmette
Marseille, France
Status: Not yet recruiting
Contact: Réda Bouabdallah, PhD - +33 491223868 - BOUABDALLAHR@ipc.unicancer.fr
CHU St Eloi
Montpellier, France
Status: Recruiting
Contact: Guillaume Cartron, PhD
CHU Brabois
Nancy, France
Status: Not yet recruiting
Contact: Pierre Feugier, PhD - +333 83 15 32 82 - p.feugier@chu-nancy.fr
CHU Hôtel Dieu
Nantes, France
Status: Recruiting
Contact: Steven Le Gouill, MD - +332 40 08 32 71
Hôpital St Louis
Paris, France
Status: Recruiting
Contact: Catherine Thieblemont, PhD - +331 42 49 92 36
Centre François Magendie
Pessac, France
Status: Recruiting
Contact: Kamal BOUABDALLAH, MD - +335 57 65 65 11
CH Lyon Sud
Pierre Bénite, France
Status: Recruiting
Contact: Gilles Salles, PhD - +334 78 86 43 01
CHU Pontchaillou
Rennes, France
Status: Recruiting
Contact: Roch Houot, MD - +332 99 28 98 73
Centre henri Becquerel
Rouen, France
Status: Recruiting
Contact: Hervé Tilly, PhD - +332 32 08 22 02
Start Date
October 2012
Completion Date
June 2020
Sponsors
The Lymphoma Academic Research Organisation
Source
The Lymphoma Academic Research Organisation
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page