Study of OBINUTUZUMAB Combined to LENALIDOMIDE for the Treatment of Relapsed/Refractory Follicular and Aggressive B-cell Lymphoma

NCT ID: NCT01582776

Last Updated: 2023-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 317 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-03
• Study Completion Date: 2022-05-20

Brief 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 combination in 3 separate populations: relapsed/refractory aggressive lymphoma (diffuse large B-cell lymphoma and mantle cell lymphoma: cohort 1), relapsed/refractory follicular lymphoma (cohort 2) and previously untreated follicular lymphoma (cohorts 3 and 4).

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 aggressive lymphoma (diffuse large B-cell lymphoma and mantle cell lymphoma: cohort 1), relapsed/refractory follicular lymphoma (cohort 2) and previously untreated follicular lymphoma (cohorts 3 and 4). 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.

Conditions

Follicular Lymphoma Patients (Phase IB); Follicular and Agressive (DLBCL&MCL) B-cell Lymphoma Patients (Phase II)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lenalidomide and GA101

Ga101 and lenalidomide

Group Type: EXPERIMENTAL

Lenalidomide and GA101

Intervention Type: DRUG

1000mg of GA101 on D8, D15 and D22of cycle 1 and on D1 of cycles 2 to 6. Oral lenalidomide once daily at 10/15/20/25mg (phase I part) or at recommended dose (phase II part) on days 1 to 21 of a 28-day cycle for the first cycle and on days 2 to 22 of a 28-day cycle for cycles 2 to 6.

Interventions

Lenalidomide and GA101

1000mg of GA101 on D8, D15 and D22of cycle 1 and on D1 of cycles 2 to 6. Oral lenalidomide once daily at 10/15/20/25mg (phase I part) or at recommended dose (phase II part) on days 1 to 21 of a 28-day cycle for the first cycle and on days 2 to 22 of a 28-day cycle for cycles 2 to 6.

Intervention Type: DRUG

Other Intervention Names

Revlimid; Obinutuzumab

Eligibility 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 2-3-4)
• Phase IB and II:
• Relapsed/refractory NHL after ≥1 prior R-containing regimen with no curative option (cohort 2 only)
• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Lymphoma Academic Research Organisation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Franck MORSCHHAUSER, Professor

Role: PRINCIPAL_INVESTIGATOR

Lymphoma Study Association

Roch HOUOT, Professor

Role: PRINCIPAL_INVESTIGATOR

Lymphoma Study Association

Locations

ZNA Stuivenberg

Antwerp, , Belgium

A.Z. Sint Jan AV

Bruges, , Belgium

institut Jules Bordet

Brussels, , Belgium

Université Catholique de Louvain Saint Luc

Brussels, , Belgium

AZ Groeninge - Campus Maria's Voorzienigheid

Kortrijk, , Belgium

CHU de Liège

Liège, , Belgium

Université Catholique de Louvain Mont Godinne

Yvoir, , Belgium

CHU d'Amiens

Amiens, , France

Institut Bergonié

Bordeaux, , France

Institut d'Hématologie de Basse Normandie

Caen, , France

CHU d'Estaing

Clermont-Ferrand, , France

Hôpital Henri Mondor

Créteil, , France

CHU de Dijon

Dijon, , France

CHU de Grenoble

Grenoble, , France

CHRU de Lille

Lille, , France

Centre Léon Bérard

Lyon, , France

Institut Paoli Calmette

Marseille, , France

CHU St Eloi

Montpellier, , France

CHU Brabois

Nancy, , France

CHU Hôtel Dieu

Nantes, , France

Hôpital St Louis

Paris, , France

Centre François Magendie

Pessac, , France

CH Lyon Sud

Pierre-Bénite, , France

CHU Pontchaillou

Rennes, , France

Centre henri Becquerel

Rouen, , France

Countries

Belgium; France

References

Bachy E, Houot R, Feugier P, Bouabdallah K, Bouabdallah R, Virelizier EN, Maerevoet M, Fruchart C, Snauwaert S, Le Gouill S, Marolleau JP, Molina L, Molucon-Chabrot C, Thieblemont C, Tilly H, Bijou F, Haioun C, Van den Neste E, Fabiani B, Meignan M, Cartron G, Salles G, Casasnovas O, Morschhauser F. Obinutuzumab plus lenalidomide in advanced, previously untreated follicular lymphoma in need of systemic therapy: a LYSA study. Blood. 2022 Apr 14;139(15):2338-2346. doi: 10.1182/blood.2021013526.

Reference Type: DERIVED

PMID: 34936697 (View on PubMed)

Morschhauser F, Le Gouill S, Feugier P, Bailly S, Nicolas-Virelizier E, Bijou F, Salles GA, Tilly H, Fruchart C, Van Eygen K, Snauwaert S, Bonnet C, Haioun C, Thieblemont C, Bouabdallah R, Wu KL, Canioni D, Meignin V, Cartron G, Houot R. Obinutuzumab combined with lenalidomide for relapsed or refractory follicular B-cell lymphoma (GALEN): a multicentre, single-arm, phase 2 study. Lancet Haematol. 2019 Aug;6(8):e429-e437. doi: 10.1016/S2352-3026(19)30089-4. Epub 2019 Jul 8.

Reference Type: DERIVED

PMID: 31296423 (View on PubMed)

Morschhauser F, Salles G, Le Gouill S, Tilly H, Thieblemont C, Bouabdallah K, Fabiani B, Menard C, Tarte K, Cartron G, Houot R. An open-label phase 1b study of obinutuzumab plus lenalidomide in relapsed/refractory follicular B-cell lymphoma. Blood. 2018 Oct 4;132(14):1486-1494. doi: 10.1182/blood-2018-05-853499. Epub 2018 Aug 1.

Reference Type: DERIVED

PMID: 30068505 (View on PubMed)

Related Links

http://www.lysa-lymphoma.org/

Lymphoma Study Association

Other Identifiers

GALEN

Identifier Type: -

Identifier Source: org_study_id